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Health benefits of Kombucha: drink and its biocellulose production

Abstract

Kombucha (tea and biocelluose) has been used worldwide due to its high nutritional, functional, and economic potential. This fermented tea has been used in folk medicine to treat several pathological conditions and its biocellulose in the industrial sector. In this context, this paper presents a scientific literature review on the main phytochemicals of Kombucha and respective biological activities to assess their potential uses. The tea has presented a wide range of bioactive compounds such as amino acids, anions, flavonoids, minerals, polyphenols, vitamins, and microorganisms. Moreover, its biocellulose is rich in fibers. These compounds contribute to various biological responses such as antioxidant, hepatoprotective, antitumoral, antidiabetic, and antihypercholesterolemic effects. In this sense, both the tea and its biocellulose are promising for human use. Besides, Kombucha presents itself as a drink option for vegetarians and/or those seeking healthier diets, as its biocellulose can bring metabolic benefits. Our review demonstrates that both can be used as functional foods and/or sources of bioactive compounds for food and industrial applications.

Keywords:
Kombucha; Fermentation; Tea; Biocellulose; Polyphenols

INTRODUCTION

Human consumption of fermented milk dates from about 10.000 years ago. Fermentation has been used for alcohol production from grains, fruits, and beetroots. In the excavation of the tomb of an Egyptian pharaoh in 1995, papyri were found describing a liquor to treat diseases, which consisted of a combination of wine and herbs. Wine was the first fermented beverage according to Arnaldus de Villa Nova, in books of the XVI century, besides being described as a medicinal drink to treat dementia and sinusitis (Ozen, Dinleyici, 2015Ozen M, Dinleyici EC. The history of probiotics: the untold story. Benefic Microbes. 2015;6(2):159-65.).

Every food has its own importance to human metabolism whether as a source of energy, nutrients, or bioactive compounds (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Functional foods promote beneficial effects on one or more human organism functions and ensure bodily health and well-being. Kombucha is a functional beverage produced from a symbiosis of bacteria and yeasts, whose metabolisms are interdependent and with mutual benefits (Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.). The microorganisms in this beverage can become part of the intestinal flora of those who drink it (Shi et al., 2016Shi LH, Balakrishnan K, Thiagarajah K, Ismail NIM, Yin OS. Beneficial properties of probiotics. Trop Life Sci Res. 2016;27(2):73-90.; Amarasinghe, Weerakkody, Waisundara, 2018Amarasinghe H, Weerakkody NS, Waisundara VY. Evaluation of physicochemical properties and antioxidant activities of kombucha “Tea Fungus” during extended periods of fermentation. Food Sci Nutr. 2018;6(3):659-65.). Kombucha or fungus tea (Chen, Liu, 2000Chen C, Liu BY. Changes in major components of tea fungus metabolites during prolonged fermentation. J Appl Microbiol. 2000;89(5):834-9.) is the name of a carbonated beverage consumed worldwide, which has a slightly sweet and citrusy taste, with low alcohol content and vinegar-like taste. The term “Kombucha” derives from the Japanese words kombu (seaweed) and cha (tea) (Ernst, 2003Ernst E. Kombucha: A systemic review of the clinical evidence. Forsch Komplementarmed Klass Naturheilkd. 2003;10(2):85-7.). It is also popularly known as Chainii grib, Chainii kvass, Champignon de longue vie, Kocha kinoko, Ling zhi, and Red tea fungus (Amarasinghe, Weerakkody, Waisundara, 2018Amarasinghe H, Weerakkody NS, Waisundara VY. Evaluation of physicochemical properties and antioxidant activities of kombucha “Tea Fungus” during extended periods of fermentation. Food Sci Nutr. 2018;6(3):659-65.).

The term probiotic refers to living microorganisms that promote nutritional benefits. Some bacteria and yeasts are used in beverage production (acetic and alcoholic) and foods such as sauerkraut, yogurts, and dairy drinks (Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.). Fermented foods have beneficial effects on human cognition, intestinal flora composition, and the immune system. They also have anti-allergic, anti-atherosclerosis, and anti-inflammatory effects, besides being used in the treatment of cancer, diabetes mellitus, and hypertension (Bellassoued et al., 2015Bellassoued K, Ghrab F, Makni-Ayadi F, Pelt JV, Elfeki A, Ammar E. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity. Pharm Biol. 2015;53(11):1699-709.; Marco et al., 2017Marco ML, Heeney D, Binda S, Cifelli CJ, Cotter PD, Foligné B, et al. Health benefits of fermented foods: microbiota and beyond. Curr Opin Biotechnol. 2017;44:94-102.; Şanlier et al., 2019Şanlier N, Gökcen BB, Sezgin AC. Health benefits of fermented foods. Crit Rev Food Sci Nutr . 2019;59(3):506-27.; Xia et al., 2019Xia X, Dai Y, Wu H, Liu X, Wang Y, Yin L, et al. Kombucha fermentation enhances the health-promoting properties of soymilk beverage. J Funct Foods . 2019;62:103549.). In turn, prebiotics are chemical compounds metabolized by the gut microbiota (e.g., fructooligosaccharides, and galactooligosaccharides) (Davani-Davari et al., 2019Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, et al. Prebiotics: definition, types, sources, mechanisms, and clinical applications. Foods. 2019;8(3):92.), which bring benefits to human health. Symbiotic foods contain probiotic microorganisms and prebiotic nutrients. Their intake increases microbial survival after passing through the gastrointestinal tract and then be incorporated into the human microbiome (Pandey, Naik, Vakil, 2015Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics - a review. J Food Sci Technol . 2015;52(12):7577-87.; Markowiak, Śliżewska, 2017Markowiak P, Śliżewska K. Effects of probiotics, prebiotics, and synbiotics on human health. Nutrients . 2017;9(9):1-30.)..

Kombucha is believed to originate from Manchuria, northeastern China (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Goh et al., 2012 Goh WN, Rosma A, Kaur B, Fazilah A, Karim AA, Rajeev B. Fermentation of black tea broth (Kombucha): I. Effects of sucrose concentration and fermentation time on the yield of microbial cellulose. Int Food Res J. 2012;19(1):109-17.; Salafzoon, Hosseini, Halabian, 2017Salafzoon S, Hosseini HM, Halabian R. Evaluation of the antioxidant impact of ginger-based kombucha on the murine breast cancer model. J Complement Integr Med. 2017;15(1) doi: 10.1515/jcim-2017-0071.
https://doi.org/10.1515/jcim-2017-0071....
), during the Jin Dynasty (220 BC) (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.; Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.). After spreading to countries near China, its use became common and disseminated due to trade routes and globalization. It became popular after World War II and gained the interest of consumers and beverage companies. In 2016, PepsiCo bought the company Kevita, a Kombucha producer; then, in 2017, its consumption and of other fermented drinks increased by 37.4%. In 2018, its sales grew by 49 million dollars due to its commercial rise (Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.). This beverage is mainly consumed in Asian countries, but it has gained popularity in other parts of the world (Pakravan et al., 2018Pakravan N, Mahmoudi E, Hashemi S-A, Kamali J, Hajiaghayi R, Rahimzadeh M, et al. Cosmeceutical effect of ethyl acetate fraction of kombucha tea by intradermal administration in the skin of aged mice. J Cosmet Dermatol. 2018;17(6):1216-24.).

