Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases
Open accessAbstract
BACKGROUND: Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. We sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. METHODS: Adult male C57Bl/6 mice, germ-free, Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for 4 weeks. Fecal samples were collected for gut microbiota analysis through 16S rRNA terminal restriction fragment length polymorphism and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. Germ-free mice were conventionalized with gut microbes from treated and nontreated groups to determine their functional capacities in recipient hosts. RESULTS: Exposure to dexamethasone in wild-type mice led to substantial shifts in gut microbiota over a 4-week period. Furthermore, a significant downregulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a proinflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pretreated with dexamethasone, however, ameliorated symptoms of inflammation. CONCLUSIONS: Commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after glucocorticoid exposure. These findings underscore the notion that intestinal microbes comprise a "microbial organ" essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.
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Written from the paper’s full text.
TL;DR
In mice, dexamethasone reshapes the gut microbiota and alters colonic mucin gene expression, with DEX-altered microbiota conferring anti-inflammatory effects in a genetically susceptible colitis model. The findings suggest that glucocorticoid anti-inflammatory effects in the large intestine may be partly mediated by gut bacteria.
Key findings
- DEX exposure caused substantial, persistent gut microbiota shifts in both acute (10 days) and chronic (4 weeks) models; *Bifidobacterium* and *Lactobacillus* were significantly elevated after DEX, while the mucin degrader *Mucispirillum* was noticeably absent.
- DEX significantly down-regulated colonic *Muc2*, *Muc1*, and *Muc3* expression in the proximal colon of SPF mice, but distal colon expression did not differ significantly; GF mice treated with DEX alone showed no significant mucin gene changes, whereas conventionalization with DEX-treated donor microbiota significantly increased *Muc1* and *Muc2* in the proximal large intestine.
- Muc2-KO mice harbored a distinct microbiota with a trend toward greater Proteobacteria and, after DEX, increased Clostridiales and decreased Lactobacillaceae, though these patterns were not statistically significant; this microbiota was colitogenic upon transfer.
- In GF IL10-KO recipients, saline-treated donor microbiota caused marked body weight decrease, lower *Muc2* expression, and significant increases in IL12p40 and IL17; DEX-treated donor microbiota did not confer an inflammatory milieu to the same degree, and Muc2-KO donor microbiota produced lower body weights regardless of DEX or saline treatment.
Methods
- Adult male C57Bl/6 mice—WT, germ-free, Muc2-heterozygote, or Muc2-knockout—were injected i.p. with DEX at 1 mg/kg once daily for 10 days (acute) or 5 mg/kg once every 3 days for 4 weeks (chronic); controls received sterile saline.
- Fecal and cecal samples were analyzed by 16S rRNA T-RFLP and Illumina amplicon sequencing of the 515–806 bp region; colonic mucosal scrapings were used for mucin gene expression by quantitative real-time PCR, and mesenteric lymph nodes/mucosa for cytokine ELISA.
- GF WT or IL10-KO mice were conventionalized by oral gavage with cecal contents from DEX- or saline-treated donors; statistical analysis used Student’s t-test, one-way ANOVA, and Tukey post-hoc tests with significance at P < 0.05.
Limitations
- The paper states that some Muc2-KO microbiota patterns—increased Clostridiales and decreased Lactobacillaceae—were not statistically significant, and it calls for further studies delineating the complex regulatory network of mucin synthesis.
- No formal limitations section is stated. Evident from the text: all experiments are in mouse models, with no human IBD patient data; sample sizes are not reported in the provided text; and some conclusions rely on trends or transfer experiments in a single susceptible model.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 62 cited sources checked · 0 supported · 0 flagged
- Findingown data
Significant increases in IL12p40 and IL17 were observed in all recipients conventionalized with saline-treated microbiota.
“When inflammatory cytokine levels in MLNs and mucosal scrapings were examined, significant increases in IL12p40 and IL17 were observed in all recipients that were conventionalized with saline-treated microbiota.”
Quote in the paperSubstantial claim- Rests on an assumption: Germ-free IL10-KO mice do not develop colitis unless they are exposed to bacteria.
- Rests on an assumption: IL10-KO mice spontaneously develop colitis at a rate of 20–30% in the SPF animal facility.
- Findingown data
Conventionalizing GF mice with microbiota from DEX-treated donors led to a significant increase in both Muc1 and Muc2 expression in the proximal large intestine.
“However, conventionalizing GF mice with microbiota from DEX-treated donors led to a significant increase in both Muc1 and Muc2 expression in the proximal large intestine (Fig. 5) suggesting a key role for gut microbiota in the regulation of colonic mucin synthesis.”
Quote in the paperSubstantial claim- Rests on an assumption: Residual DEX in cecal contents from DEX-treated donors does not account for the anti-inflammatory effects observed in conventionalized recipients.
- Findingown data
DEX exposure in WT mice led to substantial shifts in gut microbiota over a four-week period.
“Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period.”
- Also stated in: § DEX treatment alters gut microbiota communities · plain
“T-RFLP analysis of fecal samples revealed a substantial shift in gut microbiota after DEX treatment.”
- Also stated in: § DISCUSSION · boosted
“Our results demonstrate that exposing healthy SPF mice to the GC DEX, both acutely (10 days) or chronically (over 4 weeks), leads to a dramatic shift in gut microbiota that persist throughout the length of the study.”
Quote in the paperSubstantial claim - Also stated in: § DEX treatment alters gut microbiota communities · plain
- Findingown data
In GF mice chronically treated with DEX, no significant changes in mucin gene expression were observed between DEX and control groups.
“Interestingly, no significant changes in mucin gene expression were observed between DEX and control groups.”
Quote in the paperSubstantial claim - Findingown data
IL10-KO mice conventionalized with saline-treated cecal contents exhibited a marked decrease in body weight compared to their DEX-conventionalized counterparts.
“IL10-KO mice conventionalized with saline-treated cecal contents exhibited a marked decrease in body weight when compared to their respective DEX-conventionalized counterparts (Fig. 8A).”
Quote in the paperSubstantial claim- Rests on an assumption: Germ-free IL10-KO mice do not develop colitis unless they are exposed to bacteria.
- Rests on an assumption: IL10-KO mice spontaneously develop colitis at a rate of 20–30% in the SPF animal facility.
- Findingown data
Mice conventionalized with Muc2-KO microbiota, irrespective of donor treatment, had lower body weights relative to those conventionalized with wild-type or heterozygote microbiota.
“Mice conventionalized with Muc2-KO microbiota, irrespective of the donor’s treatment (DEX or saline), had lower body weights relative to those conventionalized with wild-type or heterozygote microbiota (Fig. 8A).”
Quote in the paperSubstantial claim- Rests on an assumption: Germ-free IL10-KO mice do not develop colitis unless they are exposed to bacteria.
- Rests on an assumption: IL10-KO mice spontaneously develop colitis at a rate of 20–30% in the SPF animal facility.
- Findingown data
Conventionalization with saline-treated microbiota led to a pronounced decrease in Muc2 gene expression relative to DEX-treated donor microbiota.
“Interestingly, conventionalization with saline-treated microbiota led to a pronounced decrease in Muc2 gene expression relative to DEX-treated donor microbiota (Fig. 8B).”
Quote in the paperSubstantial claim- Rests on an assumption: Residual DEX in cecal contents from DEX-treated donors does not account for the anti-inflammatory effects observed in conventionalized recipients.
- Findingown data
Bifidobacterium was significantly elevated after DEX treatment.
“The Actinobacteria genus, Bifidobacterium, was significantly elevated after DEX treatment (Fig. 3A).”
Quote in the paperSubstantial claim - Findingown data
Mucispirillum was noticeably absent after DEX treatment.
“On the other hand, a specific genus of gut bacteria known to be a colonic mucin degrader, Mucispirillum, was noticeably absent after treatment with DEX (Fig. 3C), suggesting a possible relationship between GC, altered gut microbiota, and mucin regulation in the intestine.”
