title: Eggshell membrane powder ameliorates intestinal inflammation by facilitating the restitution of epithelial injury and alleviating microbial dysbiosis.
abstract: Gut microbiota is an essential factor in the shaping of intestinal immune system development and driving inflammation in inflammatory bowel disease (IBD). We report the effects and microbe-host interactions underlying an intervention using fine powder of eggshell membrane (ESM) against IBD. ESM attenuated lipopolysaccharide-induced inflammatory cytokine production and promoted the Caco-2 cell proliferation by up-regulating growth factors in vitro. In a murine model of dextran sodium sulphate-induced colitis, ESM significantly suppressed the disease activity index and colon shortening. These effects were associated with significant ameliorations of gene expressions of inflammatory mediators, intestinal epithelial cell proliferation, restitution-related factors and antimicrobial peptides. Multifaceted integrated omics analyses revealed improved levels of energy metabolism-related genes, proteins and metabolites. Concomitantly, cecal metagenomic information established an essential role of ESM in improving dysbiosis characterized by increasing the diversity of bacteria and decreasing absolute numbers of pathogenic bacteria such as Enterobacteriaceae and E. coli, as well as in the regulation of the expansion of Th17 cells by suppressing the overgrowth of segmented filamentous bacteria. Such modulations have functional effects on the host; i.e., repairing the epithelium, regulating energy requirements and eventually alleviating mucosal inflammation. These findings are first insights into ESM's modulation of microbiota and IBD suppression, providing new perspectives on the prevention/treatment of IBD.
authors.affiliation: Corporate Sponsored Research Program "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Manaka
authors.initials: M
authors.lastname: Hanate
authors.affiliation: Corporate Sponsored Research Program "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan.|Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
authors.forename: Wanping
authors.initials: W
authors.lastname: Aw
authors.affiliation: Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Hokkaido, Sapporo, Japan.
authors.forename: Hideomi
authors.initials: H
authors.lastname: Itoh
authors.affiliation: Corporate Sponsored Research Program "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.affiliation: Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kobayashi
authors.affiliation: Research Center for Food Safety and Department of Applied Biological Chemistry, Graduate School of Agricultural and Life sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hachimura
authors.affiliation: Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Institute for Advanced Biosciences, Keio University, Yamagata, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.affiliation: ALMADO Inc., Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hasebe
authors.affiliation: Corporate Sponsored Research Program "Food for Life," Organization for Interdisciplinary Research Projects, The University of Tokyo, Tokyo, Japan.|Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kato
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control / Q000662:veterinary; D016264:Dextran Sulfate / Q000633:toxicity; D064806:Dysbiosis; D004528:Egg Shell / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome / Q000187:drug effects
chemical_list: D023181:Antimicrobial Cationic Peptides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016264:Dextran Sulfate