Donia, M. S. & Fischbach, M. A. Small molecules from the human microbiota. Science 349, 1254766 (2015).
Krautkramer, K. A., Fan, J. & Backhed, F. Gut microbial metabolites as multi-kingdom intermediates. Nat. Rev. Microbiol. 19, 77–94 (2021).
Arpaia, N. et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504, 451–455 (2013).
Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).
Furusawa, Y. et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504, 446–450 (2013).
Hang, S. et al. Bile acid metabolites control TH17 and Treg cell differentiation. Nature 576, 143–148 (2019).
Song, X. et al. Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis. Nature 577, 410–415 (2020).
Campbell, C. et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature 581, 475–479 (2020).
Cervantes-Barragan, L. et al. Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells. Science 357, 806–810 (2017).
Song, X. et al. Gut microbial fatty acid isomerization modulates intraepithelial T cells. Nature 619, 837–843 (2023).
Mazmanian, S. K., Round, J. L. & Kasper, D. L. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453, 620–625 (2008).
Oh, S. F. et al. Host immunomodulatory lipids created by symbionts from dietary amino acids. Nature 600, 302–307 (2021).
Peterson, L. W. & Artis, D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat. Rev. Immunol. 14, 141–153 (2014).
Mukherjee, S. & Hooper, L. V. Antimicrobial defense of the intestine. Immunity 42, 28–39 (2015).
Wu, M. et al. Gut complement induced by the microbiota combats pathogens and spares commensals. Cell https://doi.org/10.1016/j.cell.2023.12.036 (2024).
Cash, H. L., Whitham, C. V., Behrendt, C. L. & Hooper, L. V. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313, 1126–1130 (2006).
Vaishnava, S. et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).
Bergstrom, J. H. et al. Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16. Proc. Natl Acad. Sci. USA 113, 13833–13838 (2016).
McPherson, R. L. et al. Lectin-Seq: a method to profile lectin-microbe interactions in native communities. Sci. Adv. 9, eadd8766 (2023).
Palm, N. W. et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell 158, 1000–1010 (2014).
Kau, A. L. et al. Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy. Sci. Transl. Med. 7, 276ra224 (2015).
Shapiro, J. M. et al. Immunoglobulin A targets a unique subset of the microbiota in inflammatory bowel disease. Cell Host Microbe 29, 83–93 e83 (2021).
Hooper, L. V. et al. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291, 881–884 (2001).
Geva-Zatorsky, N. et al. Mining the human gut microbiota for immunomodulatory organisms. Cell 168, 928–943 e911 (2017).
Sun, L. et al. Type I interferons link viral infection to enhanced epithelial turnover and repair. Cell Host Microbe 17, 85–97 (2015).
Kreit, M., Vertommen, D., Gillet, L. & Michiels, T. The interferon-inducible mouse apolipoprotein L9 and prohibitins cooperate to restrict Theiler’s virus replication. PLoS ONE 10, e0133190 (2015).
Haber, A. L. et al. A single-cell survey of the small intestinal epithelium. Nature 551, 333–339 (2017).
Wang, Y. et al. Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine. J. Exp. Med. https://doi.org/10.1084/jem.20191130 (2020).
Wexler, A. G. & Goodman, A. L. An insider’s perspective: Bacteroides as a window into the microbiome. Nat. Microbiol. 2, 17026 (2017).
Uzureau, S. et al. APOL1 C-terminal variants may trigger kidney disease through interference with APOL3 control of actomyosin. Cell Rep. 30, 3821–3836 e3813 (2020).
Brown, E. M. et al. Bacteroides-derived sphingolipids are critical for maintaining intestinal homeostasis and symbiosis. Cell Host Microbe 25, 668–680 e667 (2019).
Johnson, E. L. et al. Sphingolipids produced by gut bacteria enter host metabolic pathways impacting ceramide levels. Nat. Commun. 11, 2471 (2020).
Stankeviciute, G. et al. Convergent evolution of bacterial ceramide synthesis. Nat. Chem. Biol. 18, 305–312 (2022).
Dhakephalkar, T., Stukey, G. J., Guan, Z., Carman, G. M. & Klein, E. A. Characterization of an evolutionarily distinct bacterial ceramide kinase from Caulobacter crescentus. J. Biol. Chem. 299, 104894 (2023).