Quote in the paperSubstantial claim - Findingown data
Muc2-KO mice retained a microbiota distinct from those of their heterozygote and wild-type counterparts.
“However, Muc2-KO mice retained a microbiota distinct from those of their heterozygote and wild-type counterparts (circled, Fig. 6A).”
Quote in the paperSubstantial claim - Findingown data
DEX-treated donors did not confer an inflammatory milieu to the same degree as saline-treated donors.
“In contrast, DEX-treated donors did not confer an inflammatory milieu to the same degree (Fig. 8C).”
Quote in the paperSubstantial claim- Rests on an assumption: Residual DEX in cecal contents from DEX-treated donors does not account for the anti-inflammatory effects observed in conventionalized recipients.
- Findingown data
Amplicon sequencing of the 16S rRNA V4-5 region revealed phylogenetic shifts in gut microbiota after DEX exposure, notably in Actinobacteria.
“Amplicon sequencing of the 16S rRNA V4–5 region from fecal samples revealed phylogenetic shifts in gut microbiota after DEX exposure, notably in Actinobacteria (Fig. 2A,B).”
Quote in the paperSubstantial claim - Findingown data
Microbiota from mice exposed to DEX clustered distinctly from controls.
“Similar to earlier findings, microbiota from mice exposed to DEX clustered distinctly from controls.”
Quote in the paperSubstantial claim - Findingown data
Lactobacillus levels were increased after DEX treatment compared to controls.
“Furthermore, Lactobacillus levels were also increased when compared to controls (Fig. 3B).”
Quote in the paperNot a substantial claim - Findingown data
A trend toward a greater relative proportion of Proteobacteria was observed in Muc2-KO mice despite DEX treatment.
“A trend toward a greater relative proportion of Proteobacteria, a phyla commonly associated with inflammation, was observed in Muc2-KO mice despite DEX treatment.”
Quote in the paperSubstantial claim - Findingown data
16S rRNA amplicon sequencing revealed a trend toward greater prevalence of Proteobacteria in Muc2-KO mice.
“Bacterial 16S rRNA amplicon sequencing revealed a trend toward greater prevalence of Proteobacteria in Muc2-KO mice.”
Quote in the paperNot a substantial claim - Findingown data
Conventionalizing germ-free mice with microbiota from DEX-treated donors significantly increased Muc2 expression relative to controls.
“When GF mice were conventionalized with microbiota from DEX-treated donors, we observed a significant increase in Muc2 expression relative to controls.”
- Also stated in: § IL10-KO mice conventionalized with altered microbiota from DEX- or saline-treated donors · plain
“This finding corroborates our previous observations that conventionalizing GF mice with DEX-treated donor microbiota resulted in a significant up-regulation of Muc2 gene expression.”
Quote in the paperSubstantial claim - Also stated in: § IL10-KO mice conventionalized with altered microbiota from DEX- or saline-treated donors · plain
- Findingown data
In germ-free mice, DEX treatment alone produced no significant difference in mucin expression compared with controls.
“Interestingly, GF mice treated with DEX alone exhibited no significant difference in mucin expression relative to controls.”
Quote in the paperSubstantial claim - Findingown data
In DEX-treated mice, Mucispirillum (a mucin-reliant gut microbe) was noticeably absent.
“Interestingly, we observed a noticeable absence of Mucispirillum, a mucin-reliant gut microbe, in DEX-treated mice.”
Quote in the paperSubstantial claim - Findingown data
Muc2-KO mice clustered distinctly from heterozygote and wild-type counterparts.
“While DEX-treated mice clearly clustered from saline-treated controls, Muc2-KO mice also clustered distinctly from their heterozygote and wild-type counterparts.”
Quote in the paperSubstantial claim - Findingown data
DEX treatment significantly decreased mucin gene expression.
“Our results showed a significant decrease in mucin gene expression after DEX treatment.”
- Also stated in: § IL10-KO mice conventionalized with altered microbiota from DEX- or saline-treated donors · plain
“We reported earlier that DEX treatment in SPF mice significantly lowered Muc2 gene expression”
Quote in the paperSubstantial claim - Also stated in: § IL10-KO mice conventionalized with altered microbiota from DEX- or saline-treated donors · plain
- Findingown data
DEX-treated mice clustered separately from saline-treated controls.
“While DEX-treated mice clearly clustered from saline-treated controls, Muc2-KO mice also clustered distinctly from their heterozygote and wild-type counterparts.”
Quote in the paperSubstantial claim - Findingown data
The microbiota from DEX-treated SPF mice retains the greatest level of Muc2 expression after conventionalization.
“but show here that this microbiota retains the greatest level of Muc2 expression after conventionalization (Fig. 8B).”
Quote in the paperSubstantial claim - Findingown data
Pro-inflammatory cytokine levels (IL12p40, IL17) in both mucosal and mesenteric lymph nodes were significantly lower in DEX-exposed donors relative to controls.
“we found pro-inflammatory cytokine levels (IL12p40, IL17) in both mucosal and mesenteric lymph nodes to be significantly lower in donors exposed to DEX relative to controls.”
Quote in the paperSubstantial claim - Findingown data
DEX-treated Muc2-KO donor microbiota were more colitogenic compared to both wild-type and Muc2-heterozygote cohorts.
“Notably, DEX-treated Muc2-KO donor microbiota were more colitogenic compared to both wild-type and Muc2-heterozygote cohorts”
Quote in the paperSubstantial claim - Findingown data
IL10-KO mice conventionalized with saline-treated donor microbiota showed a considerable decrease in body weight relative to those given DEX-treated donor microbiota.
“IL10-KO mice conventionalized with saline-treated donor microbiota exhibited both a considerable decrease in body weight as well as significantly lower Muc2 gene expression levels relative to their DEX-treated donor counterparts.”
Quote in the paperSubstantial claim - Findingown data
IL10-KO mice conventionalized with saline-treated donor microbiota showed significantly lower Muc2 gene expression relative to those given DEX-treated donor microbiota.
“IL10-KO mice conventionalized with saline-treated donor microbiota exhibited both a considerable decrease in body weight as well as significantly lower Muc2 gene expression levels relative to their DEX-treated donor counterparts.”
Quote in the paperSubstantial claim - Findingnone given
The inherent microbiota from Muc2-KO mice is acutely colitogenic.
“We also report that the inherent microbiota from Muc2-KO mice is acutely colitogenic”
Quote in the paperSubstantial claim - Findingnone given
DEX-mediated shifts in gut bacteria confer a protective effect on the development of colonic inflammation when these microbes are conventionalized into the IL10-KO mouse model.
“However, DEX-mediated shifts in gut bacteria confer a protective effect on the development of colonic inflammation when these microbes are conventionalized into the IL10-KO mouse model.”
Quote in the paperSubstantial claim - Premisecitation
Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions.
“Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions.”
- Also stated in: § INTRODUCTION · plain
“Commensal gut bacteria provide a multitude of beneficial effects to the host which, include producing essential nutrients, metabolizing otherwise indigestible food components, educating the host immune system, strengthening gut barrier integrity, and other functions.1”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [1] Round JL Mazmanian SK The gut microbiota shapes intestinal immune responses during health and disease Nat Rev Immunol 2009 9 313 323 19343057 PMC4095778 source
Not checked in the free run.
- cites [2] Devaraj S Hemarajata P Versalovic J The human gut microbiome and body metabolism: implications for obesity and diabetes Clinical Chemistry 2013 59 617 628 23401286 PMC3974587 source
Not checked in the free run.
- cites [3] Cerf-Bensussan N Gaboriau-Routhiau Vr The immune system and the gut microbiota: friends or foes? Nat Rev Immunol 2010 10 735 744 20865020
Not checked in the free run.
- cites [4] Vijay-Kumar M Aitken JD Carvalho FA Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5 Science 2010 328 228 231 20203013 PMC4714868 source
Not checked in the free run.
- Also stated in: § INTRODUCTION · plain
- Interpretationown data
In the absence of Muc2, gut microbiota confer a pro-inflammatory, colitogenic phenotype.