In Russia, Kombucha is used to treat metabolic diseases, hemorrhoids, and rheumatisms, whereas in Europe for digestive system improvement and blood detoxification (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.). Studies have shown that such a drink can mitigate diabetes mellitus, dyslipidemia, and non-alcoholic liver sclerosis, as well as decrease the action of free radicals and act against enteric parasites and scalp fungi (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Aloulou et al., 2012Aloulou A, Hamden K, Elloumi D, Ali MB, Hargafi K, Jaouadi B, et al. Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats. BMC Complementary Altern Med. 2012;12:63.; Bellassoued et al., 2015Bellassoued K, Ghrab F, Makni-Ayadi F, Pelt JV, Elfeki A, Ammar E. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity. Pharm Biol. 2015;53(11):1699-709.; Mahmoudi et al., 2016Mahmoudi E, Saeidi M, Marashi MA, Moafi A, Mahmoodi V, Zeinolabedini ZM. In vitro activity of kombucha tea ethyl acetate fraction against Malassezia species isolated from seborrhoeic dermatitis. Curr Med Mycol. 2016;2(4):30-6.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.; Dimidi et al., 2019Dimidi E, Cox SR, Rossi M, Whelan K. Fermented foods: definitions and characteristics, impact on the gut microbiota and effects on gastrointestinal health and disease. Nutrients. 2019;11(8):1806.; Jung et al., 2019Jung Y, Kim I, Mannaa M, Kim J, Wang S, Park I, et al. Effect of Kombucha on gut-microbiota in mouse having non-alcoholic fatty liver disease. Food Sci Biotechnol . 2019;28(1):261-7.; Xia et al., 2019Xia X, Dai Y, Wu H, Liu X, Wang Y, Yin L, et al. Kombucha fermentation enhances the health-promoting properties of soymilk beverage. J Funct Foods . 2019;62:103549.).

Given the great diversity of eating habits and advances in food and health technologies, several dietary patterns have emerged, among them vegetarianism with emphasis on veganism. This aims to reduce animal suffering, meat consumption, and some environmental problems related to animal protein production (Key, Appleby, Rosell, 2006Key TJ, Appleby PN, Rosell MS. Health effects of vegetarian and vegan diets. Proc Nutr Soc . 2006;65(1):35-41.; Le, Sabaté, 2014Le LT, Sabaté J. Beyond meatless, the health effects of vegan diets: findings from the Adventist cohorts. Nutrients . 2014;6(6):2131-47.; Appleby, Key, 2016Appleby PN, Key TJ. The long-term health of vegetarians and vegans. Proc Nutr Soc. 2016;75(3):287-93.). Thus, tea and biocellulose from Kombucha can be suitable not only for vegetarians but also for those who seek a quality of life by preventing and treating diseases.

This review proposes to describe the benefits of Kombucha regarding the effects of symbiotic fermentation on body metabolism and its biocellulose.

FROM KOMBUCHA PREPARATION TO DISEASE TREATMENT

Kombucha can be made at home using sterilized utensils and good quality water to avoid contamination by pathogenic microorganisms (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.). It is prepared from an infusion of herbs (5 g of a chosen herb per liter of water) and addition of sugar for fermentation (from 50 to 200 g/L) (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Black tea (Camelia sinensis) is the most used infusion since it has high concentrations of antioxidant compounds after fermentation (Cardoso et al., 2020Cardoso RR, Oliveira Neto R, D’Almeida CTS, Nascimento TP, Pressete CG, Azevedo L, et al. Kombuchas from green and black teas have different phenolic profile, which impacts their antioxidant capacities, antibacterial and antiproliferative activities. Food Res Int. 2020;128:108782.). Green tea, meanwhile, stands out for its antibiotic functions (Primiani et al., 2018Primiani CN, Pujiati P, Mumtahanah M, Ardhi W. Kombucha fermentation test used for various types of herbal teas. J Phys Conf Ser. 2018;1025(1):1-9.; Cardoso et al., 2020Cardoso RR, Oliveira Neto R, D’Almeida CTS, Nascimento TP, Pressete CG, Azevedo L, et al. Kombuchas from green and black teas have different phenolic profile, which impacts their antioxidant capacities, antibacterial and antiproliferative activities. Food Res Int. 2020;128:108782.). Other substrates used are mint, jasmine, lemongrass teas (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.), oolong (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.), rooibos (Gaggìa et al., 2019Gaggìa F, Baffoni L, Galiano M, Nielsen DS, Jakobsen RR, Castro-Mejía JL, et al. Kombucha beverage from green, black and rooibos teas: a comparative study looking at microbiology, chemistry and antioxidant activity. Nutrients. 2019;11(1):1. doi: 10.3390/nu11010001.
https://doi.org/10.3390/nu11010001....
), and coconut water (Watawana et al., 2016Watawana MI, Jayawardena N, Gunawardhana CB, Waisundara VY. Enhancement of the antioxidant and starch hydrolase inhibitory activities of king coconut water (Cocos nucifera var. aurantiaca) by fermentation with kombucha ‘tea fungus’. Int J Food Sci Tech. 2016;51(2):490-8.). Herbal teas of mint, lime flower, and barley have been tested but have not obtained good fermentation results nor the same compounds as in Kombucha using Camelia sinensis (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.). After 10 minutes boiling in water with sugar, tea leaves can be removed, letting the drink cool down to introduce the microbial colony (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.), whose microorganisms are called SCOBY (Symbiotic Culture of Bacteria and Yeast), which vary with the season and geographical region (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.).

The most common SCOBY bacteria are Acetobacter aceti, Acetobacter pasteurianus, Acetobacter xylinoides, Acetobacter xylinum, Bacterium gluconicum, Enterococcus sp, Gluconobacter oxydans, Lactobacillus sp., Lactococcus sp., Leuconostoc sp., Propionilbacterium sp., and Spacobum. Yet the main yeasts are Brettanomyces bruxellensis, Brettanomyces lambicus, Saccharomyces cerevisiae, Saccharomyces ludwigii, Schizosaccharomyces pombe, Zygosaccharomyces bailii, Zygosaccharomyces rouxii, and Torulaspora delbrueckii (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Goh et al., 2012 Goh WN, Rosma A, Kaur B, Fazilah A, Karim AA, Rajeev B. Fermentation of black tea broth (Kombucha): I. Effects of sucrose concentration and fermentation time on the yield of microbial cellulose. Int Food Res J. 2012;19(1):109-17.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.).

During fermentation, Kombucha drink pH must be 2.5 (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.). Yet the final pH should be 4.2 to avoid a high concentration of acetic acid (Kovacevic et al., 2014Kovacevic Z, Davidovic G, Vuckovic-Filipovic J, Janicijevic-Petrovic MA, Janicijevic K, Popovic A. A toxic hepatitis caused the kombucha tea - case report. Open Access Maced J Med Sci. 2014;2(1):128-31.), as it acidifies the beverage and produces a vinegar odor (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Sucrose fermentation was reported to produce 11 g/L acetic acid on the 30th day, which decreases to 8 g/L on the 60th day (Chen, Liu, 2000Chen C, Liu BY. Changes in major components of tea fungus metabolites during prolonged fermentation. J Appl Microbiol. 2000;89(5):834-9.). However, this amount is smaller when molasses is fermented (Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.).

