Milk and bugs educate infant immune systems

Immune-system maturation starts early in life, but studies investigating immune-system education human infants remain scarce. In a recent issue of Cell, Henrick et al. study gut microbiota and development two infant cohorts. The authors describe that Bifidobacteria can use milk sugars to produce immunoregulatory compounds induce immune tolerance reduce intestinal inflammation. Main textThe early-life is thought shape the system, potentially leading long-lasting effects on an individual’s susceptibility infections immune-mediated diseases, like allergies diabetes (Al Nabhani Eberl, 2020Al Z. Eberl G. Imprinting system by life.Mucosal Immunol. 2020; 13: 183-189Crossref PubMed Scopus (86) Google Scholar; Vatanen al., 2016Vatanen T. Kostic A.D. d’Hennezel E. Siljander H. Franzosa E.A. Yassour M. Kolde R. Vlamakis Arthur T.D. Hämäläinen A.-M. al.DIABIMMUNE Study GroupVariation microbiome LPS immunogenicity contributes autoimmunity humans.Cell. 2016; 165: 842-853Abstract Full Text PDF (625) Scholar). However, date, most life have relied animal models Scholar), while data from remains 2021Henrick B.M. Rodriguez L. Lakshmikanth Pou C. Henckel Arzoomand A. Olin Wang J. Mikes Tan al.Bifidobacteria-mediated imprinting life.Cell. 2021; 184: 1-15Abstract (95) Scholar apply advanced technologies how microbial colonizers affect maturation. cohorts Sweden United States, observe colonization breast-milk-consuming was associated with more phenotype, whereas limited Bifidobacterial activation inflammation (Figure 1).The first during months cohort 208 newborns Sweden. Extensive immune-cell plasma-protein profiling 858 longitudinally collected blood samples show transient innate soon after birth, followed production cytokines expansion cells linked adaptive responses. These changes were paralleled weeks birth. Shotgun metagenomic sequencing 347 fecal 157 highly variable at birth converged increasing age abundances members Bacteroidaceae Bifidobacteriaceae families increased over time—two findings are concordance previous communities (Bäckhed 2015Bäckhed F. Roswall Peng Y. Feng Q. Jia Kovatcheva-Datchary P. Li Xia Xie Zhong al.Dynamics stabilization year life.Cell Host Microbe. 2015; 17: 690-703Abstract (1473) 2016Yassour Härkönen Ryhänen S.J. Huttenhower Gevers D. al.Natural history impact antibiotic treatments strain-level diversity stability.Sci. Transl. Med. 8: 1173-1178Crossref (512) Previously, reported immunomodulatory functions reduced enteric preterm breastfed-term (Nguyen 2021Nguyen Holdbrooks Mishra Abrantes M.A. Eskew S. Garma Oca C.-G. McGuckin Hein C.B. Mitchell R.D. al.Impact probiotic B. infantis EVC001 feeding premature microbiome, nosocomially acquired resistance, inflammation.Front Pediatr. 9: 618009Crossref (15) Wu 2016Wu B.-B. Yang Xu X. W.-P. Effects Bifidobacterium supplementation composition response healthy infants.World 12: 177-182Crossref (40) current study, varied between focus studying effect differences developing system. Consistent earlier findings, low abundance responses characterized expanded populations concentrations pro-inflammatory (including tumor necrosis factor ?, interleukin [IL]-1?, IL-13, IL-17A) plasma samples. contrast, high anti-inflammatory, phenotype by, among other factors, regulatory T elevated IL-10 IL-27.Most breastfed beyond 3 age. When drinking their mother’s milk, receive oligosaccharides (HMOs), prebiotic properties bacteria as nutrient source. HMOs, which one major components breast thus likely community and, concomitantly, infancy. Indeed, capacity metabolize HMOs correlated immune-related proteins, specifically lower levels higher cytokine IL-27.To further investigate utilize regulation, performed intervention 60 American infants. All exclusively randomized either no (n = 31) or longum subspecies (B. infantis) 29), strain carrying complete set genes for metabolizing HMOs. Supplementation given 7 24 days postpartum. For 20 each group, shotgun available 6 days, before started, stopped. combined analysis, observed pathogenic Clostridiaceae, Enterobacteriaceae, Staphylococcaceae positively drive helper 2 (Th2) Th17 responses, negatively these cytokines. Accordingly, Th2 group compared control without intervention. To elucidate vitro cell polarization assays using waters supplement targeted transcriptomics proteomics profiling. Here, they naive Th0 polarized presence water showed decreased expression Th17-associated IL23R gene Th1-associated controls. also used explore molecules Th polarization, tryptophan derivative indole-3-lactic acid identified playing key role. Indole-3-lactic bacterial metabolite produced large quantities when substrate (Ehrlich 2020Ehrlich A.M. Pacheco A.R. Taft Huda M.N. Mishchuk Goodson M.L. Slupsky Barile al.Indole-3-lactic Bifidobacterium-dominated significantly decreases epithelial cells.BMC Microbiol. 20: 357Crossref (43) upregulated galectin-1, known inducer (Sundblad 2018Sundblad V. Quintar A.A. Morosi L.G. Niveloni S.I. Cabanne Smecuol Mauriño Mariño K.V. Bai J.C. Maldonado C.A. Rabinovich G.A. Galectins inflammation: Galectin-1 delineates treatment celiac disease patients.Front. 2018; 379Crossref (23) thereby mediating regulation EVC001-supplemented sum, both combination HMO-metabolizing modulate infancy.Henrick provide unique insights into interaction Their extensive analysis communities, cells, proteins several hundred than 200 exceptional, especially considering difficulties obtaining sufficient sample material different analyses life. addition thorough characterization parallel extend cell-culture immune-modulating life.As any good raises research questions. One yet-unexplored question what HMO profile depends genetics, genetic variance FUT2 FUT3 determining specific (Lefebvre 2020Lefebvre Shevlyakova Charpagne Marquis Vogel Kirsten Kiess W. Austin Sprenger N. Binia Time lactation maternal fucosyltransferase polymorphisms determine variability oligosaccharides.Front. Nutr. 7: 574459Crossref (26) Studying genetics interplay utilized thrive immune-modulatory should help our understanding factors aid gut-microbiome Additionally, role formula, rarely contains system.Another important whether will desired health outcomes, i.e., metabolizers colonizing following incidences diseases type 1 diabetes. So far, do not few years Longer follow-up this be necessary answer question. Additional (clinical) trials therapeutic potential young infants, well individuals suffering might develop new prevention strategies many immune-system-associated conditions. 1). IL-27. Most As Another We thank Katherine McIntyre critically revising manuscript. A.Z. supported European Research Council (ERC starting grant 715772 ) Dutch (NWO-VIDI 016.178.056 ).