CoChat
Sign Up
Cited by 700Gut microbiota and healthGastrointestinal motility and disordersAnimal Nutrition and Physiology

The composition of the gut microbiota shapes the colon mucus barrier

Open access
Jakobsson, Hedvig E, Rodríguez‐Piñeiro, Ana M, Schütte, André, Ermund, Anna, Boysen, Preben, Bemark, Mats, Sommer, Felix, Bäckhed, Fredrik +2 more·2015·The EMBO Reports
DOI 10.15252/embr.201439263PMC PMC4328744
Open this paper in CoChat — free accountOpen PDF

Abstract

Two C57BL/6 mice colonies maintained in two rooms of the same specific pathogen-free (SPF) facility were found to have different gut microbiota and a mucus phenotype that was specific for each colony. The thickness and growth of the colon mucus were similar in the two colonies. However, one colony had mucus that was impenetrable to bacteria or beads the size of bacteria-which is comparable to what we observed in free-living wild mice-whereas the other colony had an inner mucus layer penetrable to bacteria and beads. The different properties of the mucus depended on the microbiota, as they were transmissible by transfer of caecal microbiota to germ-free mice. Mice with an impenetrable mucus layer had increased amounts of Erysipelotrichi, whereas mice with a penetrable mucus layer had higher levels of Proteobacteria and TM7 bacteria in the distal colon mucus. Thus, our study shows that bacteria and their community structure affect mucus barrier properties in ways that can have implications for health and disease. It also highlights that genetically identical animals housed in the same facility can have rather distinct microbiotas and barrier structures.

Integrity signals

Registry

Crossref · 10.15252/embr.201439263

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 46 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Two C57BL/6 mouse colonies kept in separate rooms of the same SPF facility had different gut microbiota.

    “Two C57BL/6 mice colonies maintained in two rooms of the same specific pathogen-free (SPF) facility were found to have different gut microbiota and a mucus phenotype that was specific for each colony.”
    • Also stated in: § Bacterial composition in the two husbandries · boosted
      “The microbiota throughout the gut thus clearly differed between the two colonies housed in adjacent rooms in the same animal facility.”
    Quote in the paperSubstantial claim
  • Findingown data

    The other colony had an inner mucus layer penetrable to bacteria and beads.

    “However, one colony had mucus that was impenetrable to bacteria or beads the size of bacteria—which is comparable to what we observed in free-living wild mice—whereas the other colony had an inner mucus layer penetrable to bacteria and beads.”
    Quote in the paperSubstantial claim
  • Findingown data

    One colony had mucus impenetrable to bacteria or bacteria-sized beads, comparable to free-living wild mice.

    “However, one colony had mucus that was impenetrable to bacteria or beads the size of bacteria—which is comparable to what we observed in free-living wild mice—whereas the other colony had an inner mucus layer penetrable to bacteria and beads.”
    Quote in the paperSubstantial claim
  • Findingown data

    Mice with penetrable mucus had higher Proteobacteria and TM7 in distal colon mucus.

    “Mice with an impenetrable mucus layer had increased amounts of Erysipelotrichi, whereas mice with a penetrable mucus layer had higher levels of Proteobacteria and TM7 bacteria in the distal colon mucus.”
    Quote in the paperSubstantial claim
  • Findingown data

    Mice with impenetrable mucus had increased Erysipelotrichi.

    “Mice with an impenetrable mucus layer had increased amounts of Erysipelotrichi, whereas mice with a penetrable mucus layer had higher levels of Proteobacteria and TM7 bacteria in the distal colon mucus.”
    Quote in the paperSubstantial claim
  • May combine two claims. 43
  • Classified as probably not a substantial claim. 22
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Colon mucus thickness and growth were similar between the two colonies.

    “The thickness and growth of the colon mucus were similar in the two colonies.”
    • Also stated in: § Differences in the mucus quality in mice from the two husbandries · plain
      “The thickness of the inner mucus layer as well as the mucus growth did not differ significantly between the two rooms on either food (Fig3B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Immunohistochemistry showed bacteria separated from the epithelium by a well-stratified mucus layer in Room 1 colonized mice, but bacteria close to the epithelium in Room 2 colonized mice.