Kombucha beverage is commercially prepared by adding preservatives such as sodium benzoate (0.1%) and potassium sorbate (0.1%), and then maintained under refrigeration (Watawana et al., 2015Watawana MI, Jayawardena N, Gunawardhana CB, Waisundara VY. Health, wellness, and safety aspects of the consumption of kombucha. J Chem. 2015;1:1-11.).

Villarreal-Soto et al. (2019Villarreal-Soto SA, Beaufort S, Bouajila J, Souchard J-P, Renard T, Rollan S, et al. Impact of fermentation conditions on the production of bioactive compounds with anticancer, anti-inflammatory and antioxidant properties in kombucha tea extracts. Process Biochem. 2019;83:44-54.) fermented Kombucha for 21 days in two 1.15-cm-high containers (9- and 23-cm diameter, respectively) and identified 47 different compounds (e.g., alcohols, sugars, and phenols). They also noted that the larger container had higher concentrations of anti-inflammatory molecules. Therefore, the larger the fermentation containers, the greater the quantity and the final effect of chemical compounds produced.

Fermented Kombucha is usually stored for 3 to 10 days (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). This period can last up to 60 days, depending on the culture of bacteria or yeasts (Watawana et al., 2015Watawana MI, Jayawardena N, Gunawardhana CB, Waisundara VY. Health, wellness, and safety aspects of the consumption of kombucha. J Chem. 2015;1:1-11.). At longer fermentation times, storage temperature should be close to 30 °C, as lower temperatures may decrease counts of yeasts and of acetic and lactic bacteria (Fu et al., 2014Fu C, Yan F, Cao Z, Xie F, Lin J. Antioxidant activities of kombucha prepared from three different substrates and changes in content of probiotics during storage. Food Sci Technol. 2014;34(1):123-6.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Moreover, fermentation containers must be covered with a cloth or other porous media to allow gas exchange, as microbial colonies perform anaerobic respiration and thus produce gases (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.). After fermentation, the fermented tea or just a biocellulose film can be added to another infusion to form a new drink and new biocellulose films (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.). Amarasinghe, Weerakkody, Waisundara (2018Amarasinghe H, Weerakkody NS, Waisundara VY. Evaluation of physicochemical properties and antioxidant activities of kombucha “Tea Fungus” during extended periods of fermentation. Food Sci Nutr. 2018;6(3):659-65.) reported that a 2-month fermentation decreases beverage antioxidant activity and increases its acidity and turbidity, thus changing its sensory properties. Thus, the tea must be consumed before such period so that its bioactive compounds could bring benefits to consumers.

SCOBY metabolism

Biochemically, fermentation is a metabolic process of obtaining energy from the SCOBY microorganisms in Kombucha. This process is influenced by storage-room temperature, fermentation time, and sucrose content (Goh et al., 2012 Goh WN, Rosma A, Kaur B, Fazilah A, Karim AA, Rajeev B. Fermentation of black tea broth (Kombucha): I. Effects of sucrose concentration and fermentation time on the yield of microbial cellulose. Int Food Res J. 2012;19(1):109-17.; Fu et al., 2014Fu C, Yan F, Cao Z, Xie F, Lin J. Antioxidant activities of kombucha prepared from three different substrates and changes in content of probiotics during storage. Food Sci Technol. 2014;34(1):123-6.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Yeasts (Brettanomyces, Candida, Pichia, Saccharomyces, Saccharomycodes, and Zygosaccharomyces) (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.) produce the enzyme invertase, which catalyzes the hydrolysis of sucrose into glucose and fructose (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.). These, in turn, are substrates used by Kombucha bacteria and yeasts to produce ethanol and carbon dioxide (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.; May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.; Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.). The main bacterial genera in the SCOBY are Acetobacter and Gluconobacter. From the actions of alcohol dehydrogenase and aldehyde dehydrogenase, Acetobacter transform ethanol into acetic acid, which reduces the pH of the beverage (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.), and enters the Krebs Cycle, producing CO2, H2O, NADH, FADH2, ATP, and other compounds (Bellassoued et al., 2015Bellassoued K, Ghrab F, Makni-Ayadi F, Pelt JV, Elfeki A, Ammar E. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity. Pharm Biol. 2015;53(11):1699-709.).

The acetic acid produced during Kombucha fermentation has antibacterial activity and prevents beverage contamination with pathogenic bacteria (Watawana et al., 2015Watawana MI, Jayawardena N, Gunawardhana CB, Waisundara VY. Health, wellness, and safety aspects of the consumption of kombucha. J Chem. 2015;1:1-11.). High ethanol levels in tea can alter cell membranes of bacteria and yeasts, decreasing their concentrations (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.). Some phenolic compounds in tea infusions are degraded by enzymes and increase contents of antioxidant molecules in drinks (Bellassoued et al., 2015Bellassoued K, Ghrab F, Makni-Ayadi F, Pelt JV, Elfeki A, Ammar E. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity. Pharm Biol. 2015;53(11):1699-709.). Bacteria in tea drinks transform fructose and glucose into gluconic acid and cellulose, which will compose biocellulose or biofilm (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.).

Importance of bacterial biocellulose

Polymers are divided into three groups: biopolymers, synthetic polymers, and bioengineering polymers. Cellulose produced by microorganisms is known as biocellulose and is 100% biodegradable. It stands out for its fiber size and purity of 99%, while plant-produced cellulose has only 80% (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.). This is because bacterial cellulose does not have impurities such as hemicellulose, lignin, and pectin (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.; Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.).

When using sucrose, Acetobacter xylinum bacteria ferment part of the sugar and produce a floating cellulose membrane as a secondary metabolite (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.), which is known as biofilm or bacterial biocellulose (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.). The bacterial genera Acetobacter, Agrobacterium, Erwinia, Gluconacetobacter, Komagataeibacter, and Pseudomonas synthesize cellulose. Acetobacter produce higher amounts of extracellular cellulose in form of pure microfibers from carbon sources such as fructose, glucose, sucrose, and ethanol. Whereas the genera Gluconacetobacter and Komagataeibacter do not produce satisfactory amounts of cellulose (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.).

Macroscopically, biocellulose is a light brown gelatinous multilayered membrane. It is gelatinous when kept at rest, but when stirred, it forms irregular masses accumulated in dispersed suspension such as granule, stellate, and fibrous strand (El-Saied, Basta, Gobran, 2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.). Microscopically, filaments with diameters below 100 nm until 30 μm emerging from bacterial pores can be observed (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.). The 1,4 β-glucans chains of cellulose are strongly assembled by hydrogen bonds have a high degree of crystallinity, and good mechanical strength (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.).

Although the main carbon source for biocellulose formation by Acetobacter xylinum or Gluconacetobacter xylinus is glucose, other molecules can also be used such as monosaccharides (e.g., D-fructose, D-galactose, D-glucose, D-mannose, D-xylose, L-arabinosis, and L-sorbose), disaccharides (e.g., cellobiose, lactose, maltose, and sucrose), oligosaccharides (e.g., starch), alcohol (e.g., diethylene glycol, ethanol, ethylene glycol, glycerol, myoinositol, propylene glycol, D-arabitol, and D-mannitol), and acids (e.g., citrate, L-malate, and succinate). Among the monosaccharides, galactose and xylose provide less biocellulose growth (El-Saied, Basta, Gobran, 2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.).

