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A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility
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SUMMARY Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
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“In one such study using a gnotobiotic mouse model, in which there was colonization with harvested human gut microbiota, chronic dietary fibre deficiency resulted in the gut microbiota using host-secreted mucus glycoproteins as an alternate nutrient source [54].”
From The Health Benefits of Dietary Fibre (2020) · cites this paper as [54]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Akkermansia is a mucin-degrading bacterium and investigations on mice have found that Akkermansia can deplete the intestinal mucosal layer, decrease the number of goblet cells, produce drier stools, slow colonic transit, and impair intestinal barrier function [106–108].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [106]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“There was subsequent erosion of the colonic mucus barrier with greater epithelial access and predisposition to lethal colitis [54].”
From The Health Benefits of Dietary Fibre (2020) · cites this paper as [54]
The cited source says what the claim attributes to it.
In the citing paper
“In addition to weight loss, the MD has been reported to have a well-established anti-inflammatory activity, which is mainly due to the microbiota-derived production of short chain fatty acids that are induced by dietary fibre [14] and the high intake of both polyunsaturated fatty acids (PUFA) omega 3 and antioxidants contained in fruits, vegetables, extra-virgin olive oil, and wine [15,16,17].”
From Adherence to the Mediterranean Diet, Dietary Patterns and Body Composition in Women with Polycystic Ovary Syndrome (PCOS) (2019) · cites this paper as [14]
In the citing paper
“Akkermansia has been positively associated with metabolic health (Derrien et al., 2017), but has also been associated with low-fiber diets and is rare in populations consuming traditional diets (Earle et al., 2015; Desai et al., 2016; Smits et al., 2017).”
From Gut-microbiota-targeted diets modulate human immune status (2021) · cites this paper as Desai et al., 2016
In the citing paper
“a chronic or intermittent low-fiber diet in gnotobiotic mice stimulates the proliferation and activity of mucin-degrading bacteria, resulting in mucus layer erosion and increased pathogen susceptibility”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [640]
In the citing paper
“The role of diet27 in microbial alterations is of significant interest in FGIDs as dietary intolerances are commonly reported in FGIDs and patients may alter or restrict their diets based on perceived associations between symptoms and food28, 29.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [27]
In the citing paper
“Hence microbial starvation such as with decreased consumption of fiber can increase microbial reliance on the mucus polysaccharides resulting in degradation of the mucus layer and increasing susceptibility to opportunistic pathogens and inflammation27, 86.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [27]
In the citing paper
“Not surprisingly, ECOG performance status ≥ 1 was another independent prognostic factor for this cohort 31 .”
From Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer (2022) · cites this paper as [31]
In the citing paper
“Given that many of the response-associated bacteria identified in our cohort have known roles in starch degradation and fiber fermentation (25–29)”
From Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response (2021) · cites this paper as [29]
In the citing paper
“Nevertheless, an increase in Akkermansia has also been linked to reduced mucus and decreased resistance to a specific pathogen in mice [55].”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity via AMPK/SOD2 Pathway (2023) · cites this paper as [55]
In the citing paper
“The Gram-negative bacteria, Akkermansia, can degrade mucin, cause intestinal inflammation and permeability, and increase endotoxemia and systemic inflammation, eventually promoting neuropathology [53,54,55].”
From Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease (2023) · cites this paper as [54]
In the citing paper
“Over-grazing of the mucus layer by these species may be an important consequence of MAC restriction, as chronic foraging has been shown to compromise barrier integrity and enhance inflammation and pathogen susceptibility in animal studies (12, 13).”
From The gut microbiota at the intersection of diet and human health (2018) · cites this paper as [13]
In the citing paper
“These include proteases in B. thetaiotaomicron (BT4244) or Bacteroides caccae.126,127”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [127]
In the citing paper
“Different mucin-degrading proteases have been also described in Bacteroides, a common commensal of the human intestine.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [127]
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Metadata
- Authors
- Desai, M. S., Seekatz, A. M., Koropatkin, N. M., Kamada, N., Hickey, C. A., Wolter, M., Pudlo, N. A., Kitamoto, S., Terrapon, N., Muller, A., Young, V. B., Henrissat, B., Wilmes, P., Stappenbeck, T. S., Núñez, G., & Martens, E. C.
- Affiliations
- University of Michigan (US)
- Washington University in St. Louis (US)
- Luxembourg Institute of Health (LU)
- Aix-Marseille Université (FR)
- Luxembourg Centre for Systems Biomedicine (LU)
- Corresponding author
- Desai, Mahesh S.
- Martens, Eric C.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 167
- Issue
- 5
- Pages
- 1339-1353.e21
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5131798
- OpenAlex
- W2552041992
- Semantic Scholar
- 5b4bb84bcf8463025f0e1a4237657b4407328ebd
- Cited by
- 2,805
- References
- 50
- Citations by year
- 2026: 270 · 2025: 308 · 2024: 357 · 2023: 326 · 2022: 386 · 2021: 371 · 2020: 273 · 2019: 241 · 2018: 162 · 2017: 103 · 2016: 4
- FWCI
- 88.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, other-oa)
- HAL AMU (submittedVersion, other-oa)
- Funders
- Luxembourg National Research Fund (FNR) INTER Mobility (13/5624108)
- CORE (C15/BM/10318186, 11/1186762)
- Luxembourg Ministry of Higher Education and Research
- FNR ATTRACT (A09/03)
- European Union Joint Programming in Neurodegenerative Diseases (INTER/JPND/12/01)
- NIH R01 (GM099513)
- University of Michigan Host Microbiome Initiative and Center for Gastrointestinal Research (DK034933)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- gut microbiota, colonic mucus barrier, mucus glycoproteins, intestinal barrier dysfunction, Citrobacter rodentium, colitis, pathogen susceptibility, gnotobiotic mouse model, host-microbe interactions
- MeSH terms
- Gastrointestinal Microbiome, Animals, Colitis, Colon, Dietary Fiber, Disease Susceptibility, Enterobacteriaceae Infections, Escherichia coli, Female, Germ-Free Life, Humans, Intestinal Mucosa, Male, Citrobacter rodentium, Mice, Mucin-2
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