Holistic perspective of the role of gut microbes in diabetes mellitus and its management

Table 2 Selected animal studies showing the effect of various interventions on the gut microbiome and the role of gut microbiota in diabetes mellitus management

Intervention	Organism	Health benefit	Change in microbiome	Ref.
Intermittent fasting	Mice	Protection from diabetic retinopathy by increasing Tauroursodeoxycholate (a neuroprotective bile acid) producing microbes	Increased Firmicutes and decreased Bacteroidetes and Verrucomicrobia in diabetic mice undergoing intermittent fasting	Beli et al[73], 2018
Antibiotic treatment (ampicillin, metronidazole, neomycin, vancomycin, or their cocktail)	Mice	Reduction in fasting glucose. Change in glucose tolerance (seen with ampicillin, vancomycin, or cocktail)	Alterations in the α- and β- diversity. An association with Akkermansia mucinipjila with decrease fasting glucose. The effect is mediated through systemic changes in glucose metabolism	Rodrigues et al[94], 2017
Prebiotic: Acorn and sago	Mice	Mice fed acorn and sago derived prebiotics had an amelioration of the glucose intolerance and insulin resistance induced by a high-fat diet feeding. Intake of both novel prebiotics as well as inulin increases SCFAs levels in the mouse gut		Ahmadi et al[103], 2019
Combination of a functional fibre [PolyGlycopleX (PGX) with metformin (MET) or sitagliptin and metformin (S/MET)]	Mice	PGX + MET and PGX + S/MET showed reduced glycemia compared to controls and single treatment (P = 0.001). HbA1c was lower in PGX + S/MET compared to all other treatments (P = 0.001)		Reimer et al[93], 2014
Artificial sweetener (Neotame)	Mice	Decreased butyrate synthetic genes in Neotame group. Higher concentrations of cholesterol (P < 0.05) and fatty acids (P < 0.05) in Neotame treated mice feces	Reduction in α-diversity and altered β-diversity. Reduced Firmicutes (P < 0.01) and increased Bacteroides (P < 0.01)	Chi et al[85], 2018
Combination of metformin and a prebiotic [konjac mannan-oligosaccharides (MOS)]	Mice	Combination of metformin and MOS help ameliorate insulin resistance and improved glycemic control (P < 0.05) and repair islet and hepatic histology	Metformin and MOS change the microbiome (P < 0.0001) with: Decreased: Rikenellaceae and Clostridiales; Increased: Akkermansia muciniphila and Bifidobacterium pseudolongum	Zheng et al[96], 2018