Microorganisms must have carbon and nitrogen sources to produce biocellulose. This is because its formation is complex and involves several enzymes and regulatory proteins (Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.). The first step is the intracellular formation of 1,4 β-glucans chains through phosphorylation of glucose by glucokinase, isomerization of glucose-6P to glucose-1P by phosphoglycutase, synthesis of uridine diphosphate (UDP-glucose) by UDP-glucose phosphorylase, and cellulose synthesis by cellulose synthase (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.). In the second step, cellulose chains will be released from cells to assemble fibers, which undergo crystallization (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.; Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.). In Acetobacter xylinum, cellulose synthase is a membrane-anchored protein (molecular mass of 400-500 kDa), which releases cellulose fibers in form of 1,4 β-glucans (El-Saied, Basta, Gobran, 2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.).

Biocellulose starts its macroscopic formation from a thin layer of cellulose filaments, 2 days after bacterial incubation (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.). Such structure works as protection mechanisms for microorganisms (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.) against UV light effects, as well as keeps bacteria and yeasts closer to the medium surface, wherein oxygen supply is adequate (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.; May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.). The thin layers overlap to form a structure like pastry dough (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.).

Gases from yeast alcoholic fermentation allow biocellulose sheets to f loat to the drink surface (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.). In several bacteria and yeasts, remaining cellulose microfibrils make up biocellulose (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Villarreal-Soto et al., 2019Villarreal-Soto SA, Beaufort S, Bouajila J, Souchard J-P, Renard T, Rollan S, et al. Impact of fermentation conditions on the production of bioactive compounds with anticancer, anti-inflammatory and antioxidant properties in kombucha tea extracts. Process Biochem. 2019;83:44-54.). The association among antimicrobial metabolites, low pH, and biocellulose inhibits the growth of competing microorganisms in Kombucha (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.). In vitro and in vivo studies have suggested that probiotics (Lactobacillus and Saccharomyces) have an anti-Helicobacter pylori effect, which helps in curing gastritis and ulcers (Nair et al., 2016Nair MRB, Chouhan D, Gupta SS, Chattopadhyay S. Fermented foods: are they tasty medicines for Helicobacter pylori associated peptic ulcer and gastric cancer? Front Microbiol. 2016;7:1148.). However, Kombucha has a low pH, so it should be used moderately.

Biocellulose production may vary from 1.76 to 15.3 g/L, which depends on the microbial genera and sources of carbon and nitrogen used (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.). Kombucha has a great potential for biocellulose production, wherein 10.8 ± 0.5 g/L cellulose can be obtained using a black tea with 100 g/L sucrose (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.). Figure 1 shows images from preparation to the consumption of Kombucha tea.

FIGURE 1
Kombucha from preparation to consumption. A - black tea preparation (water, sugar, and dehydrated leaves of Camellia sinensis); B - SCOBY colony addition; C - biocellulose floating in kombucha; D - ready-to-drink kombucha (acid and citrus-flavored beverage in the glass cup, and slightly acid and sweet-flavored beverage in the jug).

Kombucha composition

Kombucha consumption benefits come from its amounts of organic and inorganic compounds, which may vary with the herb chosen for infusion (Salafzoon, Hosseini, Halabian, 2017Salafzoon S, Hosseini HM, Halabian R. Evaluation of the antioxidant impact of ginger-based kombucha on the murine breast cancer model. J Complement Integr Med. 2017;15(1) doi: 10.1515/jcim-2017-0071.
https://doi.org/10.1515/jcim-2017-0071....
; Shahbazi et al., 2018Shahbazi H, Gahruie HH, Golmakani M-T, Eskandari MH, Movahedi M. Effect of medicinal plant type and concentration on physicochemical, antioxidant, antimicrobial, and sensorial properties of kombucha.Food Sci Nutr . 2018;6(8):2568-77.).

Kombucha beverage is a cocktail of chemical components (Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.), including probiotics (Fu et al., 2014Fu C, Yan F, Cao Z, Xie F, Lin J. Antioxidant activities of kombucha prepared from three different substrates and changes in content of probiotics during storage. Food Sci Technol. 2014;34(1):123-6.; Bogdan et al., 2018Bogdan M, Justine S, Filofteia DC, Petruţa CC, Gabriela L, Roxana UE, et al. Lactic acid bacteria strains isolated from Kombucha with potential probiotic effect. Rom Biotech Lett. 2018;23(3):13592-8.), acids (e.g., acetic, citric, gluconic, lactic, malic, malonic, oxalic, pyruvic, saccharic, succinic, and tartaric) (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.; Ivanišová et al., 2020Ivanišová E, Meňhartová K, Terentjeva M, Harangozo Ľ, Kántor A, Kačániová M. The evaluation of chemical, antioxidant, antimicrobial and sensory properties of kombucha tea beverage. J Food Sci Technol . 2020;57(5):1840-6.), essential amino acids (e.g., isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine), non-essential amino acids (e.g., alanine, aspartic acid, cysteine, glycine, glutamic acid, proline, and tyrosine), caffeine (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Goh et al., 2012 Goh WN, Rosma A, Kaur B, Fazilah A, Karim AA, Rajeev B. Fermentation of black tea broth (Kombucha): I. Effects of sucrose concentration and fermentation time on the yield of microbial cellulose. Int Food Res J. 2012;19(1):109-17.), vitamins (e.g., B1, B2, B6, B12, and C), purines, hydrolytic enzymes, biogenic amines, fibers, ethanol (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.), minerals (e.g., cadmium, chromium, cobalt, iron, manganese, nickel, potassium, and zinc), anions (e.g., bromide, chloride, floret, iodide, nitrate, phosphate, and sulfate) (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.; Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.; Xia et al., 2019Xia X, Dai Y, Wu H, Liu X, Wang Y, Yin L, et al. Kombucha fermentation enhances the health-promoting properties of soymilk beverage. J Funct Foods . 2019;62:103549.), polyphenols (e.g., epicatechin, epicatechin gallates, and epigallocatechin) (Shahbazi et al., 2018Shahbazi H, Gahruie HH, Golmakani M-T, Eskandari MH, Movahedi M. Effect of medicinal plant type and concentration on physicochemical, antioxidant, antimicrobial, and sensorial properties of kombucha.Food Sci Nutr . 2018;6(8):2568-77.), and flavonoids (Pakravan et al., 2018Pakravan N, Mahmoudi E, Hashemi S-A, Kamali J, Hajiaghayi R, Rahimzadeh M, et al. Cosmeceutical effect of ethyl acetate fraction of kombucha tea by intradermal administration in the skin of aged mice. J Cosmet Dermatol. 2018;17(6):1216-24.; Jakubczyk et al., 2020Jakubczyk K, Kałduńska J, Kochman J, Janda K. Chemical profile and antioxidant activity of the kombucha beverage derived from white, green, black and red tea. Antioxidants. 2020;9(5):447. doi: 10.3390/antiox9050447.
https://doi.org/10.3390/antiox9050447....
).

