Diet-Induced Alterations of Host Cholesterol Metabolism Are Likely To Affect the Gut Microbiota Composition in Hamsters

Abstract

The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota.T he mammalian gastrointestinal tract is colonized by trillions of microorganisms (the gut microbiota), a large fraction of which are bacteria. This microbial community has an extensive impact on host metabolism with important implications for health (1-3). The contribution of the gut microbiota to energy harvest from the diet and to fat storage constitutes a key beneficial trait that underlies host-microbiota symbiosis in mammals (4). However, this contribution has likely become detrimental to modern humans living in societies with excess food resources, as it increases susceptibility to metabolic disorders, such as obesity, type 2 diabetes, and coronary heart disease. Accordingly, the gut microbiota is increasingly being accepted as an important factor that contributes to pathological conditions associated with obesity (5), and in humans, metabolic pathologies often are associated with alterations in the gut microbiota (which is referred to as dysbiosis) (6-9). Unfortunately, there is still little consensus on the bacterial groups that are linked to obesity-related diseases and metabolic phenotypes (3). In addition, although comparisons between germ-free and conventional mice and rats have clearly established a role of the microbiota in modulating host lipid metabolism (2, 10-12), it remai...

Prebiotics, gut microbiota and metabolic risks: Unveiling the relationship

“…They inferred that HPMC is a potential prebiotic that influenced gut microbiota and improved the host metabolism. Later, Martínez et al (2013) unravel the association of faecal microbiota with cholesterol reduction in hamsters. They proposed that diet based therapy comprising plant sterol esters extensively modulated the cholesterol metabolism, reducing the level of different bacterial taxa within Coriobacteriaceae and Erysipelotrichaceae.…”

Patterns of seasonality and group membership characterize the gut microbiota in a longitudinal study of wild Verreaux's sifakas (Propithecus verreauxi)

“…Coriobacteriaceae were positively associated with liver triglyceride levels and serum cholesterol levels and negatively associated with liver glucose and glycogen levels in laboratory rodents (Claus et al., 2011). Additionally, cholesterol excreted in bile had antibacterial effects on Coriobacteriaceae (Martínez et al., 2013). Thus, an increase in endogenous lipid metabolism and/or a decrease of fecal cholesterol excretion in sifakas during the dry season could cause the increase in Coriobacteriaceae.…”

Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans

“…These taxa have been described to play a role in hepatic lipid metabolism in rodents and fatty liver development in humans and to be SCFA producers in the presence of high-fat and high-glucose diet, but limited data are available. 65-67 …”