“Altogether, these results suggest that in the absence of Muc2, gut microbiota confer a pro-inflammatory, colitogenic phenotype.”
Quote in the paperSubstantial claim- Rests on an assumption: Germ-free IL10-KO mice do not develop colitis unless they are exposed to bacteria.
- Rests on an assumption: IL10-KO mice spontaneously develop colitis at a rate of 20–30% in the SPF animal facility.
- Interpretationown data
Alterations in gut bacteria mediate the anti-inflammatory effects of GC exposure in the large intestine, as demonstrated in a genetically susceptible mouse model of colitis.
“Commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure.”
- Also stated in: § DISCUSSION · boosted
“Furthermore, these alterations in gut bacteria regulate the colonic inflammatory state in a genetically susceptible mouse model of colitis, demonstrating a gut microbe-mediated mechanism by which GCs apply their anti-inflammatory effects in the large intestine.”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse models and findings are relevant to human inflammatory bowel diseases and therapeutic approaches to restore intestinal homeostasis.
- Rests on an assumption: Residual DEX in cecal contents from DEX-treated donors does not account for the anti-inflammatory effects observed in conventionalized recipients.
- Also stated in: § DISCUSSION · boosted
- Premisecitation
Recent studies have suggested that GC signaling derives a portion of its effects through gut microbes.
“Recent studies have suggested that GC signaling derives a portion of its effects through gut microbes.21,22”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [21] Lutgendorff F Akkermans LMA Soderholm JD The role of microbiota and probiotics in stress-induced gastrointestinal damage Current Molecular Medicine 2008 8 282 298 18537636 source
Not checked in the free run.
- cites [22] O'Mahony SM Marchesi JR Scully P Early life stress alters behavior, immunity, and microbiota in rats: implications for Irritable Bowel Syndrome and psychiatric illnesses Biological Psychiatry 2009 65 263 267 18723164 source
Not checked in the free run.
- Premisecitation
Mice lacking the Muc2 gene develop spontaneous and experimentally-induced colitis.
“The importance of Muc2 in protecting the integrity of the gut epithelium is exemplified by the development of spontaneous and experimentally-induced colitis in mice lacking the Muc2 gene (Muc2-KO).14”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Velcich A Yang W Heyer J Colorectal cancer in mice genetically deficient in the mucin Muc2 Science 2002 295 1726 1729 11872843 source
Not checked in the free run.
- Premisecitation
A link between steroid hormones and gut microbiota has been implicated by the observation that altered gut microbiota can lead to substantial shifts in the HPA axis response to stress.
“For instance, a link between steroid hormones and gut microbiota has been implicated by the observation that altered gut microbiota can lead to substantial shifts in the hypothalamic-pituitary-adrenal (HPA) axis response to stress.33”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] Forsythe P Kunze WA Bienenstock J On communication between gut microbes and the brain Current Opinion in Gastroenterology 2012 28 557 562 23010679 source
Not checked in the free run.
- Premisecitation
A high-fat "Western" diet promotes the growth of otherwise rare pathobionts that can upset normal host-microbe relationships to trigger the development of experimental colitis in genetically-susceptible hosts.
“In addition, the consumption of a high-fat “Western” diet promotes the growth of otherwise rare pathobionts that can upset normal host-microbe relationships to trigger the development of experimental colitis in genetically-susceptible hosts.11”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Devkota S Wang Y Musch MW Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/−mice Nature 2012 487 104 108 22722865 PMC3393783
Not checked in the free run.
- Interpretationown data
DEX treatment in mice expressing the Muc2 gene alters gut microbiota to reduce inflammation in a genetically susceptible model of colitis.
“In contrast, DEX treatment in mice expressing the Muc2 gene alters gut microbiota to reduce inflammation in a genetically susceptible model of colitis.”
Quote in the paperSubstantial claim- Rests on an assumption: Residual DEX in cecal contents from DEX-treated donors does not account for the anti-inflammatory effects observed in conventionalized recipients.
- Rests on an assumption: Germ-free IL10-KO mice do not develop colitis unless they are exposed to bacteria.
- Rests on an assumption: IL10-KO mice spontaneously develop colitis at a rate of 20–30% in the SPF animal facility.
- Premisecitation
Antibiotics provide some IBD patients with therapeutic benefit.
“In support of this hypothesis, antibiotics provide some IBD patients with therapeutic benefit,10 underscoring the notion that gut bacteria play a key role in the etiopathology of this disease.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] Ohkusa T Kato K Terao S Newly developed antibiotic combination therapy for Ulcerative Colitis: a double-blind placebo-controlled multicenter trial Am J Gastroenterol 2010 105 1820 1829 20216533 source
Not checked in the free run.
- Premisecitation
Many studies have reported that alterations in the gut microbiota induce both pro- and anti-inflammatory effects in the host.
“Many studies have reported that alterations in the gut microbiota induce both pro- and anti-inflammatory effects in the host.5–7”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [5] Heimesaat MM Fischer A Siegmund B Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4 PLoS One 2007 2 e662 17653282 PMC1914380 source
Not checked in the free run.
- cites [6] Packey CD Sartor RB Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases Current opinion in infectious diseases 2009 22 292 19352175 PMC2763597 source
Not checked in the free run.
- cites [7] Cerf-Bensussan N Gaboriau-Routhiau V The immune system and the gut microbiota: friends or foes? Nat Rev Immunol 2010 10 735 744 20865020 source
Not checked in the free run.
- Interpretationown data
In this mouse model, genetics has a greater effect than DEX in coordinating the host-microbe dynamic.
“However, our results point toward a greater effect of genetics in coordinating the host-microbe dynamic in this mouse model.”
Quote in the paperSubstantial claim - Interpretationown data
Both endogenous and therapeutic GCs can affect the relationship between host and gut bacteria.
“Both endogenous and therapeutic GCs can affect this relationship.”
Quote in the paperSubstantial claim - Interpretationreasoning
Complete ablation of Muc2 imparts considerable pressures on the dynamics of bacterial colonization.
“it is of little surprise that the complete ablation of the predominant mucin expressed in the colon (Muc2) imparts considerable pressures on the dynamics of bacterial colonization.”
Quote in the paperSubstantial claim - Interpretationown data
DEX exposure has divergent effects on mucin regulation in the proximal large intestine of SPF versus GF mice.
“Our results suggest that exposure to DEX leads to divergent effects on mucin regulation in the proximal large intestine of SPF and GF mice.”
Quote in the paperSubstantial claim - Premisecitation
Reintroduction of microbes via conventionalization elevates intestinal mucin levels.
“Previous studies have reported that the reintroduction of microbes via conventionalization elevates mucin levels in the intestine.51,52”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [51] Meslin J-C Fontaine N Andrieux C Variation of mucin distribution in the rat intestine, caecum and colon: effect of the bacterial flora Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 1999 123 235 239 10501018 source
Not checked in the free run.
- cites [52] Deplancke B Gaskins HR Microbial modulation of innate defense: goblet cells and the intestinal mucus layer The American Journal of Clinical Nutrition 2001 73 1131S 1141S 11393191 source
Not checked in the free run.
- Interpretationreasoning
The microbiota of Muc2-KO mice has a pro-inflammatory milieu.
“altogether supporting the presence of a pro-inflammatory milieu within the microbiota of Muc2-KO mice.”
Quote in the paperSubstantial claim - Interpretationreasoning
The up-regulation of mucin expression after conventionalization is uninhibited because mucophilic bacteria are lacking in DEX-treated mice.
“these results are consistent with our hypothesis that the up-regulation of mucin expression due to conventionalization is now uninhibited due to the lack of mucophilic bacteria in these mice.”
Quote in the paperSubstantial claim - Premisecitation
Proteobacteria are intimately tied to a pro-inflammatory state.
“This phyla has been shown to be intimately tied to a pro-inflammatory state.11,60,61”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [11] Devkota S Wang Y Musch MW Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/−mice Nature 2012 487 104 108 22722865 PMC3393783 source
Not checked in the free run.
