2. Academic Validation
  3. Bifidobacteria-mediated immune system imprinting early in life

Bifidobacteria-mediated immune system imprinting early in life

  • Cell. 2021 Jul 22;184(15):3884-3898.e11. doi: 10.1016/j.cell.2021.05.030.
Bethany M Henrick 1,  Lucie Rodriguez 2,  Tadepally Lakshmikanth 2,  Christian Pou 2,  Ewa Henckel 3,  Aron Arzoomand 2,  Axel Olin 2,  Jun Wang 2,  Jaromir Mikes 2,  Ziyang Tan 2,  Yang Chen 2,  Amy M Ehrlich 4,  Anna Karin Bernhardsson 2,  Constantin Habimana Mugabo 2,  Ylva Ambrosiani 5,  Anna Gustafsson 6,  Stephanie Chew 4,  Heather K Brown 4,  Johann Prambs 4,  Kajsa Bohlin 6,  Ryan D Mitchell 4,  Mark A Underwood 7,  Jennifer T Smilowitz 8,  J Bruce German 8,  Steven A Frese 9,  Petter Brodin 10
Affiliations

Affiliations

  • 1 Evolve BioSystems, Inc., Davis, CA 95618, USA; Department of Food Science and Technology, University of Nebraska, Lincoln, Lincoln, NE 68588-6205, USA. Electronic address: [email protected].
  • 2 Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, 17121 Solna, Sweden.
  • 3 Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, 17121 Solna, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 14152 Stockholm, Sweden; Department of Neonatology, Karolinska University Hospital, 14186 Stockholm, Sweden.
  • 4 Evolve BioSystems, Inc., Davis, CA 95618, USA.
  • 5 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 14152 Stockholm, Sweden.
  • 6 Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 14152 Stockholm, Sweden; Department of Neonatology, Karolinska University Hospital, 14186 Stockholm, Sweden.
  • 7 Foods for Health Institute, University of California, Davis, Davis, CA 95616, USA; Department of Pediatrics, University of California Davis Children's Hospital, Sacramento, CA 95817, USA.
  • 8 Foods for Health Institute, University of California, Davis, Davis, CA 95616, USA; Department of Food Science and Technology, University of California, Davis, Davis, CA 95616, USA.
  • 9 Department of Food Science and Technology, University of Nebraska, Lincoln, Lincoln, NE 68588-6205, USA; Department of Nutrition, University of Nevada, Reno, Reno, NV 89557, USA.
  • 10 Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, 17121 Solna, Sweden; Pediatric Rheumatology, Karolinska University Hospital, 17176 Solna, Sweden. Electronic address: [email protected].
PMID: 34143954 DOI: 10.1016/j.cell.2021.05.030
Abstract

Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host's immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon β (IFNβ) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory Galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.

Keywords

human immunology; immune system development; mass cytometry; metagenomics; microbiome; neonate; neonatology; newborn immune systems; systems immunology; transcriptome.

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