Interactions between gut microbial metabolites and host immune cells (IMAGE)
Caption
Gut microbiota-derived metabolites, including bile acids, SCFAs, and amino acid-derived metabolites (here mainly referring to tryptophan metabolites), can interact with the host innate and adaptive immune systems and thereby broadly participate in the regulation of physiological and pathophysiological processes. In innate immunity, different microbiota-derived tryptophan metabolites modulate neutrophil functions to alleviate intestinal①inflammatory responses, while under specific contexts they may also exacerbate lung②tissue injury. In the context of hepatocellular carcinoma③, SCFAs (such as butyrate) or bile acids (such as glycolithocholic acid, GLCA) influence host antitumor immune responses by regulating NK cell function. SCFAs and bile acids (such as taurodeoxycholic acid, TDCA, and glycoursodeoxycholic acid, GUDCA) can alleviate intestinal inflammation by modulating the functions of ILCs, whereas GDCA can also improve PCOS④-associated metabolic and inflammatory phenotypes via ILC3. With respect to DCs, SCFAs can promote tumor growth by suppressing their antigen-presenting capacity, while bile acids (such as deoxycholic acid, DCA, and chenodeoxycholic acid, CDCA) alleviate host autoimmune inflammation and intestinal inflammation by regulating DCs function. In addition, microbiota-derived TMAO can induce trained innate immunity and antitumor immune responses in macrophage, thereby enhancing host resistance to tuberculosis and antitumor immune responses against pancreatic⑥cancer. In adaptive immunity, gut microbiota-derived bile acids (such as 3-oxoLCA and isoalloLCA), folate, SCFAs, and indole derivatives can alleviate intestinal inflammation and skin⑤diseases by regulating the balance between Th17 cells and regulatory T cells (Tregs) among CD4+ T cells. For CD8+ T cells, bile acids (such as DCA, 3-oxo-Δ4,6-LCA, and taurocholic acid, TCA) as well as SCFAs can influence host antitumor immune responses, inflammatory processes, and respiratory tract⑦infection-associated pathological manifestations by modulating their effector functions. In addition, SCFAs and indole derivatives can also affect host anti-infective immunity and local inflammatory responses, such as central nervous system⑧inflammation and autoimmune responses, by regulating B cell function. Abbreviations: NRs: nuclear receptors; MRs: membrane receptors; TFs: transcription factors; IAA: indole-3-acetic acid; IPA: indole-3-propionic acid; I3S: indoxyl sulfate; ICA: indole-3-carboxaldehyde; C1: formic acid; C2: acetic acid; C3: propionic acid; C4: butyric acid; CSR: class switch recombination
Credit
Professor Changtao Jiang from Peking University, Beijing, China Image source link: https://link.springer.com/article/10.1007/s44466-026-00031-7
Usage Restrictions
Credit must be given to the creator. Only noncommercial uses of the work are permitted. No derivatives or adaptations of the work are permitted.
License
CC BY-NC-ND