The ethanol content in Kombucha ranges from 3.6 to 10 g/L (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.). The alcohol content produced by bacteria and yeasts is proportional to fermentation time and reach 5.5 g/L on the 20th day (Chen, Liu, 2000Chen C, Liu BY. Changes in major components of tea fungus metabolites during prolonged fermentation. J Appl Microbiol. 2000;89(5):834-9.). However, this content must not exceed 10 g ethanol/liter of drink to prevent invasion by competing microorganisms (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.).

Toxicity

Despite promoting metabolic changes, dizziness, and nausea (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.), Kombucha tea is not toxic (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.). However, it should be used sparingly since it has been linked to liver toxicity, hyponatremia, and lactic acidosis (Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.). Accordingly, individuals with immune system disorders (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.), as well as kidney, liver, and lung diseases, must avoid drinking it (Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.). Its consumption is also contraindicated for pregnant women because it interferes with clotting processes and hence being harmful to fetal development (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Daily consumption of 118 mL Kombucha poses no risk to consumers (Anonym, 1995 Anonym . Unexplained severe illness possibly associated with consumption of Kombucha tea-Iowa, 1995. Morb Mortal Wkly Rep. 1995;44(48):892-3,899-900.).

Still, there is no consensus on a daily Kombucha intake. Currently, it is suggested to be between 100 and 300 mL (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.). Above 355 mL, it was reported to promote metabolic acidosis in 2 patients (Nummer, 2013Nummer BA. Kombucha brewing under the food and drug administration model Food Code: Risk analysis and processing guidance. J Environ Health. 2013;76(4):8-11.). A continuous 12-week intake by rats has shown to promote internal perforations of organs, kidney injuries, and necrosis in duodenum, pancreas, and intestine (Greenwalt et al., 2000Greenwalt CJ, Steinkraus KH, Ledford RA. Kombucha, the fermented tea: microbiology, composition, and claimed health effects. J Food Protect. 2000;63(7):976-81.; Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.). Hyperthermia, lactic acidosis, and kidney failure have also been reported in one HIV carrier 15 hours after drinking the tea. Another study showed that its consumption by 4 HIV patients promoted an allergic reaction, jaundice, nausea, vomiting, and neck and head pains (Jayabalan et al., 2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.). One individual was told to die of intestinal tract perforations and severe acidosis (Perry, 1995Perry N. Culture shock. Emerg Med Serv. 1995;24:35-6.). Liver toxicity has been observed after 2-year Kombucha consumption (Kovacevic et al., 2014Kovacevic Z, Davidovic G, Vuckovic-Filipovic J, Janicijevic-Petrovic MA, Janicijevic K, Popovic A. A toxic hepatitis caused the kombucha tea - case report. Open Access Maced J Med Sci. 2014;2(1):128-31.). Besides, hospitalization cases due to tea intake have been reported in patients with past health problems (Anonym, 1996 Anonym . Unexplained severe illness possibly associated with consumption of Kombucha tea-Iowa, 1995. From the Centers for Disease Control and Prevention. JAMA. 1996;275(2):96-8.).

Bactericidal and fungicidal effect

On the 14th day of Kombucha fermentation, it is rich in acetic acid, catechins, and isorhamnetin, with a bactericidal effect on enteric bacterial pathogens (e.g., Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Vibrio cholera) (Bhattacharya et al., 2016Bhattacharya D, Bhattacharya S, Patra MM, Chakravorty S, Sarkar S, Chakraborty W, et al. Antibacterial activity of polyphenolic fraction of kombucha against enteric bacterial pathogens. Curr Microbiol. 2016;73(6):885-96.). It also has an antibacterial activity against Agrobacterium tumefaciens, Escherichia coli, Helicobacter pylori, and Staphylococcus aureus (Steinkraus et al., 1996Steinkraus KH, Shapiro KB, Hotchkiss JH, Mortlock RP. Investigations into the antibiotic activity of tea fungus/ Kombucha beverage. Acta Biotechnol. 1996;16(2-3):199-205.). Kombucha tea with 0.7% acetic acid is reported to have in vitro antimicrobial activity against Agrobacterium tumefaciens, Bacillus cereus, Escherichia coli, and Staphylococcus aureus (Greenwalt et al., 1998Greenwalt CJ, Ledford RA, Steinkraus KH. Determination and characterization of the antimicrobial activity of the fermented tea Kombucha. LWT -Food Sci Technol . 1998;31(3):291-6.). Kombucha has antimicrobial properties that can remain neutralized up to pH 7 when heated at 80 oC for 30 minutes (Sreeramulu, Zhu, Knol, 2000Sreeramulu G, Zhu Y, Knol W. Kombucha fermentation and its antimicrobial activity. J Agr Food Chem. 2000;48(6):2589-94.).

Ethyl acetate in Kombucha tea has an in vitro antifungal effect on Malassezia species (Mahmoudi et al., 2016Mahmoudi E, Saeidi M, Marashi MA, Moafi A, Mahmoodi V, Zeinolabedini ZM. In vitro activity of kombucha tea ethyl acetate fraction against Malassezia species isolated from seborrhoeic dermatitis. Curr Med Mycol. 2016;2(4):30-6.).

Effect on some diseases

Several studies have been carried out on animal models (e.g., cats, chickens, cows, dogs, ducks, mice, pigs, rabbits, and rats) and human lymphocytes (Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.) to evaluate Kombucha effects on blood pressure and serum cholesterol levels, cancer scattering, as well as on the functioning of the liver and the gastric and immune systems (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.).

Flavonoids and other polyphenols produced during Kombucha fermentation (Figure 2) are suggested to confer beneficial effects in prevention and treatment of diseases (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.; Kapp, Sumner, 2019Kapp JM, Sumner W. Kombucha: a systematic review of the empirical evidence of human health benefit. Ann Epidemiol. 2019;30:66-70.), as they inhibit hydrolytic and oxidative activities of some enzymes, besides their anti-inflammatory effects (Pakravan et al., 2018Pakravan N, Mahmoudi E, Hashemi S-A, Kamali J, Hajiaghayi R, Rahimzadeh M, et al. Cosmeceutical effect of ethyl acetate fraction of kombucha tea by intradermal administration in the skin of aged mice. J Cosmet Dermatol. 2018;17(6):1216-24.).

FIGURE 2
Effect of kombucha consumption on the treatment of diseases.

Tea type and SCOBY microorganisms have a direct influence on levels of polyphenols (May et al., 2019 May A, Narayanan S, Alcock J, Varsani A, Maley C, Aktipis A. Kombucha: a novel model system for cooperation and conflict in a complex multi-species microbial ecosystem. PeerJ. 2019;7:e7565.), which have antioxidant actions. These concentrations progressively increase during Kombucha fermentation until reaching their highest contents on the 12th day (Bhattacharya, Ahmed, Chakraborty, 2011Bhattacharya S, Ahmed KKM, Chakraborty S. Free radicals cardiovascular diseases: An update. Free Radicals Antioxid. 2011;1(1):17-22.). However, Kombucha beneficial effects have already been attributed to bacteria (Acetobacter and Gluconobacter) and yeasts (Saccharomyces) that produce glucuronic acid (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Below are the findings of studies on Kombucha use for the treatment of diseases.

