Disease-specific alterations in the enteric virome in inflammatory bowel disease.

Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn's disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease and cohort specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases.

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.

Quantum Contagion: A Quantum-Like Approach for the Analysis of Social Contagion Dynamics with Heterogeneous Adoption Thresholds.

Modeling the information of social contagion processes has recently attracted a substantial amount of interest from researchers due to its wide applicability in network science, multi-agent-systems, information science, and marketing. Unlike in biological spreading, the existence of a reinforcement effect in social contagion necessitates considering the complexity of individuals in the systems. Although many studies acknowledged the heterogeneity of the individuals in their adoption of information, there are no studies that take into account the individuals' uncertainty during their adoption decision-making. This resulted in less than optimal modeling of social contagion dynamics in the existence of phase transition in the final adoption size versus transmission probability. We employed the Inverse Born Problem (IBP) to represent probabilistic entities as complex probability amplitudes in edge-based compartmental theory, and demonstrated that our novel approach performs better in the prediction of social contagion dynamics through extensive simulations on random regular networks.

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.

Race-dependent association of sulfidogenic bacteria with colorectal cancer.

OBJECTIVE: Colorectal cancer (CRC) incidence is higher in African Americans (AAs) compared with non-Hispanic whites (NHWs). A diet high in animal protein and fat is an environmental risk factor for CRC development. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC. Hydrogen sulfide, produced by autochthonous sulfidogenic bacteria, triggers proinflammatory pathways and hyperproliferation, and is genotoxic. We hypothesised that sulfidogenic bacterial abundance in colonic mucosa may be an environmental CRC risk factor that distinguishes AA and NHW. DESIGN: Colonic biopsies from uninvolved or healthy mucosa from CRC cases and tumour-free controls were collected prospectively from five medical centres in Chicago for association studies. Sulfidogenic bacterial abundance in uninvolved colonic mucosa of AA and NHW CRC cases was compared with normal mucosa of AA and NHW controls. In addition, 16S rDNA sequencing was performed in AA cases and controls. Correlations were examined among bacterial targets, race, disease status and dietary intake. RESULTS: AAs harboured a greater abundance of sulfidogenic bacteria compared with NHWs regardless of disease status. Bilophila wadsworthia-specific dsrA was more abundant in AA cases than controls. Linear discriminant analysis of 16S rRNA gene sequences revealed five sulfidogenic genera that were more abundant in AA cases. Fat and protein intake and daily servings of meat were significantly higher in AAs compared with NHWs, and multiple dietary components correlated with a higher abundance of sulfidogenic bacteria. CONCLUSIONS: These results implicate sulfidogenic bacteria as a potential environmental risk factor contributing to CRC development in AAs.

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.

Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice.

BACKGROUND & AIMS: Alcoholic liver disease is a leading cause of mortality. Chronic alcohol consumption is accompanied by intestinal dysbiosis, and development of alcoholic liver disease requires gut-derived bacterial products. However, little is known about how alterations to the microbiome contribute to pathogenesis of alcoholic liver disease. METHODS: We used the Tsukamoto-French mouse model, which involves continuous intragastric feeding of isocaloric diet or alcohol for 3 weeks. Bacterial DNA from the cecum was extracted for deep metagenomic sequencing. Targeted metabolomics assessed concentrations of saturated fatty acids in cecal contents. To maintain intestinal metabolic homeostasis, diets of ethanol-fed and control mice were supplemented with saturated long-chain fatty acids (LCFA). Bacterial genes involved in fatty acid biosynthesis, amounts of lactobacilli, and saturated LCFA were measured in fecal samples of nonalcoholic individuals and patients with active alcohol abuse. RESULTS: Analyses of intestinal contents from mice revealed alcohol-associated changes to the intestinal metagenome and metabolome, characterized by reduced synthesis of saturated LCFA. Maintaining intestinal levels of saturated fatty acids in mice resulted in eubiosis, stabilized the intestinal gut barrier, and reduced ethanol-induced liver injury. Saturated LCFA are metabolized by commensal Lactobacillus and promote their growth. Proportions of bacterial genes involved in fatty acid biosynthesis were lower in feces from patients with active alcohol abuse than controls. Total levels of LCFA correlated with those of lactobacilli in fecal samples from patients with active alcohol abuse but not in controls. CONCLUSIONS: In humans and mice, alcohol causes intestinal dysbiosis, reducing the capacity of the microbiome to synthesize saturated LCFA and the proportion of Lactobacillus species. Dietary approaches to restore levels of saturated fatty acids in the intestine might reduce ethanol-induced liver injury in patients with alcoholic liver disease.

A compositional look at the human gastrointestinal microbiome and immune activation parameters in HIV infected subjects.

HIV progression is characterized by immune activation and microbial translocation. One factor that may be contributing to HIV progression could be a dysbiotic microbiome. We therefore hypothesized that the GI mucosal microbiome is altered in HIV patients and this alteration correlates with immