Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease

Craven, Melanie; Egan, Charlotte E.; Dowd, Scot E.; McDonough, Sean P.; Dogan, Belgin; Denkers, Eric; Bowman, Dwight D.; Scherl, Ellen; Simpson, Kenneth W.

doi:10.1371/journal.pone.0041594

Cited by 184 publications

(163 citation statements)

References 58 publications

(93 reference statements)

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“…Several studies have shown a link between diversity and inflammation, although there is debate as to which is the causative agent. 21,29,36 In our study, the decrease in diversity was evident two weeks post-surgery, but significant markers of inflammation did not occur until six weeks post-SBR. Thus, it is our hypothesis that the colonic microbiota is negatively impacted by the altered luminal environment following the surgical resection, resulting in a decrease in diversity, which initiates a pro-inflammatory response in the colon.…”

Section: Methodscontrasting

confidence: 42%

Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

et al. 2013

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IntroductionShort bowel syndrome (SBS) is the clinical state of malabsorption and malnutrition that occurs following small bowel resection (SBR). 1 Surgical resection of the small bowel may be required for the treatment of a range of conditions including congenital bowel abnormalities and necrotising enterocolitis in children and Crohn disease, trauma and malignancy in adults. Although the underlying reason for SBR between adults and children may differ, the clinical manifestations and consequences of SBS are similar. The symptoms of SBS reflect the loss of absorptive surface area and functional disturbance of the Background and objectives: Following small bowel resection (sBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (sBs) including malabsorption, mucosal inflammation and bacterial overgrowth. however, the impact of sBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following sBR and to assess the impact of sBR on mucosal inflammation in the colon.Results: analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-sBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery.Methods: Female (4-week old) piglets (5-6/group) received a 75% sBR, a transection (sham) or no surgery. compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two-and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-pcR and the number of macrophages and percentage inducible nitric oxide synthase (iNOs) staining in the colonic epithelium were quantified by immunohistochemistry.Conclusions: sBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that sBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.

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Section: Methodscontrasting

confidence: 42%

Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

et al. 2013

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“…Interestingly, T. gondii exposure is a well-documented risk factor for schizophrenia [83,84], and as a gut pathogen is a tool used in experimental models to produce an inflammatory state in the GI tract. Thus not surprisingly, T. gondii infection can drive the dysbiosis of resident microbial communities and bring about a state of increased GI permeability [85][86][87][88]. In our studies of clinical samples, we found correlations between levels of T. gondii IgG with food antigen IgG in people with a recent onset of schizophrenia, which were not present in control groups [13].…”

Section: Epithelial and Endothelial Barrier Integritiesmentioning

confidence: 60%

Gastroenterology issues in schizophrenia: Why the gut matters

Severance

2016

Eur. psychiatr.

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Genetic and environmental studies implicate immune pathologies in schizophrenia. The body's largest immune organ is the gastrointestinal (GI) tract. Historical associations of GI conditions with mental illnesses predate the introduction of antipsychotics. Current studies of antipsychoticnaïve patients support that gut dysfunction may be inherent to the schizophrenia disease process. Risk factors for schizophrenia (inflammation, food intolerances, Toxoplasma gondii exposure, cellular barrier defects) are part of biological pathways that intersect those operant in the gut. Central to GI function is a homeostatic microbial community that early reports show is disrupted in schizophrenia. Bioactive and toxic products derived from digestion and microbial dysbiosis activate adaptive and innate immunity. Complement C1q, a brain-active systemic immune component, interacts with gut-related schizophrenia risk factors in clinical and experimental animal models. With accumulating evidence supporting newly discovered gut-brain physiological pathways, treatments to ameliorate brain symptoms of schizophrenia should be supplemented with therapies to correct GI dysfunction.

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“…The unfavorable combination of inflammation and host genetics promotes development of gut dysbiosis and reduced diversity in the microbial community (Craven et al. 2012; Machiels et al. 2014).…”

Section: Discussionmentioning

confidence: 99%

Mutual reinforcement of pathophysiological host‐microbe interactions in intestinal stasis models

Touw

Ringus

Hubert

et al. 2017

Physiological Reports

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Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models – an opioid‐induced constipation model in mice, and a humanized mouse model where germ‐free mice were colonized with stool from a patient with constipation‐predominant irritable bowel syndrome (IBS‐C) in humans. We examined the impact of pharmacologically (loperamide)‐induced constipation (PIC) and IBS‐C on the structural and functional profile of the gut microbiota. Germ‐free (GF) mice were colonized with microbiota from PIC donor mice and IBS‐C patients to determine how the microbiota affects the host. PIC and IBS‐C promoted changes in the gut microbiota, characterized by increased relative abundance of Bacteroides ovatus and Parabacteroides distasonis in both models. PIC mice exhibited decreased luminal concentrations of butyrate in the cecum and altered metabolic profiles of the gut microbiota. Colonization of GF mice with PIC‐associated mice cecal or human IBS‐C fecal microbiota significantly increased GI transit time when compared to control microbiota recipients. IBS‐C‐associated gut microbiota also impacted colonic contractile properties. Our findings support the concept that constipation is characterized by disease‐associated steady states caused by reinforcement of pathophysiological factors in host‐microbe interactions.

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Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease

Cited by 184 publications

References 58 publications

Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

Gastroenterology issues in schizophrenia: Why the gut matters

Mutual reinforcement of pathophysiological host‐microbe interactions in intestinal stasis models

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