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.

Microbiota of the gastrointestinal tract: Friend or foe?

The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection.The gut microbiota encodes over 3 million genes,which is approximately 150 times more than the total number of genes present in the human genome.Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites,changes in intestinal barrier function,and inflammation and can cause the development of a wide variety of diseases,such as diabetes,obesity,gastrointestinal disorders,cardiovascular issues,neurological disorders and oncological concerns.In this review,I consider issues related to the role of the microbiome in the regulation of intestinal barrier function,its influence on physiological and pathological processes occurring in the body,and potential new therapeutic strategies aimed at restoring the gut microbiome.Herewith,it is important to understand that the gut microbiota and human body should be considered as a single biological system,where change of one element will inevitably affect its other components.Thus,the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors,the role of which has not yet been fully elucidated.

Genetic heterogeneity of colorectal cancer and the microbiome

In 2020,the International Agency for Research on Cancer and the World Health Organization's GLOBOCAN database ranked colorectal cancer(CRC)as the third most common cancer in the world.Most cases of CRC(>95%)are sporadic and develop from colorectal polyps that can progress to intramucosal carcinoma and CRC.Increasing evidence is accumulating that the gut microbiota can play a key role in the initiation and progression of CRC,as well as in the treatment of CRC,acting as an important metabolic and immunological regulator.Factors that may determine the microbiota role in CRC carcinogenesis include inflammation,changes in intestinal stem cell function,impact of bacterial metabolites on gut mucosa,accumulation of genetic mutations and other factors.In this review,I discuss the major mechanisms of the development of sporadic CRC,provide detailed characteristics of the bacteria that are most often associated with CRC,and analyze the role of the microbiome and microbial metabolites in inflammation initiation,activation of proliferative activity in intestinal epithelial and stem cells,and the development of genetic and epigenetic changes in CRC.I consider longterm studies in this direction to be very important,as they open up new opportunities for the treatment and prevention of CRC.

Oat bran and wheat bran impact net energy by shaping microbial communities and fermentation products in pigs fed diets with or without xylanase

Background: Dietary fiber can be fermented in gut of pigs and the end products of fermentation were short-chain fatty acids(SCFA). The SCFA had positive effects on gut bacteria and host immune system. In addition, SCFA can provide a part of available energy for pigs. However, there were limited reports on the relationship between dietary fiber, gut bacteria, and energy metabolism. Therefore, this study investigated how dietary fiber and enzyme addition impacted energy metabolism by acting on the microbial community and SCFA.Methods: Wheat bran(WB) was added to the corn-soybean meal-based diet at the levels of 12% and 27%, and oat bran(OB) at 15% and 36%. One of each diet was supplemented with or without 5000 U/kg feed of xylanase, so a total of 10 diets were allotted to 60 growing pigs(initial body weight: 27.2 ± 1.2 kg) using a randomized complete block design. The experiment was conducted in 10 consecutive periods using 6 similar open-circuit respiration chambers. Each pig was used for one 20-day period. During each period, six pigs were allowed 14 d to adapt to the diets in metabolic cages followed by 6 d(from d 15 to d 20) in respiration chambers to measure heat production(HP).Results: Pigs fed 36% OB diets had greater(P < 0.05) nutrient digestibility and net energy(NE) values compared to those fed 27% WB diets. Apparent digestibility coefficients of dry matter(DM) and crude protein(CP) were lower(P < 0.05) in pigs fed 27% WB diets compared with those fed 12% WB diets. Enzyme addition improved(P < 0.05)the NE values(11.37 vs. 12.43 MJ/kg DM) in diets with 27% WB. Supplementation of xylanase did not affect NE values for basal diets, OB diets and 12%WB diets. Compared with diets with 36% OB, pigs fed 27% WB-based diets excreted more total SCFA, acetate and propionate(expressed as g/kg feed DM) in fecal samples of pigs(P < 0.05).Pigs in the WB diets had greater proportion of phylum Bacteroidetes while phylum Firmicutes were greater in pigs fed OB diets(P < 0.05). Pigs fed WB diets had greater(P < 0.05) abundance of Succinivibrio and Prevotella, which were associated with fiber degradation and SCFA production.Conclusion: Our results indicated diets supplied by high level of OB or WB promote the growth of fiber-degrading bacteria. The differences in fiber composition between WB and OB led to differences in nutrient digestibility and bacterial communities, which were ultimately reflected in energy metabolism. Enzyme supplementation improved nutrient digestibility as well as NE values for 27% WB diets but not for other diets, which indicated that effects of enzyme were related to type and level of dietary fiber in diets.

