Post-traumatic stress disorder symptoms are frequent among inflammatory bowel disease patients of South Asian descent-A case-control study.

BACKGROUND: Post-traumatic stress (PTS) is the psycho-physiological response to a traumatic or life-threatening event and is implicated in inflammatory bowel disease (IBD). IBD-PTS is present in up to 30% of white, non-Hispanic patients. The rates of IBD in Asian populations are expanding, making the exploration of IBD-PTS in this population imperative. METHODS: Adult patients of South/Southeast (S/SE) Asian decent with IBD for more than 6 months were recruited online via social media and patient-support groups. Participants completed the post-traumatic stress disorder (PTSD) Checklist-5 (PCL-5), the United States National Institutes of Health's Patient-Reported Outcomes Measurement Information System (NIH-PROMIS) -43 profile and demographics. S/SE Asian participants were age and sex matched (1:2) with randomly selected white, non-Hispanic controls. Statistical analyses evaluated differences in IBD-PTS symptoms between groups, the relationship between disease severity and health-related quality of life (HRQoL) and predictors of IBD-PTS severity. RESULTS: Forty-seven per cent of the 51 S/SE Asian participants met the diagnostic cut-off for PTSD on the PCL-5 compared to 13.6% of 110 IBD controls. The mean global score on the PCL-5 was three times higher in S/SE Asians. Patients of S/SE Asian decent were over five times more likely to have PTSD due to their IBD experiences than controls, nearly doubling when controlling for disease activity. More severe IBD-PTS was present in S/SE Asian patients with active disease and those with extraintestinal manifestations. Higher global levels of IBD-PTS were associated with poorer HRQoL in S/SE Asians where increased hyperarousal from IBD-PTS predicted more sleep disturbance. CONCLUSIONS: S/SE Asian patients are five times more likely to experience IBD-PTS than their white, non-Hispanic counterparts. Several cultural factors lead to IBD-PTS in S/SE Asian patients that must be considered by IBD providers. Preventing, screening for and treating IBD-PTS in this population appears warranted.

Comparison of gut microbiome composition in colonic biopsies, endoscopically-collected and at-home-collected stool samples.

Aim: The goal of this study is to compare microbiome composition in three different sample types in women, namely stool brought from home vs. solid stool samples obtained at the time of an unprepped sigmoidoscopy vs. biopsies of the colonic mucosa at the time of an unprepped sigmoidoscopy, using alpha- and beta-diversity metrics following bacterial 16S rRNA sequencing. The findings may have relevance to health and disease states in which bacterial metabolism has a significant impact on molecules/metabolites that are recirculated between the gut lumen and mucosa and systemic circulation, such as estrogens (as in breast cancer) or bile acids. Methods: Concomitant at-home-collected stool, endoscopically-collected stool, and colonic biopsy samples were collected from 48 subjects (24 breast cancer, 24 control.) After 16S rRNA sequencing, an amplicon sequence variant (ASV) based approach was used to analyze the data. Alpha diversity metrics (Chao1, Pielou's Evenness, Faith PD, Shannon, and Simpson) and beta diversity metrics (Bray-Curtis, Weighted and Unweighted Unifrac) were calculated. LEfSe was used to analyze differences in the abundance of various taxa between sample types. Results: Alpha and beta diversity metrics were significantly different between the three sample types. Biopsy samples were different than stool samples in all metrics. The highest variation in microbiome diversity was noted in the colonic biopsy samples. At-home and endoscopically-collected stool showed more similarities in count-based and weighted beta diversity metrics. There were significant differences in rare taxa and phylogenetically-diverse taxa between the two types of stool samples. Generally, there were higher levels of Proteobacteria in biopsy samples, with significantly more Actinobacteria and Firmicutes in stool (all p < 0.001, q-value < 0.05). Overall, there was a significantly higher relative abundance of Lachnospiraceae and Ruminococcaceae in stool samples (at-home collected and endoscopically-collected) and higher abundances of Tisserellaceae in biopsy samples (all p < 0.001, q-value < 0.05). Conclusion: Our data shows that different sampling methods can impact results when looking at the composition of the gut microbiome using ASV-based approaches.

Hospitalization Experiences and Post-traumatic Stress in Inflammatory Bowel Disease: Opportunities for Change.