    “Immunohistochemistry revealed that the bacteria were separated from the epithelium by a well-stratified mucus layer in Room 1, but bacteria were in close proximity to the epithelium of mice colonized with microbiota from Room 2 (Fig5D).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    On Food A, Room 1 mice were significantly heavier than Room 2 mice (P = 0.022).

    “On Food A, the mice bred in Room 1 were significantly heavier compared to mice bred in Room 2 (P = 0.022, Supplementary Fig S1A).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Small intestinal mucus thickness before and after aspiration did not differ between rooms or diets.

    “The small intestinal mucus is normally easily removed by aspiration, and the thickness was measured before (pre) and after (post) aspiration. No differences were observed between the rooms or diets (Fig3A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The major difference between lumen- and mucus-associated microbiota was in distal colon, where Deferribacteres had higher abundance in both rooms.

    “The major difference between the lumen- and mucus-associated microbiota was found in the distal colon where the phyla Deferribacteres had higher abundance in both rooms (Supplementary Fig S4, Table1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    FISH showed bacteria penetrated the inner mucus layer at distinct locations in Room 2; separation was observed in other areas, and most bacteria were not in direct contact with the epithelial surface.

    “When bacteria were localized in relation to the colon mucus using fluorescent in situ hybridization, bacteria penetrated the inner mucus layer at distinct locations. A separation between epithelium and bacteria was observed in other areas and most bacteria were still not in direct contact with the epithelial surface.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Betaproteobacteria and Epsilonproteobacteria were higher in mucus of Room 2 mice, and Epsilonproteobacteria were significantly more abundant in distal colon lumen and caecum.

    “Within this phylum, the classes Betaproteobacteria and Epsilonproteobacteria were found at higher levels in the mucus of mice in Room 2 and Epsilonproteobacteria were significantly more abundant in distal colon lumen and caecum (Fig1D, Table1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Allobaculum, the dominant genus in Erysipelotrichi, was higher at all locations in Room 1 and significantly so in lumen samples.

    “The dominant genus within this class contributing to this difference was the genus Allobaculum, which was also found in higher relative abundances at all locations and significantly so in the lumen samples (Fig2B, Table1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Altering diet from weaning to Food B caused some shift in microbiota, but less than the difference between rooms.

    “Altering the diet from weaning gave some shift in the microbiota, but less than the difference between the two rooms.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    There was a tendency towards longer crypts in Room 2, but it did not reach significance.

    “A tendency towards longer crypts in mice from Room 2 was also observed, but this did not reach significance (Fig4D).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    After fixation, the inner mucus layer was thinner and stratification was not evident in sections from animals fed Food B in both rooms, but the difference between rooms remained.

    “The inner mucus layer was after fixation observed to be thinner, and stratification was not evident in sections from animals fed Food B in both rooms, but the difference between the two rooms remained (Fig4B).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Stool from mice fed Food A was hard and formed distinct pellets, while stool from mice fed Food B was looser and did not form hard pellets.

    “The stool of mice fed Food A was hard and formed distinct pellets, while the stool in animals fed Food B had a looser consistency and did not form hard pellets.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Bacterial diversity was lowest in ileum and highest in distal colon.

    “When bacterial diversity was studied (Supplementary Figs S2 and S3), the ileum showed the lowest diversity and the distal colon the highest.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Ki67-positive dividing cells were significantly increased in distal colon of Room 2 compared with Room 1.

    “The labelled cells were significantly increased in mice from Room 2 as compared to Room 1 (Fig4F and H).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Principal Coordinates Unweighted UniFrac analysis separated ileum and colon samples along the first component and the two rooms along PC2 on Food A.

