Specific bacterial co-abundance groups are associated with inflammatory status in patients with ulcerative colitis.

BACKGROUND AND AIMS: While there is increasing interest in microbiome-directed therapies for patients with ulcerative colitis (UC), the identification of microbial targets remains elusive, underlining the need for novel approaches. METHODS: Utilizing metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease, available via the IBD Plexus Program of the Crohn's & Colitis Foundation, we used a tree-based dichotomous approach to assemble distinct clusters of species-level bacterial co-abundance groups (CAGs). We evaluated the abundance of bacterial CAGs and fungal taxa during remission (n=166) and activity (n=46). We examined if the bacterial CAGs identified in our cohorts were conserved in 2 healthy cohorts and in a Korean UC cohort. RESULTS: CAG3 and CAG8, dominated by bacteria from family Lachnospiraceae, were associated with remission. Low CAG8 and elevated Candida genus were predictive of active UC. Constituents from CAG8 were influential hub species of the remission-associated microbial UC network, including Ruminococcus gnavus, Erysipelatoclostridium ramosum, Blautia and Dorea species. These hub species interactions were preserved in 2 healthy cohorts and were partially recapitulated in a Korean UC cohort. CAG8 abundance correlated with the secondary bile acid production pathway. Bacterial CAGs did not correlate with Candida, however Bifidobacterium adolescentis and Alistipes putredinis were negatively associated with Candida. CONCLUSIONS: Lachnospiriceae-dominated bacterial CAGs were associated with remission in UC, with key bacterial interactions within the CAG also observed in 2 healthy cohorts and a Korean UC cohort. Bacterial CAG-based analyses may help to inform the design of candidate consortia for microbiome-based therapeutics.

Microbial butyrate capacity is reduced in inflamed mucosa in patients with ulcerative colitis.

Reduced butyrate-production capacity has been reported in fecal microbial communities in patients with active ulcerative colitis. However, the butyrate-production capacity of the mucosal microbiome from active vs quiescent mucosa in ulcerative colitis has been unexplored. We sought to determine the diversity and relative abundance of mucosal bacterial and fungal communities from endoscopically active vs quiescent mucosa in patients with UC, and aimed to predict contributions of mucosal microbial communities to butyrate synthesis. Systematic, segmental right- and left-sided biopsies were obtained from endoscopically active (n = 13) or quiescent (n = 17) colonic mucosa, among 15 patients with pan-colonic ulcerative colitis. Dietary fiber intake of patients was performed using the validated five-item FiberScreen questionnaire. Amplicon sequencing of mucosal bacteria and fungi was performed. The diversity and relative abundance of mucosal bacterial and fungal taxa were quantified, and predicted contributions to butyrate synthesis were ascertained. Bacterial alpha and beta diversity were similar between active vs quiescent mucosa. Butyrogenic taxa were significantly increased in quiescence, including Butyricimonas, Subdoligranulum, and Alistipes. Predicted butyrate kinase activity was significantly and concomitantly increased in quiescent mucosa. Fiber intake was positively correlated with butyrogenic microbes. Compared to mucosal bacterial prevalence, mucosal fungi were detected in low prevalence. Butyrogenic microbes are relatively increased in quiescent mucosa in ulcerative colitis, and may be related to increased fiber intake during quiescence. Manipulation of the mucosal microbiome towards butyrate-producing bacteria may be associated with endoscopic quiescence.

Colorectal Neoplasia in Asian Americans Undergoing First Time Asymptomatic Average-risk Screening Colonoscopies.

GOALS: We identified the prevalence and subtype of colorectal neoplasia removed during index screening colonoscopies in a large Asian American population. BACKGROUND: Asian Americans are the fastest growing demographic group in the United States yet there is a paucity of data on the characteristics of colorectal neoplasia found in this cohort. STUDY: Cross-sectional study of 2208 index colonoscopies performed on average-risk Asian and White patients at a large, tertiary academic center. Patients were identified via diagnostic or procedure codes between 2015 and 2020, with retrospective classification of polyp histopathology. Univariate and multivariate analysis were performed to identify risk factors associated with colorectal neoplasia. RESULTS: A total of 2208 patients were identified, of which 1085 were Asian. When adjusted for age and sex, Asians were as likely as Whites to have any type of colorectal neoplasia [44.2% vs. 43.5%, odds ratio (OR)=0.93, (CI: 0.78-1.11)]. On multivariate analysis, Asians were less likely to have sessile serrated polyps (5.5% vs. 9.9%, OR=0.53, 95% CI: 0.38-0.73) and more likely to have tubular adenomas in the left colon (22.6% vs. 18.0%, OR=1.33, 95% CI: 1.08-1.64) compared with Whites. CONCLUSIONS: Quality measures, such as sessile serrated polyp detection rates, may need to take into account demographic factors such as race. The prevalence of colorectal neoplasia among Asian Americans is substantial and warrants efforts to promote optimal uptake of colorectal cancer screening tests.