Fate of undigested proteins in the pig large intestine:What impact on the colon epithelium?

Apart from its obvious agronomic interest in feeding billions of people worldwide,the porcine species represents an irreplaceable experimental model for intestinal physiologists and nutritionists.In this review,we give an overview on the fate of proteins that are not fully digested in the pig small intestine,and thus are transferred into the large intestine.In the large intestine,dietary and endogenous proteins are converted to peptides and amino acids(AA)by the action of bacterial proteases and peptidases.AA,which cannot,except in the neonatal period,be absorbed to any significant level by the colonocytes,are used by the intestinal microbes for protein synthesis and for the production of numerous metabolites.Of note,the production of the AA-derived metabolites greatly depends on the amount of undigested polysaccharides in the pig's diet.The effects of these AA-derived bacterial metabolites on the pig colonic epithelium have not yet been largely studied.However,the available data,performed on colonic mucosa,isolated colonic crypts and colonocytes,indicate that some of them,like ammonia,butyrate,acetate,hydrogen sulfide(H_(2)S),and p-cresol are active either directly or indirectly on energy metabolism in colonic epithelial cells.Further studies in that area will certainly gain from the utilization of the pig colonic organoid model,which allows for disposal of functional epithelial unities.Such studies will contribute to a better understanding of the potential causal links between diet-induced changes in the luminal concentrations of these AA-derived bacterial metabolites and effects on the colon epithelial barrier function and water/electrolyte absorption.

Use of 25-hydroxyvitamin D_(3) in diets for sows:A review

Dietary supplementation with 25-hydroxyvitamin D_(3)(25OHD_(3)),as an alternative source of vitamin D,is becoming increasingly popular due to its commercialization and more efficient absorbability.The addition of 25OHD_(3)rather than its precursor vitamin D_(3)can circumvent the 25-hydroxylation reaction in the liver,indicating that supplementation of 25OHD_(3)can rapidly improve the circulating vitamin D status of animals.Emerging experiments have reported that maternal 25OHD_(3)supplementation could increase sow performances and birth outcomes and promote circulating vitamin D status of sows and their offspring.Increased milk fat content was observed in many experiments;however,others demonstrated that adding 25OHD_(3)to lactating sow diets increased the contents of milk protein and lactose.Although an inconsistency between the results of different experiments exists,these studies suggested that maternal 25OHD_(3)supplementation could alter milk composition via its effects on the mammary gland.Previous studies have demonstrated that adding 25OHD_(3)to sow diets could improve the mRNA expressions of insulin-induced gene 1(INSIG1)and sterol regulatory element-binding protein 1(SREBP1)in the mammary gland cells from milk and increase the mRNA expressions of acetyl-CoA carboxylaseα(ACCα)and fatty acid synthase(FAS)in the mammary gland tissue.Maternal 25OHD_(3)supplementation promotes skeletal muscle development of piglets before and after parturition,and improves bone properties including bone density and bone breaking force in lactating sows and their piglets.Interestingly,25OHD_(3)supplementation in sow diets could improve neonatal bone development via regulation of milk fatty acid composition related to bone metabolism and mineralization.In this review,we also discuss the effects of adding 25OHD_(3)to sow diets on the gut bacterial metabolites of suckling piglets,and propose that butyrate production may be associated with bone health.Therefore,to better understand the nutritional functions of maternal 25OHD_(3)supplementation,this paper reviews advances in the studies of 25OHD_(3)for sow nutrition and provides references for practical application.