    “Principal Coordinates Unweighted UniFrac analysis 20 showed separation of ileum and colon samples along the first component, whereas the two rooms clearly separated along PC2 on Food A (Fig1A and B).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Lozupone C, Knight R (2005) UniFrac: a new phylogenetic method for comparing microbial communities. Appl Environ Microbiol 71: 8228–8235 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Inflammatory markers S100a8, S100a9, and eosinophil cationic protein 3 were not detected, and no difference in albumin or alpha 2-macroglobulin was found.

    “Inflammatory markers as S100a8, S100a9 and eosinophil cationic protein 3 were not detected and no difference in albumin or alpha 2-macroglobulin was found between the groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Room 1 mice secreted mucus impenetrable to beads, whereas Room 2 mice had more penetrable mucus.

    “As shown before, mice from Room 1 secreted mucus that was impenetrable to the beads, whereas the mucus on explants from mice housed in Room 2 was more penetrable (Fig3C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Germ-free mice colonized with Room 2 microbiota had a more penetrable inner mucus layer, while those colonized with Room 1 microbiota had mucus impervious to beads.

    “Mucus penetrability phenotypes were again different as a more penetrable inner mucus layer was observed in mice colonized with microbiota from Room 2, while mice colonized with microbiota from Room 1 showed a mucus layer impervious to beads (Fig5B and C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    All mice on Food B had higher relative abundances of Proteobacteria at all gut locations and in both rooms, with significant differences in ileum lumen, ileum mucus and caecum in Room 1, and in distal colon lumen in both rooms.

    “All mice on Food B showed higher relative abundances of the phylum Proteobacteria at all locations along the gut and in both rooms with significant differences in ileum lumen, ileum mucus and caecum in Room 1, and in distal colon lumen in both rooms (Supplementary Fig S5, Supplementary Table S1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Food B increased mucus penetrability in both groups, but a difference remained between Room 1 and Room 2 mice.

    “Mice given food B showed increased penetrability in both groups, but a difference still remained between Room 1 and 2 mice (Fig3C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Proteomic analyses showed no major differences between rooms and a high correlation of proteins identified.

    “To analyse the reasons for the different mucus properties, proteomic analyses were performed showing no major differences between the rooms and a high correlation of the proteins identified in the two rooms (Supplementary Fig S6D and E).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In ileum mucus, Candidatus arthromitus (SFB) was higher in Room 2; SFB was also higher in distal colon in Room 2.

    “In ileum mucus, the dominant genus within the Clostridia class was Candidatus arthromitus (segmented filamentous bacteria, SFB), which was also found in higher levels in Room 2 (Table1). SFB also showed a small but significant difference between the rooms in the distal colon with higher levels in Room 2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Colon inner mucus layer thickness and mucus growth did not differ significantly between rooms on either food.

    “The thickness of the inner mucus layer as well as the mucus growth did not differ significantly between the two rooms on either food (Fig3B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The number of infiltrating immune cells in lamina propria was higher in Room 2 but did not reach significance.

    “The number of these cells was higher in the Room 2 animals; however, it did not reach significance (Fig4G and Supplementary Fig S7A), but there was no major difference in the overall histology between the groups (Supplementary Fig S7B and C).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Our study corroborates previous studies showing an association between altered diets and an increase in Erysipelotrichi and Allobaculum.

    “Our study corroborates previous studies showing an association between altered diets and an increase in Erysipelotrichi and Allobaculum, but various effects are shown for fat-enriched diets 29, 30, 31, 32.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [29] Everard A, Lazarevic V, Gaia N, Johansson M, Stahlman M, Backhed F, Delzenne NM, Schrenzel J, Francois P, Cani PD (2014) Microbiome of prebiotic‐treated mice reveals novel targets involved in host response during obesity. ISME J 8: 2116–2130 source

      Not checked in the free run.

    • cites [30] Islam KB, Fukiya S, Hagio M, Fujii N, Ishizuka S, Ooka T, Ogura Y, Hayashi T, Yokota A (2011) Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141: 1773–1781 source

      Not checked in the free run.

