Dietary cellulose induces anti-inflammatory immunity and transcriptional programs via maturation of the intestinal microbiota

Gut Microbes. 2020 Nov 9;12(1):1-17. doi: 10.1080/19490976.2020.1829962.

Abstract

Although it is generally accepted that dietary fiber is health promoting, the underlying immunological and molecular mechanisms are not well defined, especially with respect to cellulose, the most ubiquitous dietary fiber. Here, the impact of dietary cellulose on intestinal microbiota, immune responses and gene expression in health and disease was examined. Lack of dietary cellulose disrupted the age-related diversification of the intestinal microbiota, which subsequently remained in an immature state. Interestingly, one of the most affected microbial genera was Alistipes which is equipped with enzymes to degrade cellulose. Absence of cellulose changed the microbial metabolome, skewed intestinal immune responses toward inflammation, altered the gene expression of intestinal epithelial cells and mice showed increased sensitivity to colitis induction. In contrast, mice with a defined microbiota including A. finegoldii showed enhanced colonic expression of intestinal IL-22 and Reg3γ restoring intestinal barrier function. This study supports the epidemiological observations and adds a causal explanation for the health promoting effects of the most common biopolymer on earth.

Keywords: Alistipes; Cellulose; IL-22; Reg3γ; bile acids; inflammation; insoluble fiber; microbial diversity; microbiota maturation; mucosal homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Bacteroidetes / metabolism
  • Cellulose / metabolism*
  • Colitis / pathology
  • Dietary Fiber / metabolism*
  • Epithelial Cells / metabolism*
  • Gastrointestinal Microbiome / physiology*
  • Inflammation / pathology
  • Interleukin-22
  • Interleukins / biosynthesis
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pancreatitis-Associated Proteins / biosynthesis

Substances

  • Anti-Inflammatory Agents
  • Dietary Fiber
  • Interleukins
  • Pancreatitis-Associated Proteins
  • Reg3g protein, mouse
  • Cellulose

Supplementary concepts

  • Alistipes finegoldii

Grants and funding

This work was supported by the Jürgen Manchot Stiftung and the von Behring Röntgen Stiftung under Grant 66-0008 and 66-0020. DFG Priority Programm SPP1656 under Grant STE 776/3-1 and BL 953/5-2. The work was also supported by the LOEWE Center DRUID (Projects C4 to US) within the Hessian Excellence Program.