Liver disease

Non-alcoholic fatty liver disease results from an accumulation of lipids in the liver and can occur due to the consumption of high-fat or low choline and methionine diets by sedentary and obese individuals (Jung et al., 2019Jung Y, Kim I, Mannaa M, Kim J, Wang S, Park I, et al. Effect of Kombucha on gut-microbiota in mouse having non-alcoholic fatty liver disease. Food Sci Biotechnol . 2019;28(1):261-7.). Kombucha was reported to act on rat intestinal flora, decreasing bacterial population (Allobaculum and Turicibacter) involved in non-alcoholic liver sclerosis, and increasing Mucispirillum population. The latter has a positive effect on the secretion of leptin, which is a hormone that regulates hunger and stimulates lipolysis, thus improving oxidation of fat stored in the liver. Such microbiota change is suggested to improve non-alcoholic liver sclerosis (Jung et al., 2019Jung Y, Kim I, Mannaa M, Kim J, Wang S, Park I, et al. Effect of Kombucha on gut-microbiota in mouse having non-alcoholic fatty liver disease. Food Sci Biotechnol . 2019;28(1):261-7.). For 3 weeks and together with a healthy diet, Kombucha is said to increase lipolysis in obese mice and attenuate fat accumulation in the liver, thus preventing progression of non-alcoholic fatty liver disease (Hyun et al., 2016Hyun J, Lee Y, Wang S, Kim J, Kim J, Cha J, et al. Kombucha tea prevents obese mice from developing hepatic steatosis and liver damage. Food Sci Biotechnol. 2016;25(3):861-6.).

Kombucha proved to reverse liver problems caused by carbon tetrachloride poisoning (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). The drink has glucuronic acid, which acts in the hepatic detoxification of drugs and metabolism of bilirubin (Nguyen et al., 2015Nguyen NK, Nguyen PB, Nguyen HT, Le PH. Screening the optimal ratio of symbiosis between isolated yeast and acetic acid bacteria strain from traditional kombucha for high-level production of glucuronic acid. LWT-Food Sci Technol . 2015;64(2):1149-55.).

Cancer

In rats with breast cancer, ginger Kombucha (Zingiber officinale) promoted tumor homogeneity and reduced activity of enzymes (e.g., catalase, glutathione peroxidase, and superoxide dismutase) that control reactive oxygen and nitrogen species, besides reducing molecular marker of oxidative stress (malondialdehyde). Also, free radicals widely produced in anaerobic cancer metabolism decrease (Salafzoon, Hosseini, Halabian, 2017Salafzoon S, Hosseini HM, Halabian R. Evaluation of the antioxidant impact of ginger-based kombucha on the murine breast cancer model. J Complement Integr Med. 2017;15(1) doi: 10.1515/jcim-2017-0071.
https://doi.org/10.1515/jcim-2017-0071....
).

Kombucha tea reduces survival of prostate cancer cells and their metastasis by altering expression of angiogenic stimulators such as HIF-1α (hypoxia-inducible factor-1α), IL-8 (interleukin-8), VEGF (vascular endothelial growth factor), COX-2 (cyclooxygenase 2), MMP-2 (metalloproteinase 2), and MMP-9 (metalloproteinase 9). These findings suggest that a daily and limited consumption of Kombucha drink could prevent and treat neoplastic cell proliferation (Srihari et al., 2013Srihari T, Arunkumar R, Arunakaran J, Satyanarayana U. Downregulation of signalling molecules involved in angiogenesis of prostate cancer cell line (PC-3) by kombucha (lyophilized). Biomed Prev Nutr. 2013;3(1):53-8.).

Jayabalan et al. (2014 Jayabalan R, Malbaša RV, Lončar ES, Vitas JS, Sathishkumar M. A review on kombucha tea-microbiology, composition, fermentation, beneficial effects, toxicity, and tea fungus. Compr Rev Food Sci Food Saf. 2014;13(4):538-50.) noted that a Kombucha ethyl acetate fraction shows cytotoxic activities against human renal carcinoma cells (786-0) and human osteosarcoma (U2OS) by decreasing metastasis.

Green tea (Camellia sinensis) reduces carcinoma cell growth by decreasing enzymatic actions (e.g., acetylase, kinase, and methylase). The polyphenols in the drink act against cancer by decreasing free radicals (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.).

Pollen, which is rich in polyphenolic compounds and short-chain fatty acids, stimulates fermentation by Kombucha microorganisms and increases phytonutrient bioavailability in beverages, which promote a moderate antitumor effect on Caco-2 cells (Uțoiu et al., 2018Uţoiu E, Matei F, Toma A, Diguţă CF, Ştefan LM, Mănoiu S, et al. Bee collected pollen with enhanced health benefits, produced by fermentation with a kombucha consortium. Nutrients . 2018;10(10):1365.).

Diabetes mellitus and dyslipidemia

Kombucha increased the number of beta cells in the pancreas of rats and decreased fasting glucose and oxidative stress (Aloulou et al., 2012Aloulou A, Hamden K, Elloumi D, Ali MB, Hargafi K, Jaouadi B, et al. Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats. BMC Complementary Altern Med. 2012;12:63.; Zubaidah et al., 2019Zubaidah E, Afgani CA, Kalsum U, Srianta I, Blanc PJ. Comparison of in vivo antidiabetes activity of snake fruit Kombucha, black tea Kombucha and metformin. Biocatal Agric Biotechnol. 2019;17:465-9.).

Aloulou et al. (2012Aloulou A, Hamden K, Elloumi D, Ali MB, Hargafi K, Jaouadi B, et al. Hypoglycemic and antilipidemic properties of kombucha tea in alloxan-induced diabetic rats. BMC Complementary Altern Med. 2012;12:63.) observed that a daily administration of 5 mL/kg Kombucha in diabetic rats for 30 days inhibits α-amylase and lipase and results in lower postprandial glycemia. It also improves renal function and decreases levels of creatinine, urea, and activity of serum enzymes (e.g., alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase).

Likewise, Bellassoued et al. (2015Bellassoued K, Ghrab F, Makni-Ayadi F, Pelt JV, Elfeki A, Ammar E. Protective effect of kombucha on rats fed a hypercholesterolemic diet is mediated by its antioxidant activity. Pharm Biol. 2015;53(11):1699-709.) administered daily 5 mL Kombucha/kg rat body weight for 16 weeks and noted improvements in renal function and hypercholesterolemia by decreasing levels of triglycerides, total cholesterol, VLDL-C (very-low-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), and lipid peroxidation, while increasing HDL-C (high-density lipoprotein cholesterol) and levels of antioxidant molecules.

El-Saied, Basta, Gobran (2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.) highlighted that when Gluconacetobacter xylinus is added to coconut milk, its biocellulose decreased plasma cholesterol.

VARIETY OF KOMBUCHA USE

Beverage

Kombucha tea can be used in the cosmetics industry and food nutritional enrichment (Xia et al., 2019Xia X, Dai Y, Wu H, Liu X, Wang Y, Yin L, et al. Kombucha fermentation enhances the health-promoting properties of soymilk beverage. J Funct Foods . 2019;62:103549.). Pakravan et al. (2018Pakravan N, Mahmoudi E, Hashemi S-A, Kamali J, Hajiaghayi R, Rahimzadeh M, et al. Cosmeceutical effect of ethyl acetate fraction of kombucha tea by intradermal administration in the skin of aged mice. J Cosmet Dermatol. 2018;17(6):1216-24.) showed that intradermal injection of Kombucha ethyl acetate fraction, with high flavonoid contents, promoted neither skin sensitivity nor irritation. It actually increased collagen production in elderly mice with dyschromia and wrinkles, which result from reductions in collagen fibers and dysfunctions in melanocytic cells and keratinocytes.