    • cites [31] Martinez I, Wallace G, Zhang C, Legge R, Benson AK, Carr TP, Moriyama EN, Walter J (2009) Diet‐induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota. Appl Environ Microbiol 75: 4175–4184 source

      Not checked in the free run.

    • cites [32] Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI (2009) The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med 1: 6ra14 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    We have also observed different inner mucus phenotypes in animals from different vendors.

    “We have also observed different inner mucus phenotypes in animals from different vendors, further emphasizing the need for standardization and caution.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The present study reveals subtle differences in the microbiota between the two mouse colonies.

    “Even though the present study reveals subtle differences in the microbiota between the two mouse colonies, an increased inflammatory tone was observed in Room 2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Muc2-deficient mice lack a protective inner mucus layer, have direct bacteria-epithelium contact, and develop severe colitis.

    “Muc2-deficient mice totally lack a protective inner mucus layer and have direct contact of bacteria with the epithelium and these mice develop severe colitis 14.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Johansson ME, Phillipson M, Petersson J, Velcich A, Holm L, Hansson GC (2008) The inner of the two Muc2 mucin‐dependent mucus layers in colon is devoid of bacteria. Proc Natl Acad Sci USA 105: 15064–15069 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The different mucus properties depended on the microbiota and were transmissible by caecal microbiota transfer to germ-free mice.

    “The different properties of the mucus depended on the microbiota, as they were transmissible by transfer of caecal microbiota to germ-free mice.”
    • Also stated in: § The two different mucus phenotypes were reproduced by colonization of germ-free mice · plain
      “The composition of intestinal microbiota thus has a major influence on the properties of the inner colon mucus barrier.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Colonization of germ-free mice with caecal microbiota from a room reproduces that room's relevant microbiota composition.
    • Rests on an assumption: Housing colonized germ-free mice in the corresponding room does not introduce room-specific effects that confound the mucus phenotype.

  • May combine two claims.

    Interpretationown data

    Bacteria and their community structure affect mucus barrier properties, with implications for health and disease.

    “Thus, our study shows that bacteria and their community structure affect mucus barrier properties in ways that can have implications for health and disease.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mucus is structurally built around MUC2 mucin, which after secretion expands and forms stacked sheets that make the stratified mucus layer.

    “The mucus is structurally built around the MUC2 mucin that after secretion from the goblet cell expands dramatically and forms sheets of MUC2 networks that stack and form the stratified mucus layer 16.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Ambort D, Johansson ME, Gustafsson JK, Nilsson HE, Ermund A, Johansson BR, Koeck PJ, Hebert H, Hansson GC (2012) Calcium and pH‐dependent packing and release of the gel‐forming MUC2 mucin. Proc Natl Acad Sci USA 109: 5645–5650 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Deficiencies in O-glycan decoration cause faster Muc2 network degradation, increased bacterial contact with the cell surface, and spontaneous colitis.

    “Deficiencies in decorating the mucus with O-glycans cause a faster degradation of the Muc2 mucin network resulting in increased bacterial contact with the cell surface and development of spontaneous colitis 19.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Fu J, Wei B, Wen T, Johansson ME, Liu X, Bradford E, Thomsson KA, McGee S, Mansour L, Tong M et al (2011) Loss of intestinal core 1‐derived O‐glycans causes spontaneous colitis in mice. J Clin Invest 121: 1657–1666 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The two C57BL/6 strains bred separately had stable but different microbiota that were vertically transmitted.

    “It was thus concluded that the two C57BL/6 mice strains bred separately had stable, but different microbiota that were vertically transmitted.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The more developed mucus layer in wild mice supports the influence of microbiota on mucus and supports using Room 1 as a reasonable model.

    “Nevertheless, these mice often had an even more developed mucus layer than observed in Room 1, which further supports the influence of the microbiota on mucus and that the Room 1 can be considered as a reasonable model.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    The two colonies were maintained on different diets, but diet impact was controlled within one generation by feeding the same chow from weaning.