INTRODUCTION: Medical trauma related to IBD (IBD-PTS) affects approximately 25% of patients and is associated with poor outcomes. Prior studies identify common hospitalization experiences as potentially traumatic but have not measured risk relationships for the development of IBD-PTS. We aim to investigate what aspects of hospitalizations may increase the chance of medical trauma and IBD-PTS development. METHODS: Adult patients with IBD enrolled in the IBD Partners database were recruited. Study specific questionnaires included PTSD checklist, 5th edition (PCL-5), patient experience questionnaire, and items about the patient's most stressful hospitalization and nonhospital sources of medical trauma. Established criteria for the PCL-5 identified significant IBD-PTS symptoms (re-experiencing, avoidance, mood change, hyperarousal, global diagnosis). Select disease and treatment information was obtained from the main IBD Partners dataset. Univariate and multivariate statistics evaluated the relationships between hospitalization data and IBD-PTS. RESULTS: There were 639 participants with at least 1 hospitalization for IBD included. Approximately two-thirds had Crohn's disease; most were White, non-Hispanic, female, middle-aged, and reported their IBD as being in remission. Forty percent of patients stated a hospitalization was a source of IBD-PTS. Frequent anxiety while hospitalized increased the odds of IBD-PTS 2 to 4 times; similar relationships existed for pain/pain control. Higher quality communication, information, and listening skills reduced the odds of IBD-PTS, albeit marginally. CONCLUSIONS: Patients with IBD consistently cite hospitalizations as potential sources of medical trauma. Poorly managed anxiety and pain demonstrate the greatest chance for IBD-PTS development. Gender and racial/ethnic differences emerged for these risks. Positive interactions with the medical team may help mitigate in-hospital IBD-PTS development.

This study finds IBD patients with the poorest hospital experiences and those with poor pain and anxiety control are at the highest risk of developing post-traumatic stress disorder symptoms due to medical trauma. Medical staff behavior is an important consideration.

Posttraumatic Stress in Patients With Inflammatory Bowel Disease: Prevalence and Relationships to Patient-Reported Outcomes.

BACKGROUND: Patients with chronic illness are at increased risk for traumatic stress because of medical trauma. Initial studies of posttraumatic stress (PTS) in patients with inflammatory bowel disease (IBD) have found that approximately one-third of patients may experience significant PTS symptoms including flashbacks, nightmares, hypervigilance, disrupted sleep, and low mood. We aim to better characterize PTS in IBD and its relationship with patient outcomes in a large cohort of patients with IBD. METHODS: Adult patients registered with the Crohn's & Colitis Foundation/University of North Carolina IBD Partners database were invited to complete a supplementary survey between February and July 2020. The Post Traumatic Stress Disorder Checklist-5th edition was administered as a supplemental survey. Additional data from IBD Partners included disease severity, surgery and hospital history, demographics, and health care utilization. RESULTS: A total of 797 patients participated (452 with Crohn disease, 345 with ulcerative colitis). No impacts on response patterns because of the COVID-19 pandemic were found. Although 5.6% of the sample reported an existing PTS diagnosis because of IBD experiences, 9.6% of participants met the full IBD-related PTS diagnostic criteria per the Post Traumatic Stress Disorder Checklist-5th edition. Female patients, younger patients, those with less educational attainment, non-White patients, and Hispanic patients reported higher levels of PTS symptoms. Patients with higher PTS symptoms were more likely to have been hospitalized, have had surgery, have more severe symptoms, and not be in remission. Increased PTS was also associated with increased anxiety, depression, pain interference, fatigue, and health care utilization. CONCLUSIONS: The present findings support prior research that approximately one-quarter to one-third of patients with IBD report significant symptoms of PTS directly from their disease experiences, and certain demographic groups are at higher risk. In addition, PTS is associated with several IBD outcomes. Patients with higher PTS symptoms are less likely to be in remission and may utilize more outpatient gastrointestinal services. Intervention trials to mitigate PTS symptoms in patients with IBD are warranted.

Patient Perspectives on Medical Trauma Related to Inflammatory Bowel Disease.

