Ning Ma

The intestinal homeostasis is an orchestrated dynamic equilibrium state composed of the coexistence and interactions among the nutrients, microbial flora, and immune system. The intestinal balance disorder can trigger a series of diseases, such as inflammatory bowel disease (IBD). Many of tryptophan (Trp) metabolites, such as kynurenine and indole, generated under a series of endogenous enzymes or microbial metabolism, have been reported enable to bind and activate the aryl hydrocarbon receptor (AhR), this series of process is termed the Trp-AhR pathway. The activated Trp-AhR pathway can induce the expression of downstream cytokines such as interleukin-22 (IL-22) and interleukin-17 (IL-17), thereby regulating the intestinal homeostasis. This review highlights the advance of Trp-AhR pathway in the regulation of intestinal homeostasis and provides some insights for the clinical strategies that expect to effectively prevent and treat gut diseases via intervening the Trp-AhR pathway.

The proinflammatory cytokine IL-1beta plays an important role in antifungal immunity; however, the mechanisms by which fungal pathogens trigger IL-1beta secretion are unclear. In this study we show that infection with Candida albicans is sensed by the Nlrp3 inflammasome, resulting in the subsequent release of IL-1beta. The ability of C. albicans to switch from a unicellular yeast form into a filamentous form is essential for activation of the Nlrp3 inflammasome, as C. albicans mutants incapable of forming hyphae were defective in their ability to induce macrophage IL- 1beta secretion. Nlrp3-deficient mice also demonstrated increased susceptibility to infection with C. albicans, which is consistent with a key role for Nlrp3 in innate immune responses to the pathogen C. albicans.

Dietary amino acids (AAs) are not only absorbed and metabolized by enterocytes but also available to the microbiota in the gut in mammals. In addition to serving as the materials for protein synthesis, AAs can act as precursors for numerous metabolic end products in reactions involving the intestinal mucosa and microbiota. After penetrating the epithelial barrier, microbial metabolites can enter and accumulate in the host circulatory system, where they are sensed by immune cells and then elicit a wide range of biological functions via different receptors and mechanisms. Some intestinal bacteria can also synthesize certain AAs, implying that the exchange of AAs between hosts and microorganisms is bidirectional. Changes in AA composition and abundance can affect AA-metabolizing bacterial communities and modulate macrophages and dendritic cells via toll-like receptors (TLRs), autoinducer-2 (AI-2), and NOD-like receptors (NLRs), and also regulate the gut-microbiome-immune axis via aryl hydrocarbon receptor (AhR), serotonin/5-hydroxytryptamine (5-HT), and other signaling pathways, all of which play critical roles in regulating the intestinal mucosal immunity and microbiota directly or indirectly, contributing to intestinal homeostasis. Therefore, the current findings of the effects of certain functional AAs on the gut-microbiome-immune axis are reviewed, illustrating signaling pathways of tryptophan (Trp), glutamine (Gln), methionine (Met), and branched-chain AAs (BCAAs) in the intestinal barrier and regarding immunity via crosstalk with their receptors or ligands. These findings have shed light on the clinical applications of dietary AAs in improving gut microbiota and mucosal immunity, therefore benefiting the gut as well as local and systemic health.

The intestine is the shared site of nutrient digestion, microbiota colonization and immune cell location and this geographic proximity contributes to a large extent to their interaction. The onset and development of a great many diseases, such as inflammatory bowel disease and metabolic syndrome, will be caused due to the imbalance of body immune. As competent assistants, the intestinal bacteria are also critical in disease prevention and control. Moreover, the gut commensal bacteria are essential for development and normal operation of immune system and the pathogens are also closely bound up with physiological disorders and diseases mediated by immune imbalance. Understanding how our diet and nutrient affect bacterial composition and dynamic function, and the innate and adaptive status of our immune system, represents not only a research need but also an opportunity or challenge to improve health. Herein, this review focuses on the recent discoveries about intestinal bacteria-immune crosstalk and nutritional regulation on their interplay, with an aim to provide novel insights that can aid in understanding their interactions.

There is growing recognition that composition and metabolic activity of the gut microbiota can be modulated by the dietary proteins which in turn impact health. The amino acid composition and digestibility of proteins, which are influenced by its source and amount of intake, play a pivotal role in determining the microbiota. Reciprocally, it appears that the gut microbiota is also able to affect protein metabolism which gives rise to the view that function between the microbiota and protein can proceed in both directions. In response to the alterations in dietary protein components, there are significant changes in the microbial metabolites including short chain fatty acids (SCFAs), ammonia, amines, gases such as hydrogen, sulfide and methane which are cytotoxins, genotoxins and carcinogens associated with development of colon cancer and inflammatory bowel diseases. A suitable ratio between protein and carbohydrate or even a low protein diet is recommended based on the evidence that excessive protein intake adversely affects health. Supplying high and undigested proteins will encourage pathogens and protein-fermenting bacteria to increase the risk of diseases. These changes of microbiota can affect the gut barrier and the immune system by regulating gene expression in relevant signaling pathways and by regulating the secretion of metabolites. The objective of this review is to assess the impact of dietary proteins on microbiota composition and activity in the gastrointestinal tract. Attention should be given to the dietary strategies with judicious selection of source and supplementation of dietary protein to benefit gut health.