Uso de probióticos e similares em pacientes pediátricos com Diabetes <i>Mellitus</i> tipo 1: uma revisão sistemática

Neiva, Luisa Pinheiro; Lopez, Luiza Correia; Pasiani, Rafaela Orsi; Serra, Mayco José Reinaldi; Rullo, Vera Esteves Vagnozzi

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Brasil

Revista Paulista de Pediatria

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Brasil

Español English

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Sumário

Review Article • Rev. paul. pediatr. 42 • 2024 • https://doi.org/10.1590/1984-0462/2024/42/2023097 copiar

Uso de probióticos e similares em pacientes pediátricos com Diabetes Mellitus tipo 1: uma revisão sistemática

Autoria SCIMAGO INSTITUTIONS RANKINGS

RESUMO

Objetivo:

Realizar uma revisão sistemática de ensaios clínicos randomizados controlados avaliando o efeito da suplementação de probióticos, prebióticos ou simbióticos no controle glicêmico e inflamatório em crianças com diabetes mellitus tipo 1 (DM1).

Fontes de dados:

As bases Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e Scientific Electronic Library Online (SciELO) foram pesquisadas. Foram incluídos ensaios clínicos randomizados de pacientes pediátricos com DM1 em uso de probióticos, prebióticos ou simbióticos, independentemente de ano ou idioma de publicação. Foram excluídos os trabalhos que não avaliaram hemoglobina glicada (HbA1c). Os resultados metabólicos (HbA1c, dose de insulina total e peptídeo C) e o controle inflamatório [interleucina-10 — IL-10), fator de necrose tumoral-alfa (TNF-α) e interferon-gama (IFN-γ)] durante a suplementação de probióticos ou similares, relacionados à modificação da microbiota intestinal, foram analisados. ID PROSPERO: CRD42022384485.

Síntese dos dados:

Cinco estudos foram selecionados para revisão sistemática. Com relação aos marcadores metabólicos, apenas um dos artigos que analisaram a HbA1c apresentou diminuição significativa (p=0,03) no grupo intervenção. Um estudo identificou redução da dose total de insulina e aumento dos níveis de peptídeo C. Quanto à avaliação dos parâmetros inflamatórios (IL-10, TNF-α, INF-γ), não houve modificações de relevância estatística.

Conclusões:

Os dados atuais da literatura não foram conclusivos em identificar melhora no controle glicêmico e não observaram mudanças nos parâmetros inflamatórios com o uso de probióticos, prebióticos ou simbióticos em pacientes pediátricos com DM1.

Palavras-chave:
Hemoglobina A glicada; Diabetes mellitus tipo 1; Probióticos; Controle glicêmico; Citocinas

Assessed domain	I	II.1	II.2	III	IV	V	Final classification
Wang et al.¹⁸18 Wang CH, Yen HR, Lu WL, Ho HH, Lin WY, Kuo YW, et al. Adjuvant probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in patients with Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne). 2022;13:754401. https://doi.org/10.3389/fendo.2022.754401 https://doi.org/10.3389/fendo.2022.75440...
Kumar et al.¹⁹19 Kumar S, Kumar R, Rohilla L, Jacob N, Yadav J, Sachdeva N. A high potency multi-strain probiotic glycemic control in children with new-onset type 1 diabetes mellitus: a randomized, double-blind, and placebo controlled pilot study. Pediatr Diabetes. 2021;22:1014-22. https://doi.org/10.1111/pedi.13244 https://doi.org/10.1111/pedi.13244...
Groele et al.²⁰20 Groele L, Szajewska H, Szalecki M, Świderska J, Wysocka-Mincewicz M, Ochocińska A, et al. Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care. 2021;9:e001523. https://doi.org/10.1136/bmjdrc-2020-001523 https://doi.org/10.1136/bmjdrc-2020-0015...
Javid et al.²¹21 Javid AZ, Aminzadeh M, Haghighi-Zadeh MH, Jamalvandi M. The effects of symbiotic supplementation on glycemic status, lipid profile, and biomarkers of oxidative stress in type 1 diabetic patients: a placebo-controlled, double-blind, randomized clinical trial. Diabetes Metab Syndr Obes. 2020;13:607-17. https://doi.org/10.2147/DMSO.S238867 https://doi.org/10.2147/DMSO.S238867...
Ho et al.²²22 Ho J, Nicolucci AC, Virtanen H, Schick A, Meddings J, Reimer RA, et al. Effect of prebiotic on microbiota, intestinal permeability, and glycemic control in children with type 1 diabetes. J Clin Endocrinol Metab. 2019;104:4427-40. https://doi.org/10.1210/jc.2019-00481 https://doi.org/10.1210/jc.2019-00481...