- cites [60] Mukhopadhya I Hansen R El-Omar EM IBD-what role do Proteobacteria play? Nat Rev Gastroenterol Hepatol 2012 9 219 230 22349170 source
Not checked in the free run.
- cites [61] Ramer-Tait A Overstreet A-M Hostetter J Colonization with distinct Proteobacteria provocateurs induces multifactorial gastrointestinal inflammation that is regulated by CD4+ T cells: P-194 Inflammatory Bowel Diseases 2012 18 S92
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning
The impact of glucocorticoid-mediated effects on host and microbiota is highly contextual.
“Based on these and other reports, we surmise that the impact of GC-mediated effects on host and microbiota is highly contextual.”
Quote in the paperNot a substantial claim - Premisecitation
Intestinal microbes have a considerable role in the pathogenesis of IBD.
“Previous studies have reported a multitude of genetic polymorphisms that either increase or lower the risk of developing IBD,30 while others have demonstrated a considerable role for intestinal microbes in their pathogenesis.1,31,32”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [1] Round JL Mazmanian SK The gut microbiota shapes intestinal immune responses during health and disease Nat Rev Immunol 2009 9 313 323 19343057 PMC4095778 source
Not checked in the free run.
- cites [31] Loh G Blaut M Role of commensal gut bacteria in inflammatory bowel diseases Gut microbes 2012 3 503 514 PMC3495792 23060017 source
Not checked in the free run.
- cites [32] Sartor RB Microbial influences in inflammatory bowel diseases Gastroenterology 2008 134 577 594 18242222 source
Not checked in the free run.
- Premisecitation
Gut microbiota can cause or contribute to a variety of metabolic, inflammatory, and immunologic diseases.
“On the other hand, gut microbiota can also cause or contribute to a variety of metabolic, inflammatory, and immunologic diseases.2–4”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [2] Devaraj S Hemarajata P Versalovic J The human gut microbiome and body metabolism: implications for obesity and diabetes Clinical Chemistry 2013 59 617 628 23401286 PMC3974587 source
Not checked in the free run.
- cites [3] Cerf-Bensussan N Gaboriau-Routhiau Vr The immune system and the gut microbiota: friends or foes? Nat Rev Immunol 2010 10 735 744 20865020
Not checked in the free run.
- cites [4] Vijay-Kumar M Aitken JD Carvalho FA Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5 Science 2010 328 228 231 20203013 PMC4714868 source
Not checked in the free run.
- Premisecitation
Prior studies have demonstrated up-regulation of mucins under pro-inflammatory settings.
“However, previous studies have demonstrated an up-regulation of mucins under pro-inflammatory settings,44,45”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [44] Blank M Klussmann E Krüger-Krasagakes S Expression of MUC2-mucin in colorectal adenomas and carcinomas of different histological types International Journal of Cancer 1994 59 301 306 7927933
Not checked in the free run.
- cites [45] Hanski C Hofmeier M Schmitt-Gräff A Overexpression or ectopic expression of MUC2 is the common property of mucinous carcinomas of the colon, pancreas, breast, and ovary The Journal of Pathology 1997 182 385 391 9306958
Not checked in the free run.
- Premisecitation
Mucin expression is critical for the growth and survival of gut bacteria.
“Since mucin expression is critical for the growth and survival of gut bacteria,58,59”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [58] Hoskins LC Mucin degradation in the human gastrointestinal tract and its significance to enteric microbial ecology European Journal of Gastroenterology & Hepatology 1993 5 205 213
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [59] Cummings JH Macfarlane GT The control and consequences of bacterial fermentation in the human colon Journal of Applied Bacteriology 1991 70 443 459 1938669 source
Not checked in the free run.
- Interpretationreasoning
In healthy mice, counter-regulatory pathways for mucosal homeostasis are more likely to be intact and able to compensate for reduced mucin expression.
“Additionally, counter-regulatory pathways for mucosal homeostasis are more likely to be intact and able to compensate for reduced mucin expression.”
Quote in the paperSubstantial claim - Interpretationreasoning
In healthy mice without pre-existing inflammatory or genetic conditions, decreased mucin expression due to DEX may still be sufficient to maintain intestinal homeostasis.
“In healthy mice without pre-existing inflammatory or genetic conditions, mucin expression even if decreased by DEX may be amply sufficient to maintain intestinal homeostasis.”
Quote in the paperNot a substantial claim - Premisecitation
IL10-KO mice develop colitis only in the presence of microbes.
“Notably, the IL10-KO mouse model only develops colitis in the presence of microbes,65”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [65] Sellon RK Tonkonogy S Schultz M Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice Infection and Immunity 1998 66 5224 5231 9784526 PMC108652
Not checked in the free run.
- Interpretationown data
Gut microbes in the absence of DEX can substantially affect colonic mucin expression.
“the presence of gut microbes in the absence of DEX can substantially affect their expression.”
Quote in the paperSubstantial claim - Premisecitation
Muc2-KO mice possess a distinct gut-associated bacterial community influenced by altered genetic and immune states.
“The Muc2-KO mouse possesses a distinct gut-associated bacterial community that is influenced by its altered genetic and immune states, as has been shown in other genetic knockout mouse models.4,53–55”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [4] Vijay-Kumar M Aitken JD Carvalho FA Metabolic syndrome and altered gut microbiota in mice lacking toll-like receptor 5 Science 2010 328 228 231 20203013 PMC4714868 source
Not checked in the free run.
- cites [53] Elinav E Strowig T Kau Andrew L NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis Cell 2011 145 745 757 21565393 PMC3140910 source
Not checked in the free run.
- cites [54] Henao-Mejia J Elinav E Jin C Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity Nature 2012 482 179 185 22297845 PMC3276682 source
Not checked in the free run.
- cites [55] Wen L Ley RE Volchkov PY Innate immunity and intestinal microbiota in the development of Type 1 diabetes Nature 2008 455 1109 1113 18806780 PMC2574766 source
Not checked in the free run.
- Interpretationown data
DEX exposure in the absence of gut microbes is not sufficient to regulate mucin gene expression.
“This lack of change in GF mice suggests to us that DEX alone is not sufficient to regulate mucin synthesis in the absence of gut microbes.”
- Also stated in: § IL10-KO mice conventionalized with altered microbiota from DEX- or saline-treated donors · hedged
“In contrast, DEX exposure in the absence of microbes is not presently sufficient to produce such an effect.”
Quote in the paperSubstantial claim - Also stated in: § IL10-KO mice conventionalized with altered microbiota from DEX- or saline-treated donors · hedged
- Premisecitation
Inflammation is closely associated with the presence or absence of these microbes (Clostridiales and Lactobacillaceae).
“Previous studies have shown a close association between inflammation and the presence or absence of these microbes, respectively,62–64”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [62] de La Serre CB Ellis CL Lee J Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation Am J Physiol Gastrointest Liver Physiol 2010 299 G440 G448 20508158 PMC2928532 source
Not checked in the free run.
- cites [63] Hoffmann C Hill DA Minkah N Community-wide response of the gut microbiota to enteropathogenic Citrobacter rodentium infection revealed by deep sequencing Infection and Immunity 2009 77 4668 4678 19635824 PMC2747949 source
Not checked in the free run.
- cites [64] Ventura M O'Flaherty S Claesson MJ Genome-scale analyses of health-promoting bacteria: probiogenomics Nat Rev Micro 2009 7 61 71 19029955 source
Not checked in the free run.
- Interpretationown data
Muc2-KO mice are comparatively refractory to DEX-induced changes in gut microbiota.
“reinforcing our earlier findings that Muc2-KO mice are comparatively refractory to DEX-induced changes in gut microbiota.”
Quote in the paperSubstantial claim - Interpretationown data
Chronic exposure to DEX shifts gut microbiota in varying degrees to regulate colonic mucin gene expression in mice under both healthy and diseased conditions.