Post-traumatic stress symptoms (PTSS) in response to medical trauma are understudied in inflammatory bowel disease (IBD). Two studies identify surgery, hospitalizations, and disease severity as risk factors. We aimed to document IBD-related patient experiences and how these relate to PTSS via a qualitative study. Adult patients with confirmed IBD recruited from two gastroenterology clinics underwent a semi-structured interview with a psychologist and completed the Post Traumatic Stress Disorder Symptom Scale for DSM5 (PSSI-5). Interviews were analyzed using an interpretive phenomenological approach. Themes and subthemes with representative quotations were documented based on thematic saturation. 16 participants, five met PSSI-5 criteria for PTSD. Five themes emerged: disease uncertainty, information exchange/quality, medical procedures, surgery, and coping. Patients with IBD may experience medical PTSS from several sources. Information, communication, and trust in clinicians is vital but may be sub-optimal. Both adaptive and maladaptive coping strategies are used to mitigate PTSS.

IL-6 Inhibition in Critically Ill COVID-19 Patients Is Associated With Increased Secondary Infections.

Background: Anti-inflammatory therapies such as IL-6 inhibition have been proposed for COVID-19 in a vacuum of evidence-based treatment. However, abrogating the inflammatory response in infectious diseases may impair a desired host response and pre-dispose to secondary infections. Methods: We retrospectively reviewed the medical record of critically ill COVID-19 patients during an 8-week span and compared the prevalence of secondary infection and outcomes in patients who did and did not receive tocilizumab. Additionally, we included representative histopathologic post-mortem findings from several COVID-19 cases that underwent autopsy at our institution. Results: One hundred eleven patients were identified, of which 54 had received tocilizumab while 57 had not. Receiving tocilizumab was associated with a higher risk of secondary bacterial (48.1 vs. 28.1%; p = 0.029 and fungal (5.6 vs. 0%; p = 0.112) infections. Consistent with higher number of infections, patients who received tocilizumab had higher mortality (35.2 vs. 19.3%; p = 0.020). Seven cases underwent autopsy. In three cases who received tocilizumab, there was evidence of pneumonia on pathology. Of the four cases that had not been given tocilizumab, two showed evidence of aspiration pneumonia and two exhibited diffuse alveolar damage. Conclusions: Experimental therapies are currently being applied to COVID-19 outside of clinical trials. Anti-inflammatory therapies such as anti-IL-6 therapy have the potential to impair viral clearance, pre-dispose to secondary infection, and cause harm. We seek to raise physician awareness of these issues and highlight the need to better understand the immune response in COVID-19.

IL6 inhibition in critically ill COVID-19 patients is associated with increased secondary infections.

BACKGROUND: Anti-inflammatory therapies such as IL-6 inhibition have been proposed for COVID-19 in a vacuum of evidence-based treatment. However, abrogating the inflammatory response in infectious diseases may impair a desired host response and predispose to secondary infections. METHODS: We retrospectively reviewed the medical record of critically ill COVID-19 patients during an 8-week span and compared the prevalence of secondary infection and outcomes in patients who did and did not receive tocilizumab. Additionally, we included representative histopathologic post-mortem findings from several COVID-19 cases that underwent autopsy at our institution. RESULTS: 111 patients were identified, of which 54 had received tocilizumab while 57 had not. Receiving tocilizumab was associated with a higher risk of secondary bacterial (48.1% vs. 28.1%, p=0.029 and fungal (5.6% vs. 0%, p=0.112) infections. Consistent with higher number of infections, patients who received tocilizumab had higher mortality (35.2% vs. 19.3%, p=0.020). Seven cases underwent autopsy. In 3 cases who received tocilizumab, there was evidence of pneumonia on pathology. Of the 4 cases that had not been given tocilizumab, 2 showed evidence of aspiration pneumonia and 2 exhibited diffuse alveolar damage. CONCLUSIONS: Experimental therapies are currently being applied to COVID-19 outside of clinical trials. Anti-inflammatory therapies such as anti-IL-6 therapy have the potential to impair viral clearance, predispose to secondary infection, and cause harm. We seek to raise physician awareness of these issues and highlight the need to better understand the immune response in COVID-19.

Diet Therapy for Inflammatory Bowel Diseases: A Call to the Dining Table.

There is vigorous interest among patients, caregivers, clinicians, and scientists to identify useful dietary interventions for inflammatory bowel diseases (IBD). Through the Cochrane Collaboration, we recently performed a systematic review and meta-analysis of dietary interventions for the induction or maintenance of remission in Crohn's disease (CD) and ulcerative colitis (UC) to assess the latest state of research. The current quality of evidence was formally graded to be low or very low for various methodological reasons, such as small sample sizes, heterogeneity among studies, and incomplete reporting. There are nonetheless emerging observational studies that progressively advance our knowledge and provide hope for a role of diet among traditional therapies to improve inflammation and symptoms. Further investments and concerted efforts in research are needed to significantly move the needle in identifying effective dietary therapies for IBD.

Development of collagenous colitis in inflammatory bowel disease: two case reports and a review of the literature.

The occurrence of collagenous colitis (CC) in patients with pre-existing inflammatory bowel diseases (IBD) is rare, with only seven cases reported in the past. Herein, we report two IBD cases who developed CC after successful treatment of their IBD with two different tumor necrosis factor (TNF)-α inhibitors, which have been previously reported to successfully treat refractory CC. This report highlights the need to do random biopsies of the colon for CC diagnosis in IBD patients with symptoms of diarrhea after complete mucosal healing. The report also reviews plausible mechanisms as to how CC may develop, including the role of multiple medications.

Food-related quality of life in patients with inflammatory bowel disease and irritable bowel syndrome.

BACKGROUND: Food-related quality of life (FRQoL) evaluates the impact of diet, eating behaviors, and food-related anxiety on a person's quality of life. This is the first study to evaluate FRQoL in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), two illnesses where food and diet are of importance. METHODS: One hundred seventy-five participants (80 IBS, 95 IBD) participated in the study by completing measures evaluating FRQoL, psychological distress, and health-related quality of life. Primary analyses evaluated differences in FRQoL between IBD and IBS patients. Secondary analyses compared differences based on remission status, dietary use, and dietary consultation, as well as evaluated potential predictors of FRQoL. RESULTS: IBD patients in remission report the highest FRQoL (IBD-remission: 91.2 (26.5) vs. IBD-active: 67.7 (19.6) and IBS-active: 67.6 (18.3), p < .001). Using more dietary treatments is associated with decreased FRQoL for IBS (r = - 0.23, p < .05) and IBD patients (r = - 0.31, p < .01). IBS patients are more likely to use dietary treatments than IBD (IBS = 81% vs. IBD = 64%, p < .01), with self-directed diets being the most commonly used approach. Symptom severity is the strongest predictor of FRQoL in both groups (IBD: R2 = .27, p < .01; IBS: R2 = .23, p < .001). CONCLUSION: FRQoL is a unique construct for IBD and IBS patients that can be influenced by several clinical and dietary factors, including number of diets and type of diet used, depending on the diagnosis. Thus, FRQoL should be considered when working with both IBD and IBS patients.

Collagenous colitis development occurs after long standing mucosal healing in IBD with TNF-α inhibitors, and could be due to exaggerated healing response from excess TNF-α inhibition.

Collagenous colitis is a relatively rare disorder affecting mainly middle-aged women where they present with chronic non-bloody diarrhea. Both with lymphocytic colitis they compose microscopic colitis. The exact cause of collagenous colitis is still unknown however; many potential pathophysiologic mechanisms have been proposed but no convincing mechanism has been identified. Collagenous colitis has been linked to medications mainly NSAIDs, SSRIs, and PPIs. It is also believed that collagenous colitis is autoimmune disease and there are weak believe it could have some genetic inheritance. We reported before two cases of collagenous colitis developed in patients with Crohn's disease and ulcerative colitis while they were in complete mucosal remission after being treated with tumor necrosis factors-α inhibitors. In this article we will try to explain how collagenous colitis can develop in patients with inflammatory bowel disease especially those on tumor necrosis factors-α inhibitors.

A descriptive analysis of real-world treatment patterns of innovator (Remicade®) and biosimilar infliximab in an infliximab-naïve Turkish population.

