Anxiety But Not Depression Predicts Poor Outcomes in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) have high rates of psychiatric comorbidities, but it is not clear whether those with comorbidities are at higher risk of poor outcomes. We aimed to determine whether patients with IBD who have co-existing anxiety and/or depression are more likely to have poor IBD-related outcomes compared with IBD patients without anxiety and/or depression. METHODS: This was a prospective longitudinal follow-up study in Ontario, Canada, from 2008 to 2016. Patients were asked to complete questionnaires at the time of initial assessment, including the Hospital Anxiety and Depression Scale (HADS). We selected a number of clinical variables at the time of presentation and tested their ability to predict subsequent poor IBD-related outcomes, such as IBD-related hospitalization, emergency room visits, and recurrent courses of corticosteroids over the duration of follow-up. Logistic regression was used for multivariate analysis. RESULTS: Four hundred fourteen IBD patients completed the baseline questionnaire. Among them, 125 had anxiety and/or depression at baseline. Factors that predicted poor IBD-related outcomes during longitudinal follow-up included increased severity of disease at initial presentation, prior IBD-related surgery, longer duration of follow-up, and elevated C-reactive protein at time of initial presentation. After adjustment for potential covariates, IBD patients with abnormal anxiety subscores had poor IBD-related outcomes compared with those without elevated anxiety subscores (odds ratio [OR] 3.36, 95% CI, 1.51-7.48). No difference in IBD-related outcomes were observed in those with abnormal depression subscores compared with those without elevated depression scores (OR 0.43, 95% CI, 0.14-1.32). CONCLUSIONS: Severe disease, anxiety, and previous IBD-related surgery predict poor IBD-related outcomes in patients in the future. Closer monitoring with regular follow-up may be appropriate for patients with these risk factors.

Characterization of Simultaneous Pressure Waves as Biomarkers for Colonic Motility Assessed by High-Resolution Colonic Manometry.

Simultaneous pressure waves (SPWs) in manometry recordings of the human colon have been associated with gas expulsion. Our hypothesis was that the SPW might be a critical component of most colonic motor functions, and hence might act as a biomarker for healthy colon motility. To that end, we performed high-resolution colonic manometry (HRCM), for the first time using an 84-sensor (1 cm spaced) water-perfused catheter, in 17 healthy volunteers. Intraluminal pressure patterns were recorded during baseline, proximal and rectal balloon distention, after a meal and following proximal and rectal luminal bisacodyl administration. Quantification was performed using software, based on Image J, developed during this study. Gas expulsion was always associated with SPWs, furthermore, SPWs were associated with water or balloon expulsion. SPWs were prominently emerging at the termination of proximal high amplitude propagating pressure waves (HAPWs); we termed this motor pattern HAPW-SPWs; hence, SPWs were often not a pan-colonic event. SPWs and HAPW-SPWs were observed at baseline with SPW amplitudes of 12.0 ± 8.5 mmHg and 20.2 ± 7.2 mmHg respectively. The SPW occurrence and amplitude significantly increased in response to meal, balloon distention and luminal bisacodyl, associated with 50.3% anal sphincter relaxation at baseline, which significantly increased to 59.0% after a meal, and 69.1% after bisacodyl. Often, full relaxation was achieved. The SPWs associated with gas expulsion had a significantly higher amplitude compared to SPWs without gas expulsion. SPWs could be seen to consist of clusters of high frequency pressure waves, likely associated with a cluster of fast propagating, circular muscle contractions. SPWs were occasionally observed in a highly rhythmic pattern at 1.8 ± 1.2 cycles/min. Unlike HAPWs, the SPWs did not obliterate haustral boundaries thereby explaining how gas can be expelled while solid content can remain restrained by the haustral boundaries. In conclusion, the SPW may become a biomarker for normal gas transit, the gastrocolonic reflex and extrinsic neural reflexes. The SPW assessment reveals coordination of activities in the colon, rectum and anal sphincters. SPWs may become of diagnostic value in patients with colonic dysmotility.

