Microbiome-modulated metabolites at the interface of host immunity
Open accessAbstract
The mammalian gastrointestinal tract and associated mucosal immune system harbor a large repertoire of metabolites of prokaryotic and eukaryotic origin that play important roles in eukaryotic development and physiology. These often bioactive small molecules originate from nutrition- and environmental-related sources, or are endogenously produced and modulated by the host and its microbiota. A complex network of interactions exists between the intestinal mucosal immune system and the microbiota. This intimate cross-talk may be driven by metabolite secretion and signaling, and features profound influences on host immunity and physiology, including the endocrine, metabolic, and nervous system function in health and disease. Alterations in microbiome-associated metabolite levels and activity are implicated in the pathogenesis of a growing number of illnesses. In this review we discuss the origin and influence of microbiome-modulated metabolites, with an emphasis on immune cell development and function. We further highlight the emerging data potentially implicating metabolite misbalance with host-microbiome–associated disease.
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Pathway enrichment comparisons showed anabolic functions predominating in responders including amino acid biosynthesis, and catabolic functions predominating in non-responders.
“Comparisons of pathway enrichment across these groups showed changes in metabolic functions, with anabolic functions predominating in R including amino acid biosynthesis (Fig. 3E), which may promote host immunity (36), whereas catabolic functions predominated in NR (Fig. 3E, fig. S16, and table S7).”
From Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients (2018) · cites this paper as [36]
The citation is attached to the suggestion that amino acid biosynthesis may promote host immunity, not to the responder/non-responder comparison, which the citing sentence assigns to its own figures. In “Microbiome modulation of the gastrointestinal metabolite configuration” (page unavailable), the source describes tryptophan as immunomodulatory, but it does not establish that amino acid biosynthesis itself promotes immunity. (LLM, conf=0.78)
Experimental — accuracy not yet measuredSeveral microbial metabolites, such as taurine, spermine, and histamine, can affect NLRP6 inflammasome activation in the gut and play an important role, if properly balanced, in host-microbial mutualism at the level of the intestine.
“Several microbial metabolites, such as taurine, spermine, and histamine, can affect the NLRP6 inflammasome activation in the gut and play an important role, if properly balanced, in host-microbial mutualism at the level of the intestine (213).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [213]
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- Authors
- Blacher, E., Levy, M., Tatirovsky, E., & Elinav, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Elinav, Eran
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-01
- Volume
- 198
- Issue
- 2
- Pages
- 572-580
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2579549256
- Semantic Scholar
- 4ba983acb6e75172fe600b653ca34cf7146c9135
- Cited by
- 354
- References
- 99
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 36 · 2023: 38 · 2022: 61 · 2021: 51 · 2020: 50 · 2019: 39 · 2018: 23 · 2017: 12
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- Canadian Institute for Advanced Research
- European Foundation for the Study of Diabetes
- Minerva Foundation
- German-Israeli Foundation for Scientific Research and Development
- Israel Science Foundation
- Abisch-Frenkel-Stiftung
- Rising Tide Foundation
- Benoziyo Endowment Fund for the Advancement of Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- gut microbiota, gut microbiota metabolites, intestinal mucosal immunity, host-microbiota interactions, immune cell development, immune cell function, metabolite signaling, endocrine function, metabolic function, nervous system
- MeSH terms
- Gastrointestinal Microbiome, Animals, Humans, Immune System, Immunity, Mucosal, Receptor Cross-Talk
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