“In summary, we have shown that chronic exposure to DEX shifts gut microbiota in varying degrees to regulate colonic mucin gene expression in mice under both healthy and diseased conditions.”
Quote in the paperSubstantial claim
- May combine two claims. 15
- Classified as probably not a substantial claim. 14
May combine two claims.
Findingown dataDEX-treated Muc2-KO mice showed increasing Clostridiales compared to DEX-treated Muc2-heterozygotes and a concomitant decrease in Lactobacillaceae, though these patterns were not statistically significant.
“Deeper phylogenetic analysis showed increasing Clostridiales in DEX-treated Muc2-KO mice compared to DEX-treated Muc2-heterozygotes and a concomitant decrease in Lactobacillaceae (Fig. 6B), though these patterns were not statistically significant.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataPCA revealed microbial-based clustering in DEX-treated animals, but not in saline-treated controls.
“Principal Component Analysis (PCA) revealed a microbial-based clustering in DEX-treated animals, but not in saline-treated controls (Fig. 1D).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe DEX-induced gut microbiota shift was evident in both acute (10 days) and chronic (28 days) treatment and persisted throughout the study.
“This shift was evident in both acute (10 days) and chronic (28 days) models of DEX treatment and persisted throughout the duration of the study (Fig. 1B,C).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMuc1 and Muc3 gene expression were also significantly lower after DEX in the proximal colon, but not in the distal colon.
“Gene expression levels of Muc1 and Muc3, which together constitute a minority of gut mucins, were also significantly lower after DEX. However, these differences were only evident in the proximal colon (Fig. 4A), as mucin gene expression in the distal colon was not significantly different between DEX- and saline-treated mice (Fig. 4B).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn DEX-treated mice, Muc2 gene expression was significantly lower in the proximal colon, but not in the distal colon.
“Quantitative real-time PCR results showed that Muc2 gene expression was significantly lower in DEX-treated mice.”
- Also stated in: § Mucin gene expression decreases after exposure to DEX · plain
“However, these differences were only evident in the proximal colon (Fig. 4A), as mucin gene expression in the distal colon was not significantly different between DEX- and saline-treated mice (Fig. 4B).”
Quote in the paperNot a substantial claim- Also stated in: § Mucin gene expression decreases after exposure to DEX · plain
May combine two claims.
Findingown dataMuc2-KO mice exhibited increased prevalence of Clostridiales, though not statistically significant.
“Furthermore, these mice also exhibited increased prevalence of Clostridiales alongside a concomitant decrease in Lactobacillaceae, though these patterns were not statistically significant.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMuc2-KO mice exhibited decreased prevalence of Lactobacillaceae, though not statistically significant.
“Furthermore, these mice also exhibited increased prevalence of Clostridiales alongside a concomitant decrease in Lactobacillaceae, though these patterns were not statistically significant.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataIntestinal microbes comprise a "microbial organ" essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.
“These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.”
Quote in the paperSubstantial claim- Rests on an assumption: The mouse models and findings are relevant to human inflammatory bowel diseases and therapeutic approaches to restore intestinal homeostasis.
May combine two claims.
PremisecitationPrevious studies have not identified specific gut microbes affected by GC exposure nor addressed the functional repercussions of GCs and altered gut microbiota.
“However, these studies have not identified specific gut microbes affected by GC exposure nor addressed the functional repercussions of GCs and altered gut microbiota.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Ünsal H Balkaya M Ünsal C The short-term effects of different doses of dexamethasone on the numbers of some bacteria in the ileum Digestive Diseases and Sciences 2008 53 1842 1845 18049898 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMucins constitute the major component of the mucus layer, and in the colon, Muc2 is the most prominent mucin expressed and secreted by goblet cells.
“Mucins constitute the major component of this mucus layer12 and in the colon, Muc2 is the most prominent mucin expressed and secreted by goblet cells.13”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [12] Forstner JF Forstner GG Gastrointestinal mucus Physiology of the gastrointestinal tract 1994 1255 1283
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [13] Tytgat KMAJ Buller HA Opdam FJM Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin Gastroenterology 1994 107 1352 1363 7926500 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationDEX is a synthetic, more potent GC routinely used as an anti-inflammatory, immunosuppressive agent.
“Dexamethasone (DEX), a synthetic, more potent GC, has been routinely used as an anti-inflammatory, immunosuppressive agent.17”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Friend Review article: issues in oral administration of locally acting glucocorticosteroids for treatment of inflammatory bowel disease Alimentary Pharmacology & Therapeutics 1998 12 591 603 9701522 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOne mechanism by which DEX resolves its anti-inflammatory effects is through a decrease in NF-κB activity.
“Previous work has shown that one mechanism by which DEX resolves its anti-inflammatory effects is through a decrease in NF-κB activity.18”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Scheinman RI Gualberto A Jewell CM Characterization of mechanisms involved in transrepression of NF-kappa B by activated glucocorticoid receptors Mol Cell Biol 1995 15 943 953 7823959 PMC231982 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationGCs are currently one of the most widely used first-line agents in the treatment of IBD.
“GCs are currently one of the most widely used first-line agents in the treatment of IBD.16”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Faubion WA Jr Loftus EV Jr Harmsen WS The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study Gastroenterology 2001 121 255 260 11487534 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDecreased Muc2 expression has been implicated in the etiopathogenesis of sporadic and IBD-associated colon cancers.
“Additionally, decreased Muc2 expression has been implicated in the etiopathogenesis of sporadic and IBD-associated colon cancers.14,15”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [14] Velcich A Yang W Heyer J Colorectal cancer in mice genetically deficient in the mucin Muc2 Science 2002 295 1726 1729 11872843 source
Not checked in the free run.
- cites [15] Xavier RJ Podolsky DK Unravelling the pathogenesis of inflammatory bowel disease Nature 2007 448 427 434 17653185 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationProlonged exposure to GCs can result in side effects including central adiposity, insulin resistance and gastrointestinal complications.
“However, prolonged exposure to GCs can result in various side effects, including central adiposity, insulin resistance and gastrointestinal complications.19,20”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [19] Gallant C Kenny P Oral glucocorticoids and their complications. A review J Am Acad Dermatol 1986 14 161 177 3512634 source
Not checked in the free run.
- cites [20] Heimdal K Hirschberg H Slettebà H High incidence of serious side effects of high-dose dexamethasone treatment in patients with epidural spinal cord compression Journal of Neuro-Oncology 1992 12 141 144 1560260 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationGCs have potent anti-inflammatory benefits.
“GCs have potent anti-inflammatory benefits,35,36 so the presence of Bifidobacteria and Lactobacillus, both previously associated with anti-inflammatory”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [35] Barnes PJ Anti-inflammatory actions of glucocorticoids: molecular mechanisms Clin Sci 1998 94 557 572 9854452 source
Not checked in the free run.
- cites [36] Smoak KA Cidlowski JA Mechanisms of glucocorticoid receptor signaling during inflammation Mechanisms of Ageing and Development 2004 125 697 706 15541765 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationGlucocorticoids tend to confer protective, anti-inflammatory effects.
“as GCs tend to confer protective, anti-inflammatory effects.36,41–43”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [36] Smoak KA Cidlowski JA Mechanisms of glucocorticoid receptor signaling during inflammation Mechanisms of Ageing and Development 2004 125 697 706 15541765 source
Not checked in the free run.
- cites [41] Nanthakumar NN Young C Ko JS Glucocorticoid responsiveness in developing human intestine: possible role in prevention of necrotizing enterocolitis Am J Physiol Gastrointest Liver Physiol 2005 288 G85 G92 15591589 source
Not checked in the free run.
- cites [42] Auphan N DiDonato JA Rosette C Immunosuppression by glucocorticoids: inhibition of NF-kB activity through induction of IkB synthesis Science 1995 270 286 290 7569976 source
Not checked in the free run.
