Table 2.
Summary of the most significant gut microbial and host co-metabolites identified in the selected studies.
| Class | Metabolite | Disease | Change1 | Anti-T2D drugs effect | Sample | Interpretation | Reference | Related bacteria (phyla) |
|---|---|---|---|---|---|---|---|---|
| Bile acids (primary) | γ-muricholate (hyocholate) cholate glycochenodeoxycholate | Obesity + T2D | ↓ | Blood fluids | Bile acids are proposed as new metabolic integrators of whole body energy homeostasis that influence glucose and lipid metabolism. Subjects with diabetes exhibit alterations in the composition of the bile acid pool and their related biosynthetic pathway. A higher rate of conversion of primary to secondary bile acids by the gut microbiota has been implicated in the observed variation. | Suhre et al., 2010 | Firmicutes3 | |
| Obesity + T2D | ↓ | Blood fluids | Suhre et al., 2010 | |||||
| Obesity + pre-T2D | aaa | Blood fluids | Zhao et al., 2010 | |||||
| Bile acids (secondary) | Deoxycholate | Obesity + T2D | aaa | Blood fluids | Suhre et al., 2010 | |||
| Vitamin metabolites | Choline | (pre-)T2D | ↓↓2 | Blood fluids | In the absence of anti-T2D treatment, alteration of choline metabolism (increased degradation) noticed in T2D patients may result from: (a) an altered demand, possibly by altered lipoprotein turnover/biosynthesis, (b) an altered gut microbiotal activity associated with T2D development, or (c) an osmotic compensation for raised blood glucose concentrations. Low levels of choline would also associate to the prevalence of OB/T2D complications, namely nonalcoholic fatty liver. When associated with metformin, may indicate a possible two-way relationship between the anti-T2D treatment and the gut microbiota. The intestinal bacteria composition would influence glucose metabolism and the mechanisms of action of metformin, and the drug would regulate back the gut microbial function. | Zhang et al., 2009 | Firmicutes, Proteobacteria and Actinobacteria4 | |
| TMAO | Obesity + T2D | aaa | Blood fluids | Huo et al., 2009 | ||||
| DMA, DMG | Obesity + T2D | aaa | Urine | Salek et al., 2007 | ||||
| N-methylnicotinate (trigonelline) | Obesity + (pre-)T2D | ↓ | Urine | Gut microbial class-specific product of the metabolism of niacin, which is an essential vitamin involved in major physiological functions such as coenzyme in tissue respiration, carbohydrate and lipid metabolism. Trigonelline regenerates glutathione stores that are depleted by oxidative stress in obesity. Moreover, low levels of trigonelline could suggest perturbation in nucleotide metabolism during T2D. | Salek et al., 2007; Calvani et al., 2010 | NA | ||
| Organic acids and derivates | 2-hydroxyisobutyric acid | Obesity + pre-T2D | aaa | Urine | Since their production is species specific at the colonic level, changes in their level may reflect (a) significant shifts in the subjects’ gut microbe ecology or functional differences in the microbiome metabolic activity between OB with IR and healthy lean individuals and (b) changes in the host metabolism/uptake of gut-derived metabolites, possibly related to a variation in the intestinal mucosa permeability after weight-loss plan with calorie restriction and exercise. | Calvani et al., 2010 | Firmicutes5 | |
| tricarballylic acid | Obesity + pre-T2D | aaa | Blood fluids | Campbell et al., 2014 | ||||
| Phytochemical and purine metabolites | hippuric acid | Obesity + (pre-)T2D | ↓↓↓↓ | aaa | Urine | Changes in the production of hippurate and derivatives are generally connected to diet and gut microbial activities with the human metabolic phenotype and the blood pressure of individuals. They could indicate a relevant role of the gut microbiota in the pathogenesis of the pre-T2D state and could be related to age progression and gender effects on metabolism in T2D. The reversion of these changes by sulfonylurea treatment would confirm a beneficial effect of anti-T2D drugs on gut microbiota metabolism, besides glucose homeostasis. Higher concentrations in obese humans could reflect the known role of gut microbiota in energy metabolism and immune function of the host. | Salek et al., 2007; Calvani et al., 2010; Zhao et al., 2010; Huo et al., 2015 | Firmicutes5 |
| 3-Hippuric acid hydroxyhippuric acid | Urine | Zhao et al., 2010 | ||||||
| Methyluric acid | Obesity + pre-T2D | ↓ | Urine | Gut microbiota-associated metabolite biomarkers, related to IGT. Accumulating evidence indicates that the gut microbiota is instrumental in the energy metabolism and immune function of the host. | Zhao et al., 2010 | NA | ||
| Methylxanthine | Obesity + pre-T2D | ↓ | Urine | Zhao et al., 2010 | ||||
OB, obesity; T2D, type 2 diabetes; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; SU, sulfonylurea; M, metformin hydrochloride; TMAO, trimethylamine-N-oxide; NMN, oxN-methylnicotinate; DMG, N, N dimethylglycine; DMA, dimethylamine. 1In respect to healthy controls. 2Also in T2D vs. IGT but not IGT vs. NGT. 3From: Begley et al., 2005; Ridlon et al., 2006; Fukiya et al., 2009; Labbé et al., 2014. 4From: Craciun and Balskus, 2012. 5From: Li et al., 2008.