Circadian Rhythm Disruption Aggravates DSS-Induced Colitis in Mice with Fecal Calprotectin as a Marker of Colitis Severity

Amara, Joseph; Saliba, Youakim; Hajal, Joelle; Smayra, Viviane; Bakhos, Jules-Joël; Sayegh, Raymond; Farès, Nassim

doi:10.1007/s10620-019-05675-7

Cited by 24 publications

(21 citation statements)

References 67 publications

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“…78 Studies inducing chronodisruption by constant light exposure or by exposing mice to weekly circadian shifts showed an increase in permeability and a higher susceptibility to inflammation. 43,80,81 Kyoko et al showed 24h rhythmicity in Ocln and Cldn1 mRNA expression in the large intestine that was under control of the clock components ARNTL and CLOCK. 10 This is not in accordance with results, we a rhythm in Ocln, but not Cldn1 and Tjp1 mRNA expression in the distal colonic mucosa in control mice.…”

Section: Discussionmentioning

confidence: 99%

Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice

et al. 2021

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Aim: Chronodisruption desynchronizes peripheral clocks and leads to metabolic diseases. Feeding cues are important synchronizers of peripheral clocks and influence rhythmic oscillations in intestinal microbiota and their metabolites. We investigated whether chronic jetlag, mimicking frequent time zone travelling, affected the diurnal fluctuations in faecal short-chain fatty acid (SCFA) levels, that feed back to the gut clock to regulate rhythmicity in gut function. Methods: Rhythms in faecal SCFAs levels and in the expression of clock genes and epithelial markers were measured in the colonic mucosa of control and jetlagged mice. The entraining effect of SCFAs on the rhythm in clock gene mRNA expression was studied in primary colonic crypts. The role of the circadian clock in epithelial marker expression was studied in Arntl −/− mice. Results: Chronic jetlag increased body weight gain and abolished the day/night food intake pattern which resulted in a phase-delay in the rhythm of faecal SCFAs that paralleled the shift in the expression of mucosal clock genes. This effect was mimicked by stimulation of primary colonic crypts from control mice with SCFAs. Jetlag abolished the rhythm in Tnfα, proglucagon and ghrelin expression but not in the expression of tight junction markers. Only a dampening in plasma glucagon-like peptide-1 but not in ghrelin levels was observed. Rhythms in ghrelin but not proglucagon mRNA expression were abolished in Arntl −/− mice. Conclusion:The altered food intake pattern during chronodisruption corresponds with the changes in rhythmicity of SCFA levels that entrain clock genes to affect rhythms in mRNA expression of gut epithelial markers.

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Section: Discussionmentioning

confidence: 99%

Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice

et al. 2021

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“…In different models including colitis and ischemia and reperfusion (I/R), PAR-2 transcription was upregulated in mouse, rodent, and horse models (21)(22)(23). Other markers of intestinal inflammation are calprotectin (CALP) and pro-inflammatory cytokines, which have been shown to be upregulated in IBD models (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Non-invasive Assessment of Fecal Stress Biomarkers in Hunting Dogs During Exercise and at Rest

et al. 2020

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Intense exercise causes to organisms to have oxidative stress and inflammation at the gastrointestinal (GI) level. The reduction in intestinal blood flow and the exercise-linked thermal damage to the intestinal mucosa can cause intestinal barrier disruption, followed by an inflammatory response. Furthermore, the adaptation to exercise may affect the gut microbiota and the metabolome of the biofluids. The aim of the present research was to evaluate the presence of a GI derangement in hunting dogs through a non-invasive sampling as a consequence of a period of intense exercise in comparison with samples collected at rest. The study included nine dogs that underwent the same training regime for hunting wild boar. In order to counterbalance physiological variations, multiple-day replicates were collected and pooled at each experimental point for each dog. The samples were collected immediately at rest before the training (T0), after 60 days of training (T1), after 60 days of hunting wild boar (T2), and finally, at 60 days of rest after hunting (T3). A number of potential stress markers were evaluated: fecal cortisol metabolites (FCMs) as a major indicator of altered physiological states, immunoglobulin A (IgA) as an indicator of intestinal immune protection, and total antioxidant activity [total antioxidant capacity (TAC)]. Since stool samples contain exfoliated cells, we investigated also the presence of some transcripts involved in GI permeability [occludin (OCLN), protease-activated receptor-2 (PAR-2)] and in the inflammatory mechanism [interleukin (IL)-8, IL-6, IL-1b, tumor necrosis factor alpha (TNFα), calprotectin (CALP), heme oxygenase-1 (HO-1)]. Finally, the metabolome and the microbiota profiles were analyzed. No variation in FCM and IgA content and no differences in OCLN and CALP gene expression between rest and training were observed. On the contrary, an increase in PAR-2 and HO-1 transcripts, a reduction in total antioxidant activity, and a different profile of microbiota and metabolomics data were observed. Collectively, the data in the present study indicated that physical exercise in our model could be considered a mild stressor stimulus.