    “The two colonies were maintained on different diets with different composition, but we controlled for the impact of diet, at least within one generation of offspring, by feeding the mice in the two colonies the same chow (Food A, standard chow or Food B, autoclaved chow) from weaning.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Exoglycosidases are usually arranged in specialized genetic loci for utilizing specific substrates such as starch (Sus) and xylose-containing polysaccharides (PUL).

    “The exoglycosidases are usually arranged in specialized genetic loci for utilizing specific types of substrates as, for example, starch (Sus) and xylose-containing polysaccharides (PUL) 27.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] Larsbrink J, Rogers TE, Hemsworth GR, McKee LS, Tauzin AS, Spadiut O, Klinter S, Pudlo NA, Urs K, Koropatkin NM et al (2014) A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes. Nature 506: 498–502 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Free-living mice have mucus that is even better developed, thicker, and more stratified with bacteria further separated from the epithelium than Room 1.

    “Thus, free-living mice have mucus that is even better developed, thicker and more stratified with bacteria further separated from the epithelium than in Room 1.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Free-living wild mice provide a valid reference for a normal protective colon mucus phenotype.

  • May combine two claims.

    Premisecitation

    Commensal bacteria live in the non-attached and expanded outer mucus of the colon, where they can cleave off and use mucin glycans as an energy source.

    “The commensal bacteria live in the non-attached and expanded outer mucus of colon 26, where they can cleave off and utilize mucin glycans as energy source.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Johansson ME, Holmen Larsson JM, Hansson GC (2010) Microbes and Health Sackler Colloquium: the two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host‐microbial interactions. Proc Natl Acad Sci USA 108: 4659–4665 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Protein differences were small and not likely to explain the variable mucus properties.

    “The protein differences were small and not likely to explain the variable mucus properties.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Ulcerative colitis patients with active disease have bacteria in contact with the epithelium, whereas patients in remission show a more mixed picture.

    “Ulcerative colitis (UC) patients with active disease have bacteria in contact with the epithelium, whereas patients with UC in remission show a more mixed picture 15.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Johansson ME, Gustafsson JK, Holmen‐Larsson J, Jabbar KS, Xia L, Xu H, Ghishan FK, Carvalho FA, Gewirtz AT, Sjovall H et al (2014) Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis. Gut 63: 281–291 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Genetic influences on the mucus phenotypes are less likely because germ-free mice more related to Room 2 animals formed a functional mucus barrier after colonization with Room 1 flora.

    “The origin of the germ-free mice is more related to the origin of the animals in Room 2, but as they still were able to form a functional mucus barrier upon colonization with flora from animals in Room 1, genetic influences are less likely.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    TM7 and the genus Prevotella are also increased in mice deficient in the inflammasome component Nlrp6 and suggested to be associated with inflammation.

    “TM7 and the genus Prevotella are also increased in mice deficient in the inflammasome component Nlrp6 and suggested to be associated with inflammation 51.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Hu B, Elinav E, Huber S, Strowig T, Hao L, Hafemann A, Jin C, Wunderlich C, Wunderlich T, Eisenbarth SC et al (2013) Microbiota‐induced activation of epithelial IL‐6 signaling links inflammasome‐driven inflammation with transmissible cancer. Proc Natl Acad Sci USA 110: 9862–9867 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    SFB are considered to foster normal intestinal homeostasis in healthy mice, which contrasts with the less developed colon mucus observed here.

    “However, it is considered to foster a normal intestinal homeostasis in healthy mice, something that is in contrast to the here observed less developed colon mucus 52.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Schnupf P, Gaboriau‐Routhiau V, Cerf‐Bensussan N (2013) Host interactions with Segmented Filamentous Bacteria: an unusual trade‐off that drives the post‐natal maturation of the gut immune system. Semin Immunol 25: 342–351 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Certain bacteria can destroy the mucus and its protective properties, in contrast to promoting well-developed mucus.

