Mechanisms linking gut microbial metabolites to insulin resistance

Insulin resistance is the rate-limiting step in the development of metabolic diseases,including type 2 diabetes.The gut microbiota has been implicated in host energy metabolism and metabolic diseases and is recognized as a quantitatively important organelle in host metabolism,as the human gut harbors 10 trillion bacterial cells.Gut microbiota break down various nutrients and produce metabolites that play fundamental roles in host metabolism and aid in the identification of possible therapeutic targets for metabolic diseases.Therefore,understanding the various effects of bacterial metabolites in the development of insulin resistance is critical.Here,we review the mechanisms linking gut microbial metabolites to insulin resistance in various insulin-responsive tissues.

Salmonella Typhimurium infection disrupts but continuous feeding of Bacillus based probiotic restores gut microbiota in infected hens

Background:The gut microbiota plays an important role in the colonisation resistance and invasion of pathogens.Salmonella Typhimurium has the potential to establish a niche by displacing the microbiota in the chicken gut causing continuous faecal shedding that can result in contaminated eggs or egg products.In the current study,we investigated the dynamics of gut microbiota in laying chickens during Salmonella Typhimurium infection.The optimisation of the use of an infeed probiotic supplement for restoration of gut microbial balance and reduction of Salmonella Typhimurium load was also investigated.Results:Salmonella infection caused dysbiosis by decreasing(FDR<0.05)the abundance of microbial genera,such as Blautia,Enorma,Faecalibacterium,Shuttleworthia,Sellimonas,Intestinimonas and Subdoligranulum and increasing the abundance of genera such as Butyricicoccus,Erysipelatoclostridium,Oscillibacter and Flavonifractor.The higher Salmonella Typhimurium load resulted in lower(P<0.05)abundance of genera such as Lactobacillus,Alistipes,Bifidobacterium,Butyricimonas,Faecalibacterium and Romboutsia suggesting Salmonella driven gut microbiota dysbiosis.Higher Salmonella load led to increased abundance of genera such as Caproiciproducens,Acetanaerobacterium,Akkermansia,Erysipelatoclostridium,Eisenbergiella,EscherichiaShigella and Flavonifractor suggesting a positive interaction of these genera with Salmonella in the displaced gut microbiota.Probiotic supplementation improved the gut microbiota by balancing the abundance of most of the genera displaced by the Salmonella challenge with clearer effects observed with continuous supplementation of the probiotic.The levels of acetate and butyrate in the faeces were not affected(P>0.05)by Salmonella challenge and the butyrate level was increased by the continuous feeding of the probiotic.Probiotic supplementation in Salmonella challenged chickens resulted in higher level of propionate.Continuous probiotic supplementation decreased(P<0.05)the overall mean load of Salmonella in faeces and had a significant effect on Salmonella load reduction in internal organs.Conclusions:Salmonella challenge negatively impacts the diversity and abundance of many gut microbial genera involved in important functions such as organic acid and vitamin production.Strategic feeding of a Bacillus based probiotic helps in restoring many of the microbial genera displaced by Salmonella Typhimurium challenge.

The role of gut microbiota associated metabolites in digestive disorders

The gut has been a focal point in the research of digestive system disorders.The internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and influ-encing host physiology and pathology.Besides,the gut microbiota and metabolites owe highly diverse types and quantities,posing challenges for quantitative analysis,and monitoring frequent interactions between diges-tive tract metabolites and the intestinal wall remains a challenge.However,research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases.By modulating metabolites such as short-chain fatty acids,bile acids,and lipopolysaccharides,it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease.Currently,research on gut microbiota is advancing,and more work is required to explore the interactions between host,microbes and underlying mech-anisms.In this review,we have revisited the generation of gut microbiota-related metabolites,their impact on diseases,and modes of interaction,emphasizing the significant role of metabolites in digestive system disorders.It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites,providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

Mesenteric lymph system constitutes the second route in gut-liver axis and transports metabolism-modulating gut microbial metabolites

The gut-liver axis denotes the intricate connection and interaction between gut microbiome and liver, in which compositional and functional shifts in gut microbiome affect host metabolism. Hepatic portal vein of the blood circulation system has been thought to be the major route for metabolite transportation in the gut-liver axis, but the existence and importance of other routes remain elusive. Here, we perform metabolome comparison in blood circulation and mesenteric lymph systems and identify significantly shifted metabolites in serum and mesentery. Using cellular assays, we find that the majority of decreased metabolites in lymph system under high-fat diet are effective in alleviating metabolic disorders, indicating a high potential of lymph system in regulating liver metabolism. Among those, a representative metabolite, L-carnitine, reduces diet-induced obesity in mice. Metabolic tracing analysis identifies that L-carnitine is independently transported by the mesenteric lymph system, serving as an example that lymph circulation comprises a second route in the gut-liver axis to modulate liver metabolism. Our study provides new insights into metabolite transportation via mesenteric lymph system in the gut-liver axis, offers an extended scope for the investigations in host-gut microbiota metabolic interactions and potentially new targets in the treatment of metabolic disorders.