- cites [43] Crinelli R Antonelli A Bianchi M Selective inhibition of NF-kB activation and TNF-a production in macrophages by red blood cell-mediated delivery of dexamethasone Blood Cells, Molecules, and Diseases 2000 26 211 222 10950941 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationMucins play a considerable role in the gut, namely in colonic protection.
“Since mucins play a considerable role in the gut, namely in colonic protection,28,40”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [28] Van der Sluis M De Koning BAE De Bruijn ACJM Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection Gastroenterology 2006 131 117 129 16831596 source
Not checked in the free run.
- cites [40] Kim YS Byrd JC Ulcerative colitis: a specific mucin defect? Gastroenterology 1984 87 1193 6479541 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationThe HPA axis is critical to proper glucocorticoid signaling.
“The HPA axis is critical to proper glucocorticoid signaling,50”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [50] Pariante CM Lightman SL The HPA axis in major depression: classical theories and new developments Trends in Neurosciences 2008 31 464 468 18675469 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOther studies report down-regulation of mucin expression.
“while others report a down-regulation of their expression.14”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [14] Velcich A Yang W Heyer J Colorectal cancer in mice genetically deficient in the mucin Muc2 Science 2002 295 1726 1729 11872843 source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable).
Interpretationown dataThe balance between host and bacteria can be mitigated through certain circumstances.
“Our studies show that the balance between host and bacteria can be mitigated through certain circumstances.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationHost biology and environmental cues are both substantial contributors to shaping gut-associated bacterial communities.
“Host biology and environmental cues are both substantial contributors toward shaping gut-associated bacterial communities.3,56,57”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [3] Cerf-Bensussan N Gaboriau-Routhiau Vr The immune system and the gut microbiota: friends or foes? Nat Rev Immunol 2010 10 735 744 20865020 source
Not checked in the free run.
- cites [56] Lozupone CA Stombaugh JI Gordon JI Diversity, stability and resilience of the human gut microbiota Nature 2012 489 220 230 22972295 PMC3577372 source
Not checked in the free run.
- cites [57] Ley RE Backhed F Turnbaugh P Obesity alters gut microbial ecology Proceedings of the National Academy of Sciences of the United States of America 2005 102 11070 11075 16033867 PMC1176910 source
Not checked in the free run.
May combine two claims.
PremisecitationDeclining body weight and colonic Muc2 expression are hallmark characteristics of colitis.
“Declining trends in both body weight as well as colonic Muc2 expression levels, among other traits, are hallmark characteristics of colitis.28”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Van der Sluis M De Koning BAE De Bruijn ACJM Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection Gastroenterology 2006 131 117 129 16831596 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrevious studies have reported genetic polymorphisms that either increase or lower the risk of developing IBD.
“Previous studies have reported a multitude of genetic polymorphisms that either increase or lower the risk of developing IBD,30 while others have demonstrated a considerable role for intestinal microbes in their pathogenesis.1,31,32”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] Lees CW Barrett JC Parkes M New IBD genetics: common pathways with other diseases Gut 2011 60 1739 1753 21300624 source
Not checked in the free run.
May combine two claims.
PremisecitationRodents treated with a single high-dose injection of DEX increased the number of ileal anaerobic bacteria while low-dose GC produced an increase in coliform bacteria.
“A study by Ünsal and colleagues showed that rodents treated with a single high-dose injection of DEX increased the number of ileal anaerobic bacteria while low-dose GC produced an increase in coliform bacteria,34 demonstrating a significant, acute effect of GC exposure on gut microbes.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Ünsal H Balkaya M Ünsal C The short-term effects of different doses of dexamethasone on the numbers of some bacteria in the ileum Digestive Diseases and Sciences 2008 53 1842 1845 18049898 source
Not checked in the free run.
May combine two claims.
Interpretationown dataGut microbiota are necessary and sufficient to regulate mucin gene expression.
“Our results highlight the notion that gut microbiota are necessary and sufficient to regulate mucin gene expression.”
Quote in the paperSubstantial claim
The paper relies on this without support.
Physiological and pharmacological levels of glucocorticoids can profoundly affect mucus production and secretion.
“Physiological and pharmacological levels of glucocorticoids (GCs) can profoundly affect mucus production and secretion.”
The paper relies on this without support.
The mouse models and findings are relevant to human inflammatory bowel diseases and therapeutic approaches to restore intestinal homeostasis.
“These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.”
The paper relies on this without support.
Residual DEX in cecal contents from DEX-treated donors does not account for the anti-inflammatory effects observed in conventionalized recipients.
“cecal contents from DEX- or saline-treated Muc2-KO mice were conventionalized into GF IL10-KO mice (Fig. 7).”
The paper relies on this without support.
Germ-free IL10-KO mice do not develop colitis unless they are exposed to bacteria.
“However, germ-free IL10-KO mice do not develop colitis unless they are exposed to bacteria, suggesting a microbe-driven component mediating this effect.”
The paper relies on this without support.
IL10-KO mice spontaneously develop colitis at a rate of 20–30% in the SPF animal facility.
“These conventionalized recipient mice are used as a model of genetic susceptibility to colitis, as they spontaneously develop colitis at a rate of 20–30% in our SPF animal facility.”
The paper relies on this without support.
The mucus layer overlying the gut epithelium plays a key role in establishing the mutualistic relationship between host and microbe.
“The mucus layer that overlies the gut epithelium plays a key role in establishing this mutualistic relationship between host and microbe.”
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?
Effects of glucocorticoids on the composition and functioning of the microbiota vary, with some studies indicating disruption and others showing beneficial effects, likely depending on the degree of exposure (dose and period) and the type of glucocorticoid studied.
“Regarding the effects of glucocorticoids on the composition and functioning of the microbiota, some studies have indicated microbiota disruption, while others have shown beneficial effects, which likely depend on the degree of exposure (dose and period) and the type of glucocorticoid studied (434–437)”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [437]
Cites
Obesity alters gut microbial ecology
Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., & Gordon, J. I. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504978102 · Cited by 6,176 · see citing works
Diversity, stability and resilience of the human gut microbiota
Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K., & Knight, R. (2012) · Nature · doi:10.1038/nature11550 · Cited by 5,533 · see citing works
The gut microbiota shapes intestinal immune responses during health and disease
Round, J. L., & Mazmanian, S. K. (2009) · Nature Reviews Immunology · doi:10.1038/nri2515 · Cited by 5,029 · see citing works