    “Certain bacteria can, in contrast to promoting well-developed mucus, also destroy the mucus and its protective properties.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [36] Bergstrom KS, Kissoon‐Singh V, Gibson DL, Ma C, Montero M, Sham HP, Ryz N, Huang T, Velcich A, Finlay BB et al (2010) Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa. PLoS Pathog 6: e1000902 source

      Not checked in the free run.

    • cites [37] van der Post S, Subramani DB, Backstrom M, Johansson ME, Vester‐Christensen MB, Mandel U, Bennett EP, Clausen H, Dahlen G, Sroka A et al (2013) Site‐specific O‐glycosylation on the MUC2 mucin protein inhibits cleavage by the Porphyromonas gingivalis secreted cysteine protease (RgpB). J Biol Chem 288: 14636–14646 source

      Not checked in the free run.

    • cites [38] Zarepour M, Bhullar K, Montero M, Ma C, Huang T, Velcich A, Xia L, Vallance BA (2013) The mucin Muc2 limits pathogen burdens and epithelial barrier dysfunction during Salmonella enterica serovar Typhimurium colitis. Infect Immun 81: 3672–3683 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The TM7 phylum is also found in human stool samples at low levels and proposed to play a role in intestinal inflammation.

    “The TM7 phylum is also found in human stool samples at low levels 47 and proposed to play a role in intestinal inflammation 48.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [47] Segata N, Haake SK, Mannon P, Lemon KP, Waldron L, Gevers D, Huttenhower C, Izard J (2012) Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol 13: R42 source

      Not checked in the free run.

    • cites [48] Kuehbacher T, Rehman A, Lepage P, Hellmig S, Folsch UR, Schreiber S, Ott SJ (2008) Intestinal TM7 bacterial phylogenies in active inflammatory bowel disease. J Med Microbiol 57: 1569–1576 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The class Deltaproteobacteria contains sulphur-reducing bacteria (SRB) that are also found at higher frequencies in patients with IBD as compared to healthy individuals.

    “The class Deltaproteobacteria contains sulphur-reducing bacteria (SRB) that are also found at higher frequencies in patients with IBD as compared to healthy individuals 41.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] Verma R, Verma AK, Ahuja V, Paul J (2010) Real‐time analysis of mucosal flora in patients with inflammatory bowel disease in India. J Clin Microbiol 48: 4279–4282 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mouse colitis models typically show features like crypt elongation due to increased cell proliferation, infiltration of immune cells in lamina propria, thickening of muscularis propria and weight loss, all criteria used for scoring colitis.

    “Mouse colitis models typically show features like crypt elongation due to increased cell proliferation, infiltration of immune cells in lamina propria, thickening of muscularis propria and weight loss, all criteria used for scoring colitis 33, 34.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [33] Sellon RK, Tonkonogy S, Schultz M, Dieleman LA, Grenther W, Balish E, Rennick DM, Sartor RB (1998) Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin‐10‐deficient mice. Infect Immun 66: 5224–5231 source

      Not checked in the free run.

    • cites [34] Van der SM, de Koning BA, De Bruijn AC, Velcich A, Meijerink JP, Van Goudoever JB, Buller HA, Dekker J, Van Seuningen I, Renes IB et al (2006) Muc2‐deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection. Gastroenterology 131: 117–129 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The TM7 phylum has been linked to inflammatory conditions of the mouth such as periodontitis.

    “This phylum has been linked to inflammatory conditions of the mouth such as periodontitis 46.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Liu B, Faller LL, Klitgord N, Mazumdar V, Ghodsi M, Sommer DD, Gibbons TR, Treangen TJ, Chang YC, Li S et al (2012) Deep sequencing of the oral microbiome reveals signatures of periodontal disease. PLoS ONE 7: e37919 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    TM7 is a phylum with no cultivated representatives, commonly found in the oral flora at low levels.

    “This is a phylum, with no cultivated representatives, commonly found in the oral flora at low levels 44, 45.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [44] Brinig MM, Lepp PW, Ouverney CC, Armitage GC, Relman DA (2003) Prevalence of bacteria of division TM7 in human subgingival plaque and their association with disease. Appl Environ Microbiol 69: 1687–1694 source

      Not checked in the free run.