After Kombucha injection, skin appearance improved, which has been attributed to flavonoids (Moulishankar, Lakshmanan, 2020Moulishankar A, Lakshmanan K. Data on molecular docking of naturally occurring flavonoids with biologically important targets. Data Brief. 2020;29:105243.), anti-inflammatory compounds (Fernández-Rojas, Gutiérrez-Venegas, 2018Fernández-Rojas B, Gutiérrez-Venegas G. Flavonoids exert multiple periodontic benefits including anti-inflammatory, periodontal ligament-supporting, and alveolar bone-preserving effects. Life Sci. 2018;209:435-54.), amino acids, antioxidants, minerals, polyphenols, vitamins, and enzymes. Such compounds reduce skin inflammation, free radicals, and UV ray penetration, allowing cellular DNA protection (Bhattacharya, Ahmed, Chakraborty, 2011Bhattacharya S, Ahmed KKM, Chakraborty S. Free radicals cardiovascular diseases: An update. Free Radicals Antioxid. 2011;1(1):17-22.; Pakravan et al., 2018Pakravan N, Mahmoudi E, Hashemi S-A, Kamali J, Hajiaghayi R, Rahimzadeh M, et al. Cosmeceutical effect of ethyl acetate fraction of kombucha tea by intradermal administration in the skin of aged mice. J Cosmet Dermatol. 2018;17(6):1216-24.). Thus, Kombucha use has been suggested for the preparation of cosmetics, so that it could promote skin improvement or regeneration in the elderly (Pakravan et al., 2018Pakravan N, Mahmoudi E, Hashemi S-A, Kamali J, Hajiaghayi R, Rahimzadeh M, et al. Cosmeceutical effect of ethyl acetate fraction of kombucha tea by intradermal administration in the skin of aged mice. J Cosmet Dermatol. 2018;17(6):1216-24.).

Kombucha SCOBY is used in the industry for the production of fermented foods (Soares, Lima, Schmidt, 2021Soares MG, Lima M, Schmidt VCR. Technological aspects of Kombucha, its applications and the symbiotic culture (SCOBY), and extraction of compounds of interest: A literature review. Trends Food Sci Technol . 2021;110:539-50.). When fermented with Kombucha, soy milk has its total contents of phenolic compounds and vitamins increased, which improves its nutritional quality (Xia et al., 2019Xia X, Dai Y, Wu H, Liu X, Wang Y, Yin L, et al. Kombucha fermentation enhances the health-promoting properties of soymilk beverage. J Funct Foods . 2019;62:103549.).

Biocellulose

Microbial-produced biocellulose is a substitute for plant-synthesized cellulose and can be used to reduce environmental impacts.

In Kombucha production, biocellulose is disposed of during filtration (Soares, Lima, Schmidt, 2021Soares MG, Lima M, Schmidt VCR. Technological aspects of Kombucha, its applications and the symbiotic culture (SCOBY), and extraction of compounds of interest: A literature review. Trends Food Sci Technol . 2021;110:539-50.). But it has economic value and can be used as a raw material in the textile industry. This is because after its dehydration it looks like leather. For this reason, it has been useful in the manufacturing of clothing and bags (Tünay et al., 1995Tünay O, Kabdaşli I, Orhon D, Ates E. Characterization and pollution profile of leather tanning industry in Turkey. Water Sci Technol. 1995;32(12):1-9.; Ghalachyan, 2017; Domskiene, Sederavičiūtė, Simonaityte, 2019Domskiene J, Sederavičiūtė F, Simonaityte J. Kombucha bacterial cellulose for sustainable fashion. Int J Cloth Sci Tech. 2019;31(5). doi: 10.1108/IJCST-02-2019-0010.
https://doi.org/10.1108/IJCST-02-2019-00...
; Kamiński et al., 2020Kamiński K, Jarosz M, Grudzień J, Pawlik J, Zastawnik F, Pandyra P, et al. Hydrogel bacterial cellulose: a path to improved materials for new eco-friendly textiles. Cellulose. 2020;27:5353-65.), in addition to cigarette papers (Shaun, Cutter, 2019Shaun M, Cutter G. Cigarette rolling papers formed from kombucha biofilms [Internet]. 2019. [citad 2022 Set 22]. Available from: Available from: http://www.freepatentsonline.com/ y2019/0174815.html .
http://www.freepatentsonline.com/ y2019/...
).

Biocellulose can be produced from microorganisms of the genera Achromobacter, Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Dickeya, Gluconacetobacter, Pseudomonas, Rhizobium, Rhodobacter, and Sarcina. The Gluconacetobacter is the main producer when using carbon and nitrogen sources (Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.).

Bacterial cellulose can be produced in juices (e.g., muskmelon, orange, pear, pineapple, pomegranate, sugarcane juice, tomato, and watermelon), molasses, starch hydrolysate, coconut milk, coconut water (Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.), and sisal juice (Lima et al., 2017Lima HLS, Nascimento ES, Andrade FK, Brígida AIS, Borges MF, Cassales AR, et al. Bacterial cellulose production by Komagataeibacter hansenii ATCC 23769 using sisal juice - an agroindustry waste. Braz J Chem Eng. 2017;34(3):671-80.).

Due to its characteristics such as biodegradability, crystallization index, fiber composition, hydrophilicity, mechanical properties, purity, transparency, and water-holding capacity, microbial biocellulose is a biopolymer with applications in the following areas: food (e.g., dietary fiber, enzyme immobilization, and functional packaging), biomedical (e.g., artificial bone, artificial skin, cartilage, cell therapy, dental implant components, medical pads, regenerative tissues, scaffold tissues, vascular grafts, and wound care), pharmaceutical (e.g., delivery of drugs, film coating, hormones, and proteins), engineering (e.g., flat panel display, nanocomposites, and soil conditioning), environmental (e.g., biosensors, degradation pollutants, dye decolorization, and heavy metal removal) (Reiniati, Hrymak, Margaritis, 2017Reiniati I, Hrymak AN, Margaritis A. Recent developments in the production and applications of bacterial cellulose fibers and nanocrystals. Crit Rev Biotechnol. 2017;37(4):510-24.; Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.; Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.; Soares, Lima, Schmidt, 2021Soares MG, Lima M, Schmidt VCR. Technological aspects of Kombucha, its applications and the symbiotic culture (SCOBY), and extraction of compounds of interest: A literature review. Trends Food Sci Technol . 2021;110:539-50.).