PURPOSE: Biosimilar IFX (CT-P13) received marketing approval in Turkey for treatment of rheumatologic diseases, including ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Population data on real-world treatment patterns of CT-P13 following marketing approval in European countries are largely unreported. This study examined the prescribing and medication utilization patterns of innovator infliximab (IFX) and CT-P13 in Turkey for patients with RA or IBD naïve to either IFX. MATERIALS AND METHODS: Adult patients with ≥1 diagnosis claim for RA or IBD and ≥1 claim for IFX or CT-P13 were identified in the Turkish Ministry of Health database during the following identification periods: 1 Oct 2014-30 May 2015 (RA) and 1 Oct 2014-31 Dec 2015 (IBD). Continuous medical and pharmacy coverage for ≥12 months before and after the date of the first dose (index) IFX or CT-P13 was also required. Separate analyses were done for each population. RESULTS: Seven hundred and seventy nine adult RA and 581 IBD patients met the selection criteria. The majority of RA (74%; n=575) and IBD patients (87%; n=504) were initiated on IFX. The average study observation period was 16 months for the RA and 12 months for the IBD population. Over the observation periods, discontinuation among RA patients occurred in 42% of IFX and 63% of CT-P13 while discontinuation in the IBD cohort occurred in 38% of IFX; and 62% of CT-P13. CONCLUSION: In this population-based study, more IFX-naïve RA and IBD patients were initially treated with IFX than CT-P13. Discontinuation and switching were observed more often and earlier among patients treated with CT-P13 regardless of disease state. Further studies are needed to understand the reasons for these observed differences.

Inhalational exposure to particulate matter air pollution alters the composition of the gut microbiome.

Recent studies suggest an association between particulate matter (PM) air pollution and gastrointestinal (GI) disease. In addition to direct deposition, PM can be indirectly deposited in oropharynx via mucociliary clearance and upon swallowing of saliva and mucus. Within the GI tract, PM may alter the GI epithelium and gut microbiome. Our goal was to determine the effect of PM on gut microbiota in a murine model of PM exposure via inhalation. C57BL/6 mice were exposed via inhalation to either concentrated ambient particles or filtered air for 8-h per day, 5-days a week, for a total of 3-weeks. At exposure's end, GI tract tissues and feces were harvested, and gut microbiota was analyzed. Alpha-diversity was modestly altered with increased richness in PM-exposed mice compared to air-exposed mice in some parts of the GI tract. Most importantly, PM-induced alterations in the microbiota were very apparent in beta-diversity comparisons throughout the GI tract and appeared to increase from the proximal to distal parts. Changes in some genera suggest that distinct bacteria may have the capacity to bloom with PM exposure. Exposure to PM alters the microbiota throughout the GI tract which maybe a potential mechanism that explains PM induced inflammation in the GI tract.

A compartmentalized type I interferon response in the gut during chronic HIV-1 infection is associated with immunopathogenesis.

OBJECTIVE(S): Type I interferon (IFN-I) responses confer both protective and pathogenic effects in persistent virus infections. IFN-I diversity, stage of infection and tissue compartment may account for this dichotomy. The gut is a major site of early HIV-1 replication and microbial translocation, but the nature of the IFN-I response in this compartment remains unclear. DESIGN: Samples were obtained from two IRB-approved cross-sectional studies. The first study included individuals with chronic, untreated HIV-1 infection (n = 24) and age/sex-balanced uninfected controls (n = 14). The second study included antiretroviral-treated, HIV-1-infected individuals (n = 15) and uninfected controls (n = 15). METHODS: The expression of 12 IFNα subtypes, IFNß and antiviral IFN-stimulated genes (ISGs) were quantified in peripheral blood mononuclear cells (PBMCs) and colon biopsies using real-time PCR and next-generation sequencing. In untreated HIV-1-infected individuals, associations between IFN-I responses and gut HIV-1 RNA levels as well as previously established measures of colonic and systemic immunological indices were determined. RESULTS: IFNα1, IFNα2, IFNα4, IFNα5 and IFNα8 were upregulated in PBMCs during untreated chronic HIV-1 infection, but IFNß was undetectable. By contrast, IFNß was upregulated and all IFNα subtypes were downregulated in gut tissue. Gut ISG levels positively correlated with gut HIV-1 RNA and immune activation, microbial translocation and inflammation markers. Gut IFN-I responses were not significantly different between HIV-1-infected individuals on antiretroviral treatment and uninfected controls. CONCLUSION: The IFN-I response is compartmentalized during chronic untreated HIV-1 infection, with IFNß being more predominant in the gut. Gut IFN-I responses are associated with immunopathogenesis, and viral replication is likely a major driver of this response.

