New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL͞6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1؊͞؊ animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host.symbiosis ͉ nutrient processing ͉ energy storage ͉ adiposity ͉ fastinginduced adipose factor

The metabolism of hyaluronan (HA) relies on HA synthases and hyaluronidases, among which hyaluronidase-1 (HYAL1) and -2 (HYAL2) have been proposed as key actors. Congenital HYAL1 deficiency leads to mucopolysaccharidosis IX (MPS IX), a rare lysosomal storage disorder characterized by joint abnormalities. Knowledge of HYAL2 is limited. This protein displays weak in vitro hyaluronidase activity and acts as a receptor for oncogenic ovine retroviruses. We have generated HYAL2-deficient mice through a conditional Cre-lox system. Hyal2(-/-) mice are viable and fertile. They exhibit localized congenital defects in frontonasal and vertebral bone formation and suffer from mild thrombocytopenia and chronic, possibly intravascular, hemolysis. In addition, Hyal2(-/-) mice display 10-fold increases in plasma levels of HA and 2-fold increases in plasma hyaluronidase activity. Globally, there is no HA accumulation in tissues, including bones, but liver sinusoidal cells seem overloaded with undigested HA. Taken together, these elements demonstrate for the first time that murine HYAL2 has a physiological activity in vivo that is relevant for craniovertebral bone formation, maintenance of plasma HA concentrations, and erythrocyte and platelet homeostasis. In addition, the viability of HYAL2-deficient mice raises the possibility that a similar defect, defining a new MPS disorder, exists in humans.

This study explored the effect of dietary xylo-oligosaccharide (XOS) supplementation on the gut microbial composition and activity in pigs of different ages. Eighty pigs with an average body weight (BW) of 30 kg were randomly divided into eight groups: A control group, a group that received antibiotic treatment, and six groups fed diets supplemented with 100, 250, and 500 g/t XOS, of which three groups were in the growing period (GP, 30–65 kg BW) and three groups in the growing and fattening period (GFP, 30–100 kg BW). At the end of the experiment, the intestinal contents were sampled for analyses of gut microbiota and bacterial metabolites including short-chain fatty acids (SCFAs) and bioamines. The results showed that 100 g/t XOS supplementation during the GFP significantly reduced the relative abundances of presumably pathogenic bacteria ( Proteobacteria and Citrobacter ), but enhanced the relative abundances of likely beneficial bacteria ( Firmicutes and Lactobacillus ). However, XOS supplementation during the GP showed little effect on the gut microbiota when pigs were killed at 100 kg BW. Meanwhile, 100 g/t XOS supplementation during the GFP decreased the level of 1,7-heptane diamine and increased the acetic acid, straight-chain fatty acids, and total SCFAs concentrations in the intestinal contents. Statistical analysis showed that both the dose and exposure time to XOS supplementation affected the microbial communities. In summary, 100 g/t XOS supplementation during the GFP modified the gut microbiota composition and metabolic activity. Possible consequences of such changes for the host are discussed.