    • cites [45] Podar M, Abulencia CB, Walcher M, Hutchison D, Zengler K, Garcia JA, Holland T, Cotton D, Hauser L, Keller M (2007) Targeted access to the genomes of low‐abundance organisms in complex microbial communities. Appl Environ Microbiol 73: 3205–3214 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    For microbiota analysis, P-values were converted to false discovery rate values (Q-values) to correct for multiple testing.

    “For the microbiota analysis, significant differences were conducted using the Wilcoxon rank-sum test, and P-values were converted to false discovery rate values (Q-values) to correct for multiple testing in the R software (http://www.r-project.org/).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The TM7 phylum has also been found in mice more susceptible to colitis caused by Helicobacter hepaticus.

    “The TM7 phylum has also been found in mice more susceptible to colitis caused by Helicobacter hepaticus 49.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Yang I, Eibach D, Kops F, Brenneke B, Woltemate S, Schulze J, Bleich A, Gruber AD, Muthupalani S, Fox JG et al (2013) Intestinal microbiota composition of interleukin‐10 deficient C57BL/6J mice and susceptibility to Helicobacter hepaticus‐induced colitis. PLoS ONE 8: e70783 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The phylum Proteobacteria has been associated with human Crohn's disease.

    “The phylum Proteobacteria has been associated with human Crohn's disease 40.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Gophna U, Sommerfeld K, Gophna S, Doolittle WF, Veldhuyzen van Zanten SJ (2006) Differences between tissue‐associated intestinal microfloras of patients with Crohn's disease and ulcerative colitis. J Clin Microbiol 44: 4136–4141 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Species of lower taxonomic levels within the Proteobacteria phylum have been correlated with colitis in a maternally transmitted fashion.

    “Species of lower taxonomic levels within the Proteobacteria phylum have been correlated with colitis in a maternally transmitted fashion 39.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Garrett WS, Gallini CA, Yatsunenko T, Michaud M, DuBois A, Delaney ML, Punit S, Karlsson M, Bry L, Glickman JN et al (2010) Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis. Cell Host Microbe 8: 292–300 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The microbiota influences the properties of the mucus barrier, and this can be observed within the same animal house with animals of identical genetic background.

    “It is obvious from this study that the microbiota influences the properties of the mucus barrier and that this can be observed within the same animal house with animals of identical genetic background.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The microbiota mucus sample strategy used may have reduced the observed differences in mucus microbiota because the amounts of attached mucus were not controlled for.

    “The microbiota mucus sample strategy used may have reduced the observed differences in mucus microbiota as the amounts of attached mucus were not controlled for.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In core 1 deficient mice, the inner mucus layer was more vulnerable and quickly dissolved, allowing bacteria to reach the epithelium and trigger inflammation.

    “In especially the core 1 deficient mice, the inner mucus layer was more vulnerable and quickly dissolved allowing bacteria to reach the epithelium and by this trigger inflammation 19.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Fu J, Wei B, Wen T, Johansson ME, Liu X, Bradford E, Thomsson KA, McGee S, Mansour L, Tong M et al (2011) Loss of intestinal core 1‐derived O‐glycans causes spontaneous colitis in mice. J Clin Invest 121: 1657–1666 source

      Not checked in the free run.

56 of 56

  • The paper relies on this without support.

    The two C57BL/6 colonies are genetically identical.

    “It also highlights that genetically identical animals housed in the same facility can have rather distinct microbiotas and barrier structures.”

  • The paper relies on this without support.

    Before this study, the possibility that microbiota stimulates the host to develop a more protective mucus layer had not been explored.

    “The possibility that the microbiota stimulates the host to develop a mucus layer with improved protective properties has not been explored.”

  • The paper relies on this without support.

    Colonization of germ-free mice with caecal microbiota from a room reproduces that room's relevant microbiota composition.