Unravelling the pathogenesis of inflammatory bowel disease
Xavier, R. J., & Podolsky, D. K. (2007) · Nature · doi:10.1038/nature06005 · Cited by 4,364 · see citing works
Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X., Kubo, C., & Koga, Y. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.063388 · Cited by 2,735 · see citing works
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
Henao-Mejia, J., Elinav, E., Jin, C., Hao, L., Mehal, W. Z., Strowig, T., Thaiss, C. A., Kau, A. L., Eisenbarth, S. C., Jurczak, M. J., et al. (2012) · Nature · doi:10.1038/nature10809 · Cited by 2,435 · see citing works
Auphan, N., DiDonato, J. A., Rosette, C., Helmberg, A., & Karin, M. (1995) · Science · doi:10.1126/science.270.5234.286 · Cited by 2,390 · see citing works
The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria
Johansson, M. E. V., Phillipson, M., Petersson, J., Velcich, A., Holm, L., & Hansson, G. C. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803124105 · Cited by 2,200 · see citing works
Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5
Vijay-Kumar, M., Aitken, J. D., Carvalho, F. A., Cullender, T. C., Mwangi, S., Srinivasan, S., Sitaraman, S. V., Knight, R., Ley, R. E., & Gewirtz, A. T. (2010) · Science · doi:10.1126/science.1179721 · Cited by 2,068 · see citing works
NLRP6 Inflammasome Regulates Colonic Microbial Ecology and Risk for Colitis
Elinav, E., Strowig, T., Kau, A. L., Henao-Mejia, J., Thaiss, C. A., Booth, C. J., Peaper, D. R., Bertin, J., Eisenbarth, S. C., Gordon, J. I., et al. (2011) · Cell · doi:10.1016/j.cell.2011.04.022 · Cited by 2,024 · see citing works
The HPA axis in major depression: classical theories and new developments
Pariante, C. M., & Lightman, S. L. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.006 · Cited by 2,009 · see citing works
Microbial Influences in Inflammatory Bowel Diseases
Sartor, R. B. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.11.059 · Cited by 1,927 · see citing works
Innate immunity and intestinal microbiota in the development of Type 1 diabetes
Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., et al. (2008) · Nature · doi:10.1038/nature07336 · Cited by 1,921 · see citing works
Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice
Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D. A., Jabri, B., & Chang, E. B. (2012) · Nature · doi:10.1038/nature11225 · Cited by 1,904 · see citing works
Van der Sluis, M., De Koning, B. A. E., De Bruijn, A. C. J. M., Velcich, A., Meijerink, J. P. P., Van Goudoever, J. B., Büller, H. A., Dekker, J., Van Seuningen, I., Renes, I. B., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.04.020 · Cited by 1,684 · see citing works
Anti-inflammatory Actions of Glucocorticoids: Molecular Mechanisms
Barnes, P. J. (1998) · Clinical Science · doi:10.1042/cs0940557 · Cited by 1,591 · see citing works
The control and consequences of bacterial fermentation in the human colon
Cummings, J. H., & Macfarlane, G. T. (1991) · Journal of Applied Bacteriology · doi:10.1111/j.1365-2672.1991.tb02739.x · Cited by 1,499 · see citing works
Sellon, R. K., Tonkonogy, S., Schultz, M., Dieleman, L. A., Grenther, W., Balish, E., Rennick, D. M., & Sartor, R. B. (1998) · Infection and Immunity · doi:10.1128/iai.66.11.5224-5231.1998 · Cited by 1,483 · see citing works
Neufeld, K. M., Kang, N., Bienenstock, J., & Foster, J. A. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2010.01620.x · Cited by 1,392 · see citing works
Faubion, W. A., Loftus, E. V., Harmsen, W. S., Zinsmeister, A. R., & Sandborn, W. J. (2001) · Gastroenterology · doi:10.1053/gast.2001.26279 · Cited by 1,144 · see citing works
O'Mahony, S. M., Marchesi, J. R., Scully, P., Codling, C., Ceolho, A.-M., Quigley, E. M. M., Cryan, J. F., & Dinan, T. G. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.026 · Cited by 1,069 · see citing works
Microbial modulation of innate defense: goblet cells and the intestinal mucus layer
Deplancke, B., & Gaskins, H. R. (2001) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/73.6.1131s · Cited by 1,012 · see citing works
de La Serre, C. B., Ellis, C. L., Lee, J., Hartman, A. L., Rutledge, J. C., & Raybould, H. E. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00098.2010 · Cited by 949 · see citing works
Colorectal Cancer in Mice Genetically Deficient in the Mucin Muc2
Velcich, A., Yang, W., Heyer, J., Fragale, A., Nicholas, C., Viani, S., Kucherlapati, R., Lipkin, M., Yang, K., & Augenlicht, L. (2002) · Science · doi:10.1126/science.1069094 · Cited by 936 · see citing works
Scheinman, R. I., Gualberto, A., Jewell, C. M., Cidlowski, J. A., & Baldwin, A. S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.2.943 · Cited by 819 · see citing works
IBD—what role do Proteobacteria play?
Mukhopadhya, I., Hansen, R., El-Omar, E. M., & Hold, G. L. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.14 · Cited by 810 · see citing works
Furrie, E., Macfarlane, S., Kennedy, A., Cummings, J. H., Walsh, S. V., O’Neil, D. A., & Macfarlane, G. T. (2005) · Gut · doi:10.1136/gut.2004.044834 · Cited by 766 · see citing works
Lactobacillus species prevents colitis in interleukin 10 gene–deficient mice
Madsen, K. L., Doyle, J. S. G., Jewell, L. D., Tavernini, M. M., & Fedorak, R. N. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70013-2 · Cited by 761 · see citing works
The immune system and the gut microbiota: friends or foes?
Cerf-Bensussan, N., & Gaboriau-Routhiau, V. (2010) · Nature Reviews Immunology · doi:10.1038/nri2850 · Cited by 704 · see citing works
New IBD genetics: common pathways with other diseases
Lees, C. W., Barrett, J. C., Parkes, M., & Satsangi, J. (2011) · Gut · doi:10.1136/gut.2009.199679 · Cited by 635 · see citing works
Bloom, S. M., Bijanki, V. N., Nava, G. M., Sun, L., Malvin, N. P., Donermeyer, D. L., Dunne, W. M., Allen, P. M., & Stappenbeck, T. S. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.04.009 · Cited by 488 · see citing works
Genome-scale analyses of health-promoting bacteria: probiogenomics
Ventura, M., O'Flaherty, S., Claesson, M. J., Turroni, F., Klaenhammer, T. R., van Sinderen, D., & O'Toole, P. W. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2047 · Cited by 471 · see citing works
Redinbaugh, M. G., & Turley, R. B. (1986) · Analytical Biochemistry · doi:10.1016/0003-2697(86)90091-6 · Cited by 447 · see citing works
Mechanisms of glucocorticoid receptor signaling during inflammation
Smoak, K. A., & Cidlowski, J. A. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.06.010 · Cited by 420 · see citing works
T-REX: software for the processing and analysis of T-RFLP data
Culman, S. W., Bukowski, R., Gauch, H. G., Cadillo‐Quiroz, H., & Buckley, D. H. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-171 · Cited by 410 · see citing works
The Human Gut Microbiome and Body Metabolism: Implications for Obesity and Diabetes
Devaraj, S., Hemarajata, P., & Versalovic, J. (2013) · Clinical Chemistry · doi:10.1373/clinchem.2012.187617 · Cited by 321 · see citing works
Packey, C. D., & Sartor, R. B. (2009) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0b013e32832a8a5d · Cited by 319 · see citing works
Biosynthesis of human colonic mucin: Muc2 is the prominent secretory mucin
Tytgat, K. M. A. J., Büller, H. A., Opdam, F. J. M., Kim, Y. S., Einerhand, A. W. C., & Dekker, J. (1994) · Gastroenterology · doi:10.1016/0016-5085(94)90537-1 · Cited by 241 · see citing works
The Role of Microbiota and Probiotics in Stress-Induced Gastrointestinal Damage
Lutgendorff, F., Akkermans, L., & Soderholm, J. (2008) · Current Molecular Medicine · doi:10.2174/156652408784533779 · Cited by 230 · cited 1× · see citing works
“Recent studies have suggested that GC signaling derives a portion of its effects through gut microbes.(20,21) Because many mechanisms of GC action are not well described, it was of interest to explore the cross talk between GCs, the intestinal microbiota, and colonic physiology.”