Author and country	Age studied	T1DM diagnosis time	Probiotics or similar and doses	No. of the total sample (probiotic x placebo)	Follow-up time
Wang et al.¹⁸18 Wang CH, Yen HR, Lu WL, Ho HH, Lin WY, Kuo YW, et al. Adjuvant probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in patients with Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne). 2022;13:754401. https://doi.org/10.3389/fendo.2022.754401 https://doi.org/10.3389/fendo.2022.75440... ; Taiwan	6–18 years	Long-term diabetic patients who have already experienced the honeymoon period	Probiotics^* * L. salivarius subesp. salicinius AP-32, L. johnsonii MH-68 and B. animalis subesp. lactis CP-9 10¹⁰ CFU/day or placebo orally for 6 months	59 (27×32)	9 months
Kumar et al.¹⁹19 Kumar S, Kumar R, Rohilla L, Jacob N, Yadav J, Sachdeva N. A high potency multi-strain probiotic glycemic control in children with new-onset type 1 diabetes mellitus: a randomized, double-blind, and placebo controlled pilot study. Pediatr Diabetes. 2021;22:1014-22. https://doi.org/10.1111/pedi.13244 https://doi.org/10.1111/pedi.13244... ; India	2–12 years	T1DM of recent onset (within 6 months of enrollment)	Probiotics^† † Live, freeze-dried, lactic and bifidobacteria named L paracasei DSM 24733, L plantarum DSM 24730, L acidophilus DSM 24735, L delbrueckii subsp. bulgaricus DSM 24734, B longum DSM 24736, B children’s DSM 24737, B brief DSM 24732 and Streptococcus thermophilus DSM 24731 112.5 billion CFU/day or microcrystalline cellulose for 3 months	96 (47×49)	3 months
Groele et al.²⁰20 Groele L, Szajewska H, Szalecki M, Świderska J, Wysocka-Mincewicz M, Ochocińska A, et al. Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care. 2021;9:e001523. https://doi.org/10.1136/bmjdrc-2020-001523 https://doi.org/10.1136/bmjdrc-2020-0015... ; Varsovia, Poland	8–17 years	Recent diagnosis (within 60 days)	Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 10⁹ CFU colony or placebo (maltodextrin) orally capsule once a day for 6 months	96 (48×48)	12 months
Javid et al.²¹21 Javid AZ, Aminzadeh M, Haghighi-Zadeh MH, Jamalvandi M. The effects of symbiotic supplementation on glycemic status, lipid profile, and biomarkers of oxidative stress in type 1 diabetic patients: a placebo-controlled, double-blind, randomized clinical trial. Diabetes Metab Syndr Obes. 2020;13:607-17. https://doi.org/10.2147/DMSO.S238867 https://doi.org/10.2147/DMSO.S238867... ; Shiraz, Iran	4–18 years	At least 1 year with diagnosis of DM1	2 g symbiotic powder^‡ ‡ Symbiotic powder: Lactobacillus sporogenes GBI-30 (probiotic), maltodextrin and fructooligosaccharide (prebiotic). (109 CFU) for 8 weeks	50 (25×25)	8 weeks
Ho et al.²²22 Ho J, Nicolucci AC, Virtanen H, Schick A, Meddings J, Reimer RA, et al. Effect of prebiotic on microbiota, intestinal permeability, and glycemic control in children with type 1 diabetes. J Clin Endocrinol Metab. 2019;104:4427-40. https://doi.org/10.1210/jc.2019-00481 https://doi.org/10.1210/jc.2019-00481... ; Canada	8–17 years	At least 1 year with diagnosis of DM1	8g oligofructose-enriched inulin orally once a day or placebo 3.3g maltodextrin orally once a day for 12 weeks	43 (20×23)	6 weeks