Dynamics of the Gut Mycobiome in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Intestinal fungi have been implicated in the pathogenesis of ulcerative colitis (UC). However, it remains unclear if fungal composition is altered during active versus quiescent disease. METHODS: We analyzed clinical and metagenomic data from the Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD), available via the IBD Plexus Program of the Crohn's & Colitis Foundation. We evaluated the fungal composition of fecal samples from 421 patients with UC during clinical activity and remission. Within a longitudinal subcohort (n = 52), we assessed for dynamic taxonomic changes across alterations in clinical activity over time. We examined if fungal amplicon sequence variants and fungal-bacterial relationships were altered during activity versus remission. Finally, we classified activity in UC using a supervised machine learning random forest model trained on fungal abundance data. RESULTS: During clinical activity, the relative abundance of genus Candida was increased 3.5-fold (P-adj < 1 × 10-4) compared with during remission. Patients with longitudinal reductions in clinical activity demonstrated parallel reductions in Candida relative abundance (P < .05). Candida relative abundance correlated with Parabacteroides diastonis, Faecalibacterium prausnitzii, and Bacteroides dorei relative abundance (P < .05) during remission; however, these correlations were disrupted during activity. Fungal abundance data successfully classified patients with active or quiescent UC (area under the curve ∼0.80), with Candida relative abundance critical to the success of the model. CONCLUSIONS: Clinical activity in UC is associated with an increased relative abundance of Candida, cross-sectionally and dynamically over time. The role of fecal Candida as a target for therapeutics in UC should be evaluated.

Elevated Total Serum Immunoglobulin A Levels in Patients with Suspicion for Celiac Disease.

Patients with classic symptoms of celiac disease are often initially tested for serum tissue transglutaminase-immunoglobulin A (tTG-IgA) and total serum immunoglobulin A (IgA) levels concurrently, as IgA deficiency can lead to falsely low tTG-IgA. There are no guidelines for incidental findings of elevated total serum IgA when testing for celiac disease. In our study, we described the proportion of patients with suspicion of celiac disease who had elevated total serum IgA and the factors that may be associated with these findings. We studied the management of these patients with incidental findings of elevated total serum IgA to identify its clinical significance. To investigate, we performed a retrospective chart review of patients who underwent celiac disease serologic testing at a single clinic from January 2017 to June 2022. We reported further laboratory workup and follow-up for patients with incidental findings of elevated total serum IgA by board-certified immunologists. In our chart review, 848 patients were identified, 85 (10.0%) of whom were found to be negative for celiac disease but had elevated total serum IgA levels (median IgA 351 mg/dL, interquartile range 324-382). Out of 85 patients, 73 were further evaluated by immunologists, with 55 patients undergoing additional laboratory workup. None were diagnosed with specific immunologic conditions. Male sex was identified as associated with elevated total serum IgA findings, and constipation was found in a statistically significant greater frequency of patients with normal total serum IgA rather than elevated total serum IgA. To provide external validation of our findings, we created a second patient cohort within the Stanford Research Repository database. Out of 33,875 patients identified, a similarly high proportion of patients were negative for celiac disease but had elevated total serum IgA levels (9.3%, 3140 patients). In this separate patient cohort, male sex was also identified as being associated with elevated total serum IgA. Our study also provides preliminary evidence that patients with incidental findings of elevated total serum IgA may not need further management or workup, as these abnormalities may not be clinically relevant without other clinical suspicions.

Alterations in the Fungal Microbiome in Ulcerative Colitis.

