Abstract

Background: Increasing loss of gut microbial diversity has been implicated in diabetes and prediabetes. Recent studies assessed the changes on microbiome composition due to interventions for diabetes treatment. Aim: This systematic review aimed to assess if dietary, surgical and pharmacological interventions can change gut microbiota in subjects with diabetes. Method: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement was followed for conducting and reporting this systematic review. A vote-counting method to assess the effect of interventions on relevant outcomes was applied. Inclusion criteria were: adults with type 1 or 2 diabetes diagnosis and focus on gut microbiota, which involved any intervention or combination of glycemic control interventions. The terms “diabetes mellitus” and “microbiota” were used in the selected databases in the article search. The studies were grouped by intervention type (dietary, surgical and pharmacological) and then classified based on their impact in the α-diversity and in individual bacterial abundances following the intervention. Results: The electronic search returned 5807 potentially relevant studies; after removing duplicates, 5218 studies were retained for review of titles and abstracts. The 130 full-text articles retained were reassessed, 37 of which were included. Dietary interventions that increased Lactobacillus genus include high consumption of lactic acid bacteria and oligosaccharides; an increase of Faecalibacterium was found in four studies. Concerning bariatric surgery, nine small studies with controversial results were examined. Among microbial species affected by the procedure, Veillonella was increased in seven studies, whereas the increase of genus Akkermansia was found only in one study. Nevertheless, the species Akkermansia muciniphila was increased in all types of interventions. Considering the pharmacological interventions, microbial α-diversity was reported in seven studies using different indices and methods, and studies indicated a significant difference in this index after the intervention with acarbose, metformin and metformin plus traditional Chinese medicine. The study with metformin reported an increase of Mobilitalea, Lactobacillus, Akkermansia and a decrease of Oscilibacter, Alloprevotella and Bifidobacterium. Discussion: Clinical heterogeneity precluded performing a meta-analysis. Analyzing the effects of interventions on gut microbial composition remains a challenge due to a multitude of factors. Overall, all three interventions increased more gram-positive bacteria from the Phylum Firmicutes than gram-negative bacteria from the Phylum Bacteroidetes. This balance may be suitable in patients with diabetes, once lipopolysaccharides produced by gram-negative bacterial cell may stimulate systemic inflammation, increasing insulin resistance. These results suggest that the interventions addressed to a reduction of species related to uncontrolled diabetes and to an increase of species related to a healthy gut.

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