			HbA1c (%)		Total insulin dose (μg/mL)		C-peptide (ng/mL)
			M±SD	p-value	M±SD	p-value	M±SD	p-value
Wang et al.¹⁸18 Wang CH, Yen HR, Lu WL, Ho HH, Lin WY, Kuo YW, et al. Adjuvant probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in patients with Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne). 2022;13:754401. https://doi.org/10.3389/fendo.2022.754401 https://doi.org/10.3389/fendo.2022.75440... ; Taiwan	Basal	I	9.3±0.80	0.883
	Basal	C	9.5±1.90	0.883
	After 6 m	I	8.5±0.90	NI
	After 6 m	C	9.5±2.10	NI
Kumar et al.¹⁹19 Kumar S, Kumar R, Rohilla L, Jacob N, Yadav J, Sachdeva N. A high potency multi-strain probiotic glycemic control in children with new-onset type 1 diabetes mellitus: a randomized, double-blind, and placebo controlled pilot study. Pediatr Diabetes. 2021;22:1014-22. https://doi.org/10.1111/pedi.13244 https://doi.org/10.1111/pedi.13244... ; India	Basal	I	11.7±1.63	0.512	1.0±0.45	0.183	0.3±0.35	0.866
	Basal	C	11.5±2.26		0.9±0.40		0.3±0.45
	After 3 m	I	6.8±1.46		0.6±0.31		0.5±0.40
	After 3 m	C	7.4±1.46		0.7±0.40		0.5±0.35
Groele et al.²⁰20 Groele L, Szajewska H, Szalecki M, Świderska J, Wysocka-Mincewicz M, Ochocińska A, et al. Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care. 2021;9:e001523. https://doi.org/10.1136/bmjdrc-2020-001523 https://doi.org/10.1136/bmjdrc-2020-0015... ; Poland	Basal	I	7.7±0.41	NI			1.0±0.27	NI
	Basal	C	8.3±0.72	NI			1.0±0.34	NI
	After 6m	I	6.1±0.35	0.058			0.9±0.26	0.832
	After 6m	C	6.5±0.39	0.058			0.9±0.27	0.832
Javid et al.²¹21 Javid AZ, Aminzadeh M, Haghighi-Zadeh MH, Jamalvandi M. The effects of symbiotic supplementation on glycemic status, lipid profile, and biomarkers of oxidative stress in type 1 diabetic patients: a placebo-controlled, double-blind, randomized clinical trial. Diabetes Metab Syndr Obes. 2020;13:607-17. https://doi.org/10.2147/DMSO.S238867 https://doi.org/10.2147/DMSO.S238867... ; Iran	Basal	I	8.9±1.95	0.270^* * Used the independent t-test between the two groups before and after the intervention	6.4±6.32	0.810^* * Used the independent t-test between the two groups before and after the intervention
	Basal	C	9.6±2.23		6.0±5.02
	After 8 w	I	8.6±1.85	0.960^* * Used the independent t-test between the two groups before and after the intervention	10.9±8.20	0.150^* * Used the independent t-test between the two groups before and after the intervention
	After 8 w	C	9.1±2.59		7.6±7.12
		≠ I	-0.3±0.52	0.030^† † Analysis of covariance (ANCOVA) was performed between the two post-intervention groups after adjustment for confounding factors.	4.5±4.53	0.060^† † Analysis of covariance (ANCOVA) was performed between the two post-intervention groups after adjustment for confounding factors.
		≠ C	-0.5±1.36		1.6±5.46
Ho et al.²²22 Ho J, Nicolucci AC, Virtanen H, Schick A, Meddings J, Reimer RA, et al. Effect of prebiotic on microbiota, intestinal permeability, and glycemic control in children with type 1 diabetes. J Clin Endocrinol Metab. 2019;104:4427-40. https://doi.org/10.1210/jc.2019-00481 https://doi.org/10.1210/jc.2019-00481... ; Canada	Basal	I	8.0±0.82	0.854	0.9±0.25	0.928	0.3±0.75	0.928
	Basal	C	8.1±0.91	0.854	0.9±0.29	0.928	0.2±0.30	0.928
	After 3 m	I	7.9±0.50	0.592	NI	NI	0.3±0.93	0.029
	After 3 m	C	8.1±0.91	0.592	NI	NI	0.1±0.15	0.029

			IL-10		TNF-α		IFN-γ
			M±SD	p-value	M±SD	p-value	M±SD	p-value
Wang et al.¹⁸18 Wang CH, Yen HR, Lu WL, Ho HH, Lin WY, Kuo YW, et al. Adjuvant probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in patients with Type 1 Diabetes Mellitus. Front Endocrinol (Lausanne). 2022;13:754401. https://doi.org/10.3389/fendo.2022.754401 https://doi.org/10.3389/fendo.2022.75440... ; Taiwan	Basal	I			52.5±59.70	0.810
	Basal	C			54.0±56.80	0.810
	After 6 m	I			39.2±47.50	NI
	After 6 m	C			49.3±57.20	NI
Groele et al.²⁰20 Groele L, Szajewska H, Szalecki M, Świderska J, Wysocka-Mincewicz M, Ochocińska A, et al. Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomized controlled trial. BMJ Open Diabetes Res Care. 2021;9:e001523. https://doi.org/10.1136/bmjdrc-2020-001523 https://doi.org/10.1136/bmjdrc-2020-0015... ; Poland	Basal	I	282.1±105.92	NI	4.6±5.29	NI
	Basal	C	186.6±85.92	NI	3.7±4.28	NI
	After 6 m	I	202.9±80.91	0.470	1.4±1.68	0.594
	After 6 m	C	161.9±75.65	0.470	4.7±5.46	NI
Ho et al.²²22 Ho J, Nicolucci AC, Virtanen H, Schick A, Meddings J, Reimer RA, et al. Effect of prebiotic on microbiota, intestinal permeability, and glycemic control in children with type 1 diabetes. J Clin Endocrinol Metab. 2019;104:4427-40. https://doi.org/10.1210/jc.2019-00481 https://doi.org/10.1210/jc.2019-00481... ; Canada	Basal	I	15.1±36.17	0.816	16.1±52.33	0.292	0.44±1.79	0.285
	Basal	C	13.0±17.91	0.816	3.9±1.75	0.292	0.02±0.04	0.285
	After 3 m	I	18.0±10.88	0.093	17.7±3.95	0.058	0.44±0.01	0.523
	After 3 m	C	7.0±18.16	0.093	3.6±1.52	0.058	0.01±0.04	0.523

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[1] Corresponding author. E-mail: luisapneiva@gmail.com (L. P. Neiva)