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“…The effect of M. vaccae NCTC 11659 is absent in mice exposed to chronic disruption of rhythms. Nevertheless, immunization with M. vaccae NCTC 11659 prevented the effects of circadian misalignment on the alpha diversity of the gut microbiome and brainstem serotonergic systems and therefore could conceivably prevent some negative outcomes of circadian misalignment not measured here, such as colitis (Preuss et al, 2008;Liu et al, 2017;Amara et al, 2019) and affective behavioral responses (Daut et al, 2019). repositories (http://massive.ucsd.edu/MSV000082649/ and (http://massive.ucsd.edu/), Dataset Identifiers: MSV000082649 (plasma) and MSV000082650 (fecal).…”

Section: Resultsmentioning

confidence: 90%

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a “Two Hit” Stressor Model

et al. 2021

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Previous studies demonstrate that Mycobacterium vaccae NCTC 11659 (M. vaccae), a soil-derived bacterium with anti-inflammatory and immunoregulatory properties, is a potentially useful countermeasure against negative outcomes to stressors. Here we used male C57BL/6NCrl mice to determine if repeated immunization with M. vaccae is an effective countermeasure in a “two hit” stress exposure model of chronic disruption of rhythms (CDR) followed by acute social defeat (SD). On day –28, mice received implants of biotelemetric recording devices to monitor 24-h rhythms of locomotor activity. Mice were subsequently treated with a heat-killed preparation of M. vaccae (0.1 mg, administered subcutaneously on days –21, –14, –7, and 27) or borate-buffered saline vehicle. Mice were then exposed to 8 consecutive weeks of either stable normal 12:12 h light:dark (LD) conditions or CDR, consisting of 12-h reversals of the LD cycle every 7 days (days 0–56). Finally, mice were exposed to either a 10-min SD or a home cage control condition on day 54. All mice were exposed to object location memory testing 24 h following SD. The gut microbiome and metabolome were assessed in fecal samples collected on days –1, 48, and 62 using 16S rRNA gene sequence and LC-MS/MS spectral data, respectively; the plasma metabolome was additionally measured on day 64. Among mice exposed to normal LD conditions, immunization with M. vaccae induced a shift toward a more proactive behavioral coping response to SD as measured by increases in scouting and avoiding an approaching male CD-1 aggressor, and decreases in submissive upright defensive postures. In the object location memory test, exposure to SD increased cognitive function in CDR mice previously immunized with M. vaccae. Immunization with M. vaccae stabilized the gut microbiome, attenuating CDR-induced reductions in alpha diversity and decreasing within-group measures of beta diversity. Immunization with M. vaccae also increased the relative abundance of 1-heptadecanoyl-sn-glycero-3-phosphocholine, a lysophospholipid, in plasma. Together, these data support the hypothesis that immunization with M. vaccae stabilizes the gut microbiome, induces a shift toward a more proactive response to stress exposure, and promotes stress resilience.

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Circadian Rhythm Disruption Aggravates DSS-Induced Colitis in Mice with Fecal Calprotectin as a Marker of Colitis Severity

Cited by 24 publications

References 67 publications

Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice

Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice

Non-invasive Assessment of Fecal Stress Biomarkers in Hunting Dogs During Exercise and at Rest

Effects of Immunization With the Soil-Derived Bacterium Mycobacterium vaccae on Stress Coping Behaviors and Cognitive Performance in a “Two Hit” Stressor Model

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