Kombucha biocellulose can be used as a dietary matrix and source of fiber (Keshk, 2014Keshk SMAS. Bacterial cellulose production and its industrial applications. J Bioprocess Biotech. 2014;4(2):1-10.) to produce dietary foods, as its fibers do not undergo enzymatic digestion in the human digestive tract (Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.). Some bacteria and yeasts adhere to gelatinous layers, which can be dehydrated and improve the quality of ingested diet (Leal et al., 2018 Leal JM, Suárez LV, Jayabalan R, Oros JH, Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA-J Food. 2018;16(1):390-9.). Nata-de-coco is one of the Filipino favorite desserts and has gained prominence in other parts of the world (El-Saied, Basta, Gobran, 2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.; Keshk, 2014Keshk SMAS. Bacterial cellulose production and its industrial applications. J Bioprocess Biotech. 2014;4(2):1-10.). This sweet can be produced in several manners such as custard cream (with pineapple juice) (Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.).

Other cellulose biomembranes have been widely used. In medicine, gelatinous biocellulose membranes have been used since the 1990s as an artificial substitute for burns, grafts, skin, ulcers, and as an adjuvant in dermal abrasions (Fontana et al., 1991Fontana JD, Franco VC, Souza SJ, Lyra IN, Souza AM. Nature of plant stimulators in the production of Acetobacter xylinum (‘‘tea fungus’’) biofilm used in skin therapy. Appl Biochem Biotechnol. 1991;28:341-51.). Acetobacter xylinum-derived biocellulose can be used as artificial skin in areas of low mobility due to its permeability for liquids and gases and low irritability. The bacterial cellulose product Biofill® is used as a skin substitute for burns (2nd and 3rd degree) and ulcers, with the following advantages: close wound bed adhesion, diminished post-surgery discomfort, faster healing, immediate pain relief, improved exudates retention, reduced infection rate, spontaneous detachment following reepithelization, wound inspection easiness (transparency), as well as reduced treatment time and costs (Keshk, 2014Keshk SMAS. Bacterial cellulose production and its industrial applications. J Bioprocess Biotech. 2014;4(2):1-10.). Moreover, other products such as Gengiflex® and Cellumed are used in dentistry and veterinary medicine. The latter is applied in the treatment of dogs and horses, replacing the duramater in the brain (El-Saied, Basta, Gobran, 2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.).

In Brazil, a purified gelatinous membrane from bacterial cellulose has been commercialized as artificial skin for being superior to conventional gauze to temporarily cover the skin (Fontana et al., 1991Fontana JD, Franco VC, Souza SJ, Lyra IN, Souza AM. Nature of plant stimulators in the production of Acetobacter xylinum (‘‘tea fungus’’) biofilm used in skin therapy. Appl Biochem Biotechnol. 1991;28:341-51.). Moreover, biocellulose has also been used as an artificial blood vessel (1 mm diameter, 5 mm length, and 0.7 mm wall thickness). It has lower risks than those synthetic ones used in bypass operations (Keshk, 2014Keshk SMAS. Bacterial cellulose production and its industrial applications. J Bioprocess Biotech. 2014;4(2):1-10.). Human plasma proteins (e.g., albumin, c-globulin, and fibrinogen) are reported to adhere to biocellulose blood vessels with a tripeptide (Arg-Gly-Asp) in large quantities, without changing their structure. This suggests that biocellulose compatibility with blood could bring benefits to human health (Andrade et al., 2011Andrade FK, Silva JP, Carvalho M, Castanheira EMS, Soares R, Gama M. Studies on the hemocompatibility of bacterial cellulose. J Biomed Mater Res A. 2011;98(4):554-66.).

Biocellulose can be used to manufacture paper (El-Saied, Basta, Gobran, 2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.) since its cellulose microfibers contribute to durability (El-Saied, Basta, Gobran, 2004; Keshk, 2014Keshk SMAS. Bacterial cellulose production and its industrial applications. J Bioprocess Biotech. 2014;4(2):1-10.). Padrão et al. (2016Padrão J, Gonçalves S, Silva JP, Sencadas V, Lanceros-Méndez S, Pinheiro AC, et al. Bacterial cellulose-lactoferrin as an antimicrobial edible packaging. Food Hydrocoll. 2016;58:126-40.) modified a bacterial cellulose film for bovine lactoferrin adsorption on fresh sausage, and it showed 94% inhibition of Escherichia coli and Staphylococcus aureus. Moreover, biocellulose has also been used as a fat substitute (Azeredo et al., 2019Azeredo HMC, Barud H, Farinas CS, Vasconcellos VM, Claro AM. Bacterial cellulose as a raw material for food and food packaging applications. Front Sustain Food Syst. 2019;3:1-14.) for the production of meatballs (Lin, Lin, 2004Lin KW, Lin HY. Quality characteristics of Chinese-style meatball containing bacterial cellulose (Nata). J Food Sci. 2004; 69(3):SNQ107-SNQ11.) and ice cream (Guo et al., 2018Guo Y, Zhang X, Hao W, Xie Y, Chen L, Li Z, et al. Nano-bacterial cellulose/soy protein isolate complex gel as fat substitutes in ice cream model. Carbohydr Polym. 2018;198:620-30.).

Bacterial cellulose has shown satisfactory results in biometric applications due to its binding to the metals (Au3+, Cu1+, and Pt1+) (Cottet et al., 2020Cottet C, Ramirez-Tapias YA, Delgado JF, la Osa O, Salvay AG, Peltzer MA. Biobased materials from microbial biomass and its derivatives. Materials. 2020;13(6):1263.), as well as in environmental applications due to its capacity to bind heavy metals (Cd2+, Ni2+, and Pb2+) (Cerrutti et al., 2016Cerrutti P, Roldán P, García RM, Galvagno MA, Vázquez A, Foresti ML. Production of bacterial nanocellulose from wine industry residues: Importance of fermentation time on pellicle characteristics. J Appl Polym Sci. 2016;133(14):1-9.). As biocellulose microorganisms remove heavy metals (As3+, Cd2+, Cr6+, Hg2+, and Pb2+), they can be used in environmental decontamination (Najafpour et al., 2020Najafpour A, Khorrami AR, Azar PA, Tehrani MS. Study of heavy metals biosorption by tea fungus in Kombucha drink using Central Composite Design. J Food Compos Anal. 2020;86:103359.). In the field of electronics, biocellulose was used to develop the first headphone (El-Saied, Basta, Gobran, 2004El-Saied H, Basta AH, Gobran RH. Research progress in friendly environmental technology for the production of cellulose products (bacterial cellulose and its application). Polymer-Plast Technol Eng. 2004;43(3):797-820.).

CONCLUSIONS

Kombucha fermented drink is a symbiotic food product that is easy to prepare and can be used as a functional beverage. When used sparingly, it improves human health in prevention and treatment of pathologies, as it contains several chemical compounds and species of bacteria and yeasts. Its biocellulose layer can be used as raw material for medicine and in the textile, food, and environmental industries, resulting in a reduction in the emission of pollutants from industrial production. Both can be used as functional foods and/or sources of bioactive compounds for food and industrial applications.

Some doubts remain about dosage, frequency, and duration of consumption for populations in different regions of the planet. Thus, studies with groups of animals and human beings are needed, as symbiotic yeasts are known and used worldwide.

ACKNOWLEDGMENTS

Zenaide Moschim Gianini (http://lattes.cnpq.br/2189344499213658) for the translation of the article.

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Publication Dates

  • Publication in this collection
    16 Jan 2023
  • Date of issue
    2022

History

  • Received
    12 Aug 2020
  • Accepted
    05 Apr 2021
Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br