BackgroundHeimesaat, M. M., Fischer, A., Siegmund, B., Kupz, A., Niebergall, J., Fuchs, D., Jahn, H.-K., Freudenberg, M., Loddenkemper, C., Batra, A., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000662 · Cited by 213 · see citing works
Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-κB activation
Riedel, C. U. (2006) · World Journal of Gastroenterology · doi:10.3748/wjg.v12.i23.3729 · Cited by 210 · see citing works
The Role of Microbes in Crohn's Disease
Eckburg, P. B., & Relman, D. A. (2006) · Clinical Infectious Diseases · doi:10.1086/510385 · Cited by 206 · see citing works
Role of commensal gut bacteria in inflammatory bowel diseases
Loh, G., & Blaut, M. (2012) · Gut Microbes · doi:10.4161/gmic.22156 · Cited by 177 · see citing works
Heimdal, K., Hirschberg, H., Sletteb�, H., Watne, K., & Nome, O. (1992) · Journal of Neuro-Oncology · doi:10.1007/bf00172664 · Cited by 173 · see citing works
Hoffmann, C., Hill, D. A., Minkah, N., Kirn, T., Troy, A., Artis, D., & Bushman, F. (2009) · Infection and Immunity · doi:10.1128/iai.00493-09 · Cited by 142 · see citing works
Ohkusa, T., Kato, K., Terao, S., Chiba, T., Mabe, K., Murakami, K., Mizokami, Y., Sugiyama, T., Yanaka, A., Takeuchi, Y., et al. (2010) · American Journal of Gastroenterology · doi:10.1038/ajg.2010.84 · Cited by 138 · see citing works
On communication between gut microbes and the brain
Forsythe, P., Kunze, W. A., & Bienenstock, J. (2012) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e3283572ffa · Cited by 137 · see citing works
Huang, E. Y., Leone, V. A., Devkota, S., Wang, Y., Brady, M. J., & Chang, E. B. (2013) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607113486931 · Cited by 133 · see citing works
Self-citationExpression of MUC2‐mucin in colorectal adenomas and carcinomas of different histological types
Blank, M., Klussmann, E., Krüger‐Krasagakes, S., Schmitt‐Gräff, A., Stolte, M., Bornhoeft, G., Stein, H., Xing, P., McKenzie, I. F. C., Verstijnen, C. P. H. J., et al. (1994) · International Journal of Cancer · doi:10.1002/ijc.2910590302 · Cited by 132 · see citing works
Oral glucocorticoids and their complications
Gallant, C., & Kenny, P. (1986) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(86)70018-2 · Cited by 115 · see citing works
Crinelli, R., Antonelli, A., Bianchi, M., Gentilini, L., Scaramucci, S., & Magnani, M. (2000) · Blood Cells, Molecules, and Diseases · doi:10.1006/bcmd.2000.0298 · Cited by 84 · see citing works
Nanthakumar, N. N., Young, C., Ko, J. S., Meng, D., Chen, J., Buie, T., & Walker, W. A. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00169.2004 · Cited by 79 · see citing works
Friend (1998) · Alimentary Pharmacology & Therapeutics · doi:10.1046/j.1365-2036.1998.00348.x · Cited by 75 · see citing works
Hoskins, L. C. (1993) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-199304000-00004 · Cited by 69 · see citing works
Biosynthesis of rat MUC2 in colon and its analogy with human MUC2
Tytgat, K. M. A. J., Bovelander, F. J., Opdam, F. J. M., Einerhand, A. W. C., Büller, H. A., & Dekker, J. P. (1995) · Biochemical Journal · doi:10.1042/bj3090221 · Cited by 64 · see citing works
Engels, K., Fox, S. B., Whitehouse, R. M., Gatter, K. C., & Harris, A. L. (1997) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199708)182:4 · Cited by 60 · see citing works
Meslin, J.-C., Fontaine, N., & Andrieux, C. (1999) · Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology · doi:10.1016/s1095-6433(99)00056-2 · Cited by 55 · see citing works
Sudo, N. (2006) · International Congress Series · doi:10.1016/j.ics.2005.12.019 · Cited by 46 · see citing works
van der Sluis, M., Bouma, J., Vincent, A., Velcich, A., Carraway, K. L., Büller, H. A., Einerhand, A. W. C., van Goudoever, J. B., Van Seuningen, I., & Renes, I. B. (2008) · Laboratory Investigation · doi:10.1038/labinvest.2008.28 · Cited by 44 · see citing works
Ünsal, H., Balkaya, M., Ünsal, C., Bıyık, H., Başbülbül, G., & Poyrazoğlu, E. (2008) · Digestive Diseases and Sciences · doi:10.1007/s10620-007-0089-6 · Cited by 31 · see citing works
Ulcerative Colitis: A Specific Mucin Defect?
Kim, Y. S., & Byrd, J. C. (1984) · Gastroenterology · doi:10.1016/s0016-5085(84)80086-4 · Cited by 23 · see citing works
Ramer-Tait, A., Overstreet, A.-M., Hostetter, J., Jergens, A., & Wannemuehler, M. (2012) · Inflammatory Bowel Diseases · doi:10.1097/00054725-201212001-00227 · Cited by 1 · cited 1× · see citing works
“This phylum has been shown to be intimately tied to a proinflammatory state.(10,59,60) Furthermore, these mice also exhibited increased prevalence of Clostridiales alongside a concomitant decrease in Lactobacillaceae, although these patterns were not statistically significant.”
BackgroundLiu, J., Zhang, Z., Xu, Y., et al. (2006) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Research works printed but not linked: 5
- Cerf-Bensussan, 2010, 10, 735
- Forstner, 1994, Physiol Gastrointestinal Tract, 2, 1255
- Kim, 1984, 87, 1193
- Liu, 2006, Zhonghua Yi Xue Za Zhi, 86, 2491
- Sudo, 2006, 1287, 350
Cited by
Sorted by citations
Immunological aspects of intestinal mucus and mucins
Johansson, M. E. V., & Hansson, G. C. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.88 · Cited by 1,007 · see citing works
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Elkrief, A., Derosa, L., Kroemer, G., Zitvogel, L., & Routy, B. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz206 · Cited by 246 · see citing works
Pearson-Leary, J., Zhao, C., Bittinger, K., Eacret, D., Luz, S., Vigderman, A. S., Dayanim, G., & Bhatnagar, S. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0380-x · Cited by 206 · see citing works
Involvement of the gut microbiota and barrier function in glucocorticoid-induced osteoporosis
Schepper, J. D., Collins, F., Rios-Arce, N. D., Kang, H. J., Schaefer, L., Gardinier, J. D., Raghuvanshi, R., Quinn, R. A., Britton, R., Parameswaran, N., et al. (2020) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3947 · Cited by 199 · see citing works
Schepper, J. D., Collins, F. L., Rios-Arce, N. D., Raehtz, S., Schaefer, L., Gardinier, J. D., Britton, R. A., Parameswaran, N., & McCabe, L. R. (2019) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3635 · Cited by 182 · see citing works
Wang, M., Zhu, Z., Lin, X., Li, H., Wen, C., Bao, J., & He, Z. (2021) · Arthritis Research & Therapy · doi:10.1186/s13075-021-02620-w · Cited by 52 · see citing works
- Authors
- Huang, E. Y., Inoue, T., Leone, V. A., Dalal, S., Touw, K., Wang, Y., Musch, M. W., Theriault, B., Higuchi, K., Donovan, S., Gilbert, J., & Chang, E. B.
- Affiliations
- Argonne National Laboratory (US)
- Osaka Medical and Pharmaceutical University (JP)
- University of Chicago (US)
- University of Illinois Urbana-Champaign (US)
- Corresponding author
- Chang, Eugene B.
- ORCID
- Venue
- Inflammatory Bowel Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05
- Volume
- 21
- Issue
- 5
- Pages
- 963-972
- ISSN
- 1078-0998 (ISSN-L)
- PMC
- PMC4402247
- OpenAlex
- W2043593402
- Semantic Scholar
- a8d3c7119b8371378bba0f34492b9c674b591d1b
- Cited by
- 204
- References
- 63
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 15 · 2023: 18 · 2022: 27 · 2021: 26 · 2020: 19 · 2019: 24 · 2018: 9 · 2017: 12 · 2016: 9 · 2015: 1
- FWCI
- 4.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Inflammatory Bowel Diseases (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- National Institutes of Health (UL1TR000430)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK047722, DK-47722, DK07074, R37DK047722, R01DK097268, T32DK007074, UH3DK083993, DK42086, T32 DK-07074, P30DK042086, DK097268)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, glucocorticoids
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Inflammatory Agents, Colon, Dexamethasone, DNA, Bacterial, Enzyme-Linked Immunosorbent Assay, Feces, Inflammation, Male, Mice, Inbred C57BL, Polymorphism, Restriction Fragment Length, RNA, Ribosomal, 16S, Inflammatory Bowel Diseases, Polymerase Chain Reaction, Interleukin-10, Mice, Knockout, Gastrointestinal Tract, Mice, Mucin-2
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 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
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.
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