Ecobiotherapy Rich in Firmicutes Decreases Susceptibility to Colitis in a Humanized Gnotobiotic Mouse Model.

BACKGROUND: Alterations in the intestinal microbiota, characterized by depletion of anti-inflammatory bacteria, such as Firmicutes, in patients with ulcerative colitis (UC) have prompted interest in microbiota-modulating strategies for this condition. The aim of this study was to evaluate the role of fecal and synthetic human microbial ecosystems, low or enriched in Firmicutes, on colitis susceptibility and host immune responses. METHODS: The microbiota of selected healthy and UC human donors was characterized by culture method and 16S rRNA-based sequencing. Germ-free mice were colonized with fecal or a synthetic ecosystem enriched (healthy donors) or low (UC donors) in Firmicutes. Experimental colitis was induced using dextran sodium sulfate. Colon transcriptome and colon lamina propria cells were evaluated in mice postcolonization by RNA-seq and flow cytometry, respectively, and T helper (TH) 17 differentiation was assessed in vitro. RESULTS: Mice colonized with microbiota from patients with UC low in Firmicutes had increased sensitivity to colitis compared with mice colonized with fecal or synthetic ecosystems rich in Firmicutes. Microbiota low in Firmicutes increased expression of TH17-related genes and expansion of interleukin-17A-expressing CD4 cells in vivo. Supplementation with bacterial isolates belonging to the Firmicutes phylum abrogated the heightened TH17 responses in vitro. CONCLUSIONS: A microbiota rich in Firmicutes derived from fecal samples of a healthy human donor, or assembled synthetically, downregulated colonic inflammation and TH17 pathways in mice. The results support the use of ecobiotherapy strategies, enriched in Firmicutes, for the prevention or treatment of UC.

The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease.

Although many people are aware of the communication that occurs between the gastrointestinal (GI) tract and the central nervous system, fewer know about the ability of the central nervous system to influence the microbiota or of the microbiota's influence on the brain and behavior. Within the GI tract, the microbiota have a mutually beneficial relationship with their host that maintains normal mucosal immune function, epithelial barrier integrity, motility, and nutrient absorption. Disruption of this relationship alters GI function and disease susceptibility. Animal studies suggest that perturbations of behavior, such as stress, can change the composition of the microbiota; these changes are associated with increased vulnerability to inflammatory stimuli in the GI tract. The mechanisms that underlie these alterations are likely to involve stress-induced changes in GI physiology that alter the habitat of enteric bacteria. Furthermore, experimental perturbation of the microbiota can alter behavior, and the behavior of germ-free mice differs from that of colonized mice. Gaining a better understanding of the relationship between behavior and the microbiota could provide insight into the pathogenesis of functional and inflammatory bowel disorders.

The role of pathogenic microbes and commensal bacteria in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) reflects several pathogenetic entities including a subgroup with low-grade colonic inflammation. We propose that pathogenic bacteria act as triggers and that disturbances of commensal bacteria maintain low-grade inflammation, that in turn leads to dysfunction in the gut or brain. METHODS: Studies were performed in mice under specific pathogen-free conditions. Visceral pain was assessed by the visceromotor response and motility was assessed by in vivo fluoroscopy and in vitro by muscle contractility. Brain chemistry was assessed by in situ hybridization and behavior by standard tests. The microbiota was monitored using 16s-based RT-PCR and DGGE. RESULTS: Mice transiently infected with the nematode Trichinella spiralis exhibited changes in motility and in visceral perception that persisted for up to 6 weeks post-infection. This was accompanied by alterations in the microbiota and an upregulation of cyclooxygenase-2 which could be reversed by treatment with anti-inflammatory agents or selected probiotics. To investigate the contribution of the microbiota, we treated mice with oral antibiotics and monitored visceral perception and behavior. Antibiotic therapy produced substantial changes in the microbiota, a small increment in inflammatory activity and an increase in substance P or pain perception. Oral, but not systemic antibiotic treatment, produced changes in brain chemistry and an increase in anxiety-like behavior. CONCLUSION: These studies provide proof of concept that pathogenic microbes can induce persistent gut dysfunction and that changes in microbial composition of the gut can maintain gut dysfunction as well as induce behavioral changes reminiscent of the psychiatric comorbidity that occurs in up to 60% of irritable bowel syndrome patients.