Heaver, S. L. et al. Characterization of inositol lipid metabolism in gut-associated Bacteroidetes. Nat. Microbiol. 7, 986–1000 (2022).
Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).
Perez-Morga, D. et al. Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes. Science 309, 469–472 (2005).
Thomson, R. & Finkelstein, A. Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: relevance to trypanosome lysis. Proc. Natl Acad. Sci. USA 112, 2894–2899 (2015).
Gaudet, R. G. et al. A human apolipoprotein L with detergent-like activity kills intracellular pathogens. Science https://doi.org/10.1126/science.abf8113 (2021).
Stefan, K. L., Kim, M. V., Iwasaki, A. & Kasper, D. L. Commensal microbiota modulation of natural resistance to virus infection. Cell 183, 1312–1324 e1310 (2020).
Yang, D. et al. Dysregulated lung commensal bacteria drive interleukin-17B production to promote pulmonary fibrosis through their outer membrane vesicles. Immunity 50, 692–706 e697 (2019).
Shen, Y. et al. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe 12, 509–520 (2012).
Heuberger, C., Pott, J. & Maloy, K. J. Why do intestinal epithelial cells express MHC class II? Immunology 162, 357–367 (2021).
Moon, S. et al. Niche-specific MHC II and PD-L1 regulate CD4+CD8αα+ intraepithelial lymphocyte differentiation. J. Exp. Med. https://doi.org/10.1084/jem.20201665 (2021).
Lockhart, A., Mucida, D. & Bilate, A. M. Intraepithelial lymphocytes of the intestine. Annu. Rev. Immunol. https://doi.org/10.1146/annurev-immunol-090222-100246 (2024).
Cullen, T. W. et al. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science 347, 170–175 (2015).
Garcia-Bayona, L. & Comstock, L. E. Streamlined genetic manipulation of diverse Bacteroides and Parabacteroides isolates from the human gut microbiota. mBio https://doi.org/10.1128/mBio.01762-19 (2019).
Sugiura, M. et al. Ceramide kinase, a novel lipid kinase. Molecular cloning and functional characterization. J. Biol. Chem. 277, 23294–23300 (2002).
Clarke, E. L. et al. Sunbeam: an extensible pipeline for analyzing metagenomic sequencing experiments. Microbiome 7, 46 (2019).
Kang, D. D. et al. MetaBAT 2: an adaptive binning algorithm for robust and efficient genome reconstruction from metagenome assemblies. PeerJ 7, e7359 (2019).
Parks, D. H., Imelfort, M., Skennerton, C. T., Hugenholtz, P. & Tyson, G. W. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res. 25, 1043–1055 (2015).
Lam, S. M. et al. A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19. Nat. Metab. 3, 909–922 (2021).
Yuan, X. et al. Identification of an endogenous ligand bound to a native orphan nuclear receptor. PLoS ONE 4, e5609 (2009).
Han, X., Yang, Y., Zhao, F., Zhang, T. & Yu, X. An improved protein lipid overlay assay for studying lipid-protein interactions. Plant Methods 16, 33 (2020).
Couter, C. J. & Surana, N. K. Isolation and flow cytometric characterization of murine small intestinal lymphocytes. J. Vis. Exp. https://doi.org/10.3791/54114 (2016).
Ivanov, I. I. et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485–498 (2009).
Hsu, C. C., Okumura, R. & Takeda, K. Human LYPD8 protein inhibits motility of flagellated bacteria. Inflamm. Regen. 37, 23 (2017).
Wang, Y. C. et al. Intestinal cell type-specific communication networks underlie homeostasis and response to Western diet. J. Exp. Med. https://doi.org/10.1084/jem.20221437 (2023).
Gilmore, W. J. et al. Bacteroides fragilis outer membrane vesicles preferentially activate innate immune receptors compared to their parent bacteria. Front. Immunol. 13, 970725 (2022).
Bousbaine, D. et al. A conserved Bacteroidetes antigen induces anti-inflammatory intestinal T lymphocytes. Science 377, 660–666 (2022).
Jiang, L. et al. Salmonella typhimurium reprograms macrophage metabolism via T3SS effector SopE2 to promote intracellular replication and virulence. Nat. Commun. 12, 879 (2021).
Athman, R. et al. Shigella flexneri infection is dependent on villin in the mouse intestine and in primary cultures of intestinal epithelial cells. Cell. Microbiol. 7, 1109–1116 (2005).