Interaction between Gut Microbiota and Toll-like Receptor: from Immunity to Metabolism

The human gut contains trillions of commensal bacteria, and similar to pathogenic bacteria, the gut microbes and their products can be recognized by toll-like receptors (TLRs). It is well acknowledged that the interaction between gut microbiota and the local TLRs help to maintain the homeostasis of intestinal immunity. High-fat intake or obesity can weaken gut integrity leading to the penetration of gut microbiota or their bacterial products into the circulation, leading to the activation of TLRs on immune cells and subsequently low-grade systemic inflammation in host. Metabolic cells including hepatocytes and adipocytes also express TLRs. Although they are able to produce and secrete inflammatory molecules, the effectiveness remains low compared with the immune cells embedded in liver and adipose tissue. The interaction of TLRs in these metabolic cells or organs with gut microbiota remains unclear, but a few studies have suggested that the functions of these TLRs are related to metabolism. Alteration of the gut microbiota is associated with body weight change and adiposity in human, and the interaction between the commensal gut microbiota and TLRs may possibly involve both metabolic and immunological regulation. In this review, we will summarize the current findings on the relationship between TLRs and gut microbiota with a focus on metabolic regulation, and discuss how such interaction participates in host metabolism.published_or_final_versio

Gut microbiome - Our life partner, for better or worse?

3.4 Food: The key to health and wellbeing - Oral Presentation no. 178Trillions of bacteria are living in our bodies and implementing mutualistic functions to us. The gastrointestinal tract alone houses more than 1014 bacteria. One of their known functions is to promote energy extraction from our diets, thereby allowing us to better utilize our food source, particularly in nutrient-scarce environments. This function plays an important role during pregnancy when extra nutrients are needed for the development of the fetus. [Before birth] Substantial changes in the bacterial pattern in the gut have been found in pregnant women from the 1st to 3rd trimesters. This kind of commensalism remains despite the agricultural advances in that have led to a stable nutritional supply, which implies some additional functions of the gut bacteria in pregnancy. Due to the advance of medicine, now we have choices in the modes of delivery. However, cesarean section-delivered babies have a higher risk to develop certain metabolic and autoimmune diseases in early childhood. [At birth] Such risk is related to the differences in bacteria colonization upon different modes of delivery. [After birth] During adulthood, our diet and external environment can substantially change the gut microbiota. Many animal models have proven the effectiveness of fecal transplantation to reverse several diseases, implying the therapeutic potential of altering gut microbiota. However, bed-translation remains limited due to the complicated bacterial ecology and cross-species interaction with host. Investigation from the very beginning of life will help us gain a full picture of how we interact with these commensal microorganisms, thus affecting our health

Involvement of toll-like receptor 5 pathway in hepatic lipid export

Conference Theme: Frontiers in Human Microbiota Symbiotic Interaction

Regulation of adipogenesis by toll-like receptor 5 pathway

Toll-like receptor 5 (TLR5) recognizes the bacterial product, flagellin. Its activation leads to cytokine production that is important for host defense against invading pathogens. In spite of the pro-inflammatory nature of TLR5, deficiency of TLR5 exacerbated metabolic dysfunction in diet-induced obese mouse model (Gewirtz et al. Science, 328: 228-231, 2010). In this study, we found that TLR5 was expressed in both preadipocytes and adipocytes, and tried to characterize the functions of TLR5 in these metabolic cells Six week old wild type (WT) and TLR5-knockout (T5KO) mice were fed a high fat diet for five weeks, andthey both showed a similar body weight gain and daily food intake, but NMR spectroscopy revealed a decreased whole-body fat mass in T5KO mice. Particularly, gonadal adipose tissues in T5KO mice were significantly smaller compared with those in WT, whereas the adipose inflammatory status was unaltered. The in vitro experiments showed that TLR5-deficient stromal vascular cells isolated from visceral fat depots had reduced adipogenic capacity. In addition, elevated triglyceride accumulation was observed in livers from T5KO mice. iIt is possible that TLR5 pathway participates in adipogenesis to mediate adipose tissue expansion and prevents ectopic storage of lipids in liver after high fat diet feeding. It is noteworthy to further explore the possible direct functions of TLR5 in metabolic cells

Regulation of adipogenesis in visceral adipose tissue by toll-like receptor 5 pathway

Conference Theme: Science and Aging: An Era of Discover

Metabolic function of toll like receptor mediated by TRIF

Conference Theme: Nutritional Immunology: Role in Health and Diseas

TRIF-dependent Toll-like receptor signaling suppresses Scd1 transcription in hepatocytes and prevents diet-induced hepatic steatosis

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases that ranges in severity from hepatic steatosis to steatohepatitis, the latter of which is a major predisposing factor for liver cirrhosis and cancer. Toll-like receptor (TLR) signaling, which is critical for innate immunity, is generally believed to aggravate disease progression by inducing inflammation. Unexpectedly, we found that deficiency in TIR domain-containing adaptor-inducing interferon-β (TRIF), a cytosolic adaptor that transduces some TLR signals, worsened hepatic steatosis induced by a high-fat diet (HFD) and that such exacerbation was independent of myeloid cells. The aggravated steatosis in Trif-/- mice was due to the increased hepatocyte transcription of the gene encoding stearoyl-coenzyme A (CoA) desaturase 1 (SCD1), the rate-limiting enzyme for lipogenesis. Activation of the TRIF pathway by polyinosinic:polycytidylic acid [poly(I:C)] suppressed the increase in SCD1 abundance induced by palmitic acid or an HFD and subsequently prevented lipid accumulation in hepatocytes. Interferon regulatory factor 3 (IRF3), a transcriptional regulator downstream of TRIF, acted as a transcriptional suppressor by directly binding to the Scd1 promoter. These results suggest an unconventional metabolic function for TLR/TRIF signaling that should be taken into consideration when seeking to pharmacologically inhibit this pathway