Diet as a Therapeutic Option for Adult Inflammatory Bowel Disease.

There are many mechanisms to explain how food may drive and ameliorate inflammation. Although there are no consistent macronutrient associations inflammatory bowel disease (IBD) development, many exclusion diets have been described: IgG-4 guided exclusion diet; semivegetarian diet; low-fat, fiber-limited exclusion diet; Paleolithic diet; Maker's diet; vegan diet; Life without Bread diet; exclusive enteral nutrition (EEN), the Specific Carbohydrate Diet (SCD) and the low FODMAP diet. The literature on diet and IBD is reviewed with a particular focus on EEN, SCD, and low FODMAP diets. Lessons learned from the existing observations and strengths and shortcomings of existing data are presented.

Effect of cytomegalovirus and Epstein-Barr virus replication on intestinal mucosal gene expression and microbiome composition of HIV-infected and uninfected individuals.

BACKGROUND: HIV-infection is associated with dramatic changes in the intestinal mucosa. The impact of other viral pathogens is unclear. METHODS: One hundred and eight (108) biopsies from left and right colon (n = 79) and terminal ileum (n = 29) were collected from 19 HIV-infected and 22 HIV-uninfected participants. Levels of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA were measured by droplet digital PCR. Mucosal gene expression was measured via multiplex-assay. Microbiome analysis was performed using bacterial 16S-rDNA-pyrosequencing. The effect of CMV and EBV replication on the microbiome composition and mRNA-expression of selected cytokines (IL-6, IFN-γ, IL-1ß, CCL2, IL-8, and IFN-ß1) was evaluated. RESULTS: Overall, CMV and EBV were detected in at least one intestinal site in 60.5 and 78.9% of participants, respectively. HIV-infected individuals demonstrated less detectable CMV (PB = 0.02); CMV was more frequently detected in terminal ileum than colon (PB = 0.05). Detectable EBV was more frequent among HIV-infected (P B= 0.04) without differences by intestinal site. The number of operational taxonomic units did not differ by CMV or EBV detection status. Among HIV-infected participants, higher CMV was only associated with lower relative abundance of Actinobacteria in the ileum (P = 0.03). Presence of CMV was associated with upregulated expression of all selected cytokines in the ileum (all P < 0.02) and higher expression of IL-8 and IFN-ß1 in the colon (all P < 0.05) of HIV-uninfected participants, but not among HIV-infected. EBV had no effect on cytokine expression or microbiome composition whatsoever. CONCLUSION: These results illustrate a complex interplay among HIV-infection, intestinal CMV replication, and mucosal gut environment, and highlight a possible modulatory effect of CMV on the microbial and immune homeostasis.

Relationships between gastrointestinal microbiota and blood group antigens.

FUT2 is a gene for a fucosyltransferase that encodes expression of ABO blood group antigens found on gastrointestinal mucosa and secretions. We hypothesized that the fecal microbiomes of healthy subjects, with blood group antigens A, B, and O, have differing compositions. We analyzed 33 fecal and blood specimens from healthy subjects for FUT2 genotype, and the fecal microbiome was determined by 454 pyrosequencing. Our data show that being a blood group secretor is associated with less diversity at higher orders of taxonomy; and the presence of blood group A antigens in the secretor subjects are associated with an expansion families of bacteria within the gut. Furthermore, our study confirms the previous findings that secretors and nonsecretors have differing bacterial taxa. This extends the previous findings by demonstrating that the impact of being a nonsecretor is higher than that of individual blood group antigens. Additionally, we demonstrate that both secretor status and blood group antigen expression especially affect the Lachnospiraceae family of bacteria within the gut microbiome, with lower abundances noted in nonsecretors and higher abundances in secretors of various blood groups. We further note specific differences in blood group A-secretors demonstrating that the genus Blautia is lower in the group A-secretors compared with the non-A-secretors and that this reduction is accompanied by higher abundances of members of the Rikenellaceae, Peptostreptococcaceae, Clostridiales, and Turicibacter This study offers a first insight into the relationship between the fecal microbiome and blood group antigens in secretors.