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The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gut microbiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long-and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated.
Introduction: Intestinal bacteria influence gut morphology by affecting epithelial cell proliferation, development of the lamina propria, villus length and crypt depth [1]. Gut microbiota-derived factors have been proposed to also play a role in the development of a 30 % longer intestine, that is characteristic of PRM/Alf mice compared to other mouse strains [2, 3]. Polyamines and SCFAs produced by gut bacteria are important growth factors, which possibly influence mucosal morphology, in particular villus length and crypt depth and play a role in gut lengthening in the PRM/Alf mouse. However, experimental evidence is lacking. Aim: The objective of this work was to clarify the role of bacterially-produced polyamines on crypt depth, mucosa thickness and epithelial cell proliferation. For this purpose, C3H mice associated with a simplified human microbiota (SIHUMI) were compared with mice colonized with SIHUMI complemented by the polyamine-producing Fusobacterium varium (SIHUMI + Fv). In addition, the microbial impact on gut lengthening in PRM/Alf mice was characterized and the contribution of SCFAs and polyamines to this phenotype was examined. Results: SIHUMI + Fv mice exhibited an up to 1.7 fold higher intestinal polyamine concentration compared to SIHUMI mice, which was mainly due to increased putrescine concentrations. However, no differences were observed in crypt depth, mucosa thickness and epithelial proliferation. In PRM/Alf mice, the intestine of conventional mice was 8.5 % longer compared to germfree mice. In contrast, intestinal lengths of C3H mice were similar, independent of the colonization status. The comparison of PRM/Alf and C3H mice, both associated with SIHUMI + Fv, demonstrated that PRM/Alf mice had a 35.9 % longer intestine than C3H mice. However, intestinal SCFA and polyamine concentrations of PRM/Alf mice were similar or even lower, except N acetylcadaverine, which was 3.1-fold higher in PRM/Alf mice. When germfree PRM/Alf mice were associated with a complex PRM/Alf microbiota, the intestine was one quarter longer compared to PRM/Alf mice colonized with a C3H microbiota. This gut elongation correlated with levels of the polyamine N acetylspermine. Conclusion: The intestinal microbiota is able to influence intestinal length dependent on microbial composition and on the mouse genotype. Although SCFAs do not contribute to gut elongation, an influence of the polyamines N acetylcadaverine and N acetylspermine is conceivable. In addition, the study clearly demonstrated that bacterial putrescine does not influence gut morphology in C3H mice.