Related Experiment Video

Updated: Jul 6, 2026

Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins
09:24

Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins

Published on: June 14, 2016

Mucin degradation by Akkermansia muciniphila promotes Alistipes-dependent tryptophan metabolism and Th17-driven

Xun Lin1, Ankita Singh1, Xindi Shan2

  • 1Department of Microbiology and Immunology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, United States.

Mucosal Immunology
|July 4, 2026
PubMed

Insights

Akkermansia muciniphila exacerbates multiple sclerosis (MS) by promoting gut bacteria that increase neuroinflammation via tryptophan metabolism. Restricting dietary tryptophan may reduce MS severity.

Area of Science:

  • Neuroimmunology
  • Microbiome Research
  • Gastroenterology

Background:

  • Multiple sclerosis (MS) involves gut microbiota alterations.
  • The specific role of Akkermansia muciniphila (A. muciniphila) in MS pathogenesis is not fully understood.
  • Gut barrier dysfunction is implicated in MS.

Purpose of the Study:

  • To investigate the role of A. muciniphila in MS.
  • To elucidate the mechanisms linking gut microbiota to neuroinflammation in MS.
  • To explore therapeutic potential of dietary interventions.

Main Methods:

  • Analysis of serum markers (LPS, anti-LPS IgG, anti-A. muciniphila IgA) in relapsing-remitting MS (RRMS) patients.
  • Assessment of A. muciniphila-induced T cell responses (Th17) in peripheral blood mononuclear cells (PBMCs).
  • Utilized experimental autoimmune encephalomyelitis (EAE) mouse model to study A. muciniphila colonization effects on disease severity and immune cell infiltration in the spinal cord.
  • Investigated microbial metabolism pathways (tryptophan, mucin degradation) and aryl hydrocarbon receptor (AhR) agonist production.
  • Evaluated the impact of dietary tryptophan restriction on EAE severity.

Main Results:

  • RRMS patients showed elevated serum LPS and anti-LPS IgG, indicating gut barrier impairment.
  • Increased serum anti-A. muciniphila IgA and heightened A. muciniphila-stimulated Th17 responses were observed in RRMS patients.
  • A. muciniphila colonization worsened EAE severity, increasing pro-inflammatory CD4+ T cell infiltration (GM-CSF+, IL-17A+) in the spinal cord.
  • A. muciniphila promoted tryptophan metabolism and AhR agonist production during EAE by supporting the growth of Alistipes onderdonkii (A. onderdonkii) via mucin degradation.
  • Dietary tryptophan restriction significantly reduced EAE severity.

Conclusions:

  • A. muciniphila exacerbates MS by fostering a gut environment that enhances neuroinflammation.
  • A cross-feeding interaction between A. muciniphila and A. onderdonkii drives microbial tryptophan metabolism, leading to increased AhR agonist production and Th17-mediated neuroinflammation.
  • Targeting microbial metabolism, specifically tryptophan pathways, presents a potential therapeutic strategy for MS.
Keywords:
Akkermansia muciniphilaEAETh17 cells

Related Concept Videos

Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
Dysbiosis of the Gut Microbiota01:18

Dysbiosis of the Gut Microbiota

The human gut microbiome includes a diverse array of microbial species, including beneficial commensals and opportunistic pathogens, which interact to support host health. These microbes contribute to essential functions such as nutrient metabolism, immune system modulation, and maintenance of intestinal barrier integrity. However, disruptions to this equilibrium—referred to as dysbiosis—can have widespread physiological consequences.Dysbiosis is often characterized by reduced microbial...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
Gastritis II: Pathophysiology01:26

Gastritis II: Pathophysiology

The pathophysiology of gastritis begins with the colonization of the stomach lining by Helicobacter pylori (H. pylori). This bacterium spreads mainly via the oral-oral route through saliva or shared utensils, and can also be transmitted in overcrowded or unhygienic environments through contaminated water, despite its brief survival outside the body.ColonizationOnce ingested, H. pylori enters the stomach and begins colonization by navigating through the mucus layer lining the stomach wall. It...
Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors01:24

Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors

Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI)  tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining. Bicarbonate,...
Microbiota of the Respiratory Tract01:29

Microbiota of the Respiratory Tract

The human respiratory tract, comprising the upper and lower segments, serves as a critical interface with the external environment. The upper respiratory tract (URT)—including the nostrils, sinuses, pharynx, and oropharynx—is heavily colonized by microbes, while the lower respiratory tract (LRT), composed of the larynx, trachea, bronchi, and lungs, was long thought to be sterile. However, recent molecular studies have revealed that the lungs are not devoid of microbes but act more like...