13C urea breath test for (Helicobacter pylori): determination of the optimal cut-off point in a Canadian community population.

AIM: To determine the test characteristics and the optimal cut-off point for the (13)C urea breath test ((13)C UBT) in a Canadian community laboratory setting. METHODS: Of 2232 patients (mean age +/- SD: 51+/-21 years, 56% female) who completed a (13)C UBT, 1209 were tested to evaluate the primary diagnosis of (Helicobacter pylori) infection and 1023 were tested for confirmation of eradication following treatment. Cluster analysis was performed on the (13)C UBT data to determine the optimal cut-off point and the risk of false-positive and false-negative results. Additionally, 176 patients underwent endoscopic biopsy to allow validation of the sensitivity and specificity of the (13)C UBT against histology and microbiology using the calculated cut-off point. RESULTS: The calculated cut-off points were 3.09 delta/1000 for the whole study population (n=2232), 3.09 delta/1000 for the diagnosis group (n=1209) and 2.88 delta/1000 for the post-treatment group (n=1023). When replacing the calculated cut-off points by a practical cut-off point of 3.0 delta/1000, the risk of false-positive and false-negative results was lower than 2.3%. The (13)C UBT showed 100% sensitivity and 98.5% specificity compared with histology and microbiology (n=176) for the diagnosis of active (H pylori) infection. CONCLUSIONS: The (13)C UBT is an accurate, noninvasive test for the diagnosis of (H pylori) infection and for confirmation of cure after eradication therapy. The present study confirms the validity of a cut-off point of 3.0 delta/1000 for the (13)C UBT when used in a large Canadian community population according to a standard protocol.

13C urea breath test for (Helicobacter pylori): evaluation of 10-minute breath collection.

AIM: To determine whether a shortened (13)C urea breath test ((13)C UBT) (breath collection time of 10 min) is as reliable as the standard assay (30 min). METHODS: Two hundred ninety-seven patients (mean +/- SD: 53+/-16 years, 57% female) completed a (13)C UBT. Breath samples were obtained at baseline and at 5 min intervals up to 30 min. Sixty-seven patients also underwent endoscopic biopsy. Cluster analysis was performed on the (13)C UBT data to determine the optimal cut-off point at each time interval. Sensitivity and specificity of the (13)C UBT at all intervals compared with histology and culture and against the standard 30 min interval were determined. RESULTS: The calculated optimal cut-off points for each time interval (T), expressed as delta over baseline (delta/1000), were 3.29 delta/1000 at T(5), 3.15 delta/1000 at T(10), 3.42 delta/1000 at T(15), 3.17 delta/1000 at T(20), 2.99 delta/1000 at T(25) and 2.82 delta/1000 at T(30). Except at T(5), the risk of false-positive and false-negative test results at each time interval was lower than 2.3% using these cut-off points. When replacing the cut-off points with 3.0 delta/1000, the risk of error was still lower than 2.3%. The test at T(10) showed 98.6% sensitivity and 98.6% specificity compared with T(30). T(10) and T(30) showed 100% sensitivity and 96% specificity compared with histology and culture. CONCLUSIONS: The (13)C UBT is an accurate, noninvasive test, even when the breath sample interval is reduced to 10 min. The present study confirms the validity of a cut-off point of 3.0 delta/1000 for the 10 min and 30 min (13)C UBT.