    “germ-free mice were colonized with caecal microbiota from mice in the two rooms.”

  • The paper relies on this without support.

    Housing colonized germ-free mice in the corresponding room does not introduce room-specific effects that confound the mucus phenotype.

    “The separate groups of colonized mice were subsequently housed in either room.”

  • The paper relies on this without support.

    Free-living wild mice provide a valid reference for a normal protective colon mucus phenotype.

    “The mucus phenotypes were compared with wild normally free-living mice caught in their natural habitat to elucidate the protective properties of natural occurring mucus.”

  • The paper relies on this without support.

    The gut microbiota is required for gut inflammation.

    “The gut microbiota is a prerequisite for inflammation in the gut and an imbalance in the microbiota in patients with inflammatory bowel disease (IBD) has been suggested 35.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The presence of bacteria along the GI tract is critical for the maintenance of the intestinal barrier.

    “The presence of bacteria along the GI tract is critical for the maintenance of the intestinal barrier, which facilitates the exchange of nutrients, water, and electrolytes and prevents the passage of harmful substances and pathogens from the intestinal lumen into the bloodstream (Jakobsson et al., 2015).”

    From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as Jakobsson et al., 2015

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Ki67 result cites the lamina propria panel

    Minor

    The text cites Fig. 4F for the increase in Ki67-labelled cells, but the figure caption identifies panel F as the lamina propria cell count. It assigns the Ki67-positive cell count to panel G.

  • Helicobacteraceae genus exceeds its reported class abundance

    Minor

    For Room 2 distal colon lumen, Table 1 reports 1% for the Helicobacteraceae genus but only 0.02% for its parent class, Epsilonproteobacteria. A genus cannot have greater relative abundance than the class containing it.

  • Immune-cell count cites the Ki67 panel

    Minor

    The text cites Fig. 4G for the lamina propria immune-cell count, but the figure caption identifies panel G as the Ki67-positive cell count. The caption assigns the lamina propria count to panel F.

3 of 3

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Jakobsson, H. E., Rodríguez‐Piñeiro, A. M., Schütte, A., Ermund, A., Boysen, P., Bemark, M., Sommer, F., Bäckhed, F., Hansson, G. C., & Johansson, M. E.
Affiliations
  • University of Gothenburg (SE)
  • Norwegian University of Life Sciences (NO)
  • Sahlgrenska University Hospital (SE)
Corresponding author
Johansson, Malin EV
ORCID
Venue
The EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2014-12-18
Volume
16
Issue
2
Pages
164-177
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
DOI
10.15252/embr.201439263
PMC
PMC4328744
OpenAlex
W2103108588
Cited by
700
References
73
Citations by year
2026: 29 · 2025: 38 · 2024: 67 · 2023: 58 · 2022: 103 · 2021: 93 · 2020: 78 · 2019: 65 · 2018: 52 · 2017: 49 · 2016: 37 · 2015: 31
FWCI
15.98
Type
journal article
Language
en
Update notices
addendum (2015-08-25)
Open access
Licence
Locations
  • EMBO Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Swedish Research Council (7461, 21027, 22220‐01‐5)
  • The Sahlgrenska Academy
  • National Institute of Allergy and Infectious Diseases (U01AI095473, U01AI095776‐03:9006862)
  • The Swedish Cancer Foundation
  • The Knut and Alice Wallenberg Foundation
  • IngaBritt and Arne Lundberg Foundation
  • Sahlgren's University Hospital
  • Wilhelm and Martina Lundgren's Foundation
  • Assar Gabrielsson's foundation
  • Clas Groschinskys foundation
  • Torsten och Ragnar Söderbergs Stiftelser
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, mucus permeability, mucus layer thickness, Proteobacteria, germ-free mice, C57BL/6 mice, host-microbe interactions
MeSH terms
Animals, Female, Intestinal Mucosa, Mice, Inbred C57BL, Mucus, RNA, Ribosomal, 16S, Specific Pathogen-Free Organisms, Mice, Microbiota

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review