BACKGROUND: Although gut fungi have been implicated in the immunopathogenesis of inflammatory bowel disease, the fungal microbiome has not been deeply explored across endohistologic activity and treatment exposure in ulcerative colitis. METHODS: We analyzed data from the SPARC IBD (Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease) registry. We evaluated the fungal composition of fecal samples from 98 patients with ulcerative colitis across endoscopic activity (n = 43), endohistologic activity (n = 41), and biologic exposure (n = 82). Across all subgroups, we assessed fungal diversity and differential abundance of taxonomic groups. RESULTS: We identified 500 unique fungal amplicon sequence variants across the cohort of 82 patients, dominated by phylum Ascomycota. Compared with endoscopic remission, patients with endoscopic activity had increased Saccharomyces (log2 fold change = 4.54; adjusted P < 5 × 10-5) and increased Candida (log2 fold change = 2.56; adjusted P < .03). After adjusting for age, sex, and biologic exposure among patients with endoscopic activity, Saccharomyces (log2 fold change = 7.76; adjusted P < 1 × 10-15) and Candida (log2 fold change = 7.28; adjusted P< 1 × 10-8) remained enriched during endoscopic activity compared with quiescence. CONCLUSIONS: Endoscopic inflammation in ulcerative colitis is associated with an expansion of Saccharomyces and Candida compared with remission. The role of these fungal taxa as potential biomarkers and targets for personalized approaches to therapeutics in ulcerative colitis should be evaluated.

Gut fungi have been implicated in the pathogenesis of ulcerative colitis. In this retrospective study utilizing deep sequencing of the fecal fungal microbiome, Saccharomyces and Candida were increased during endoscopic inflammation and Penicillium was increased during endoscopic remission.

Characterizing the Reaction of Doctors to COVID-19 on Twitter.

With the recent surges of new COVID-19 variants, clear public health messaging on social media has become more vital than ever. One important source of public health information are messages and reactions expressed by medical professionals. However, the content of messages promogulated by these experts are not fully understood. In this study, we demonstrate how unique Twitter data can be used to explore doctors' reactions to the early months of the COVID-19 pandemic. We examine 265,412 English-language tweets about COVID-19 from doctors and a comparable subset of tweets from non-doctors using two-sample t-tests with a Bonferroni-corrected significance threshold. We elucidate how discussion differed over time and in comparison to non-doctors. Tweets spiked surrounding major events and in locations with rising case numbers. Discussion from doctors initially focused on the origin of the virus in Wuhan, later switching to calls to "stay home." Doctors tweeted more often about public health and healthcare workers, whereas non-doctors were more likely to tweet about political topics, including China and the Trump administration. The differences in how doctors and non-doctors engage about COVID-19 can provide insight into the similarities and differences in communication between medical experts and the public. For example, in future surges, experts could tailor their health messaging around topics of interest to the general public to increase engagement. Alternatively, topics that differ across groups may warrant educational messages to better align expert and public perspectives. By identifying both areas of shared purpose and differences in prioritized topics, future public health communications may benefit from analyses that compare the social media messages promulgated by various groups.

Splenomegaly, Non-Traumatic Splenic Rupture, and Pancytopenia in Patient with Human Granulocytic Anaplasmosis.

BACKGROUND: Splenic rupture is a well-described complication of babesiosis but is rarely associated with anaplasmosis. CASE PRESENTATION: We report a case of a 37-year-old man with no significant past medical history who presented with malaise, myalgias, arthralgias and severe left upper quadrant pain. He was found to have splenic rupture secondary to infection by Anaplasma phagocytophilum. He reported a single tick bite the week prior to onset of his symptoms. On presentation, he was found to have left upper quadrant abdominal tenderness, pancytopenia, and splenomegaly with evidence of splenic rupture and hemoperitoneum on contrasted computed tomography. Blood smear did not demonstrate intraerythrocytic parasites or morulae. His hemoperitoneum was treated conservatively and he was empirically treated for babesiosis. Diagnosis was confirmed by a positive serum PCR for Anaplasma phagocytophilum. CONCLUSIONS: This case study adds to the small number of prior case reports and provides evidence for anaplasmosis-associated splenic rupture.

Federally mandating motorcycle helmets in the United States.

BACKGROUND: Motorcycle helmets reduce both motorcycle-related fatalities and head injuries. Motorcycle crashes are a major public health concern which place economic stress on the U.S. healthcare system. DISCUSSION: Although statewide universal motorcycle helmet laws effectively increase helmet use, most state helmet laws do not require every motorcycle rider to wear a helmet. Herein, we propose and outline the solution of implementing federal motorcycle helmet law, while addressing potential counterarguments. CONCLUSIONS: The decision to ride a motorcycle without a helmet has consequences that affect more than just the motorcyclist. In an effort to prevent unnecessary healthcare costs, injuries, and deaths, public health efforts to increase helmet use through education and legislation should be strongly considered. Helmet use on motorcycles fits squarely within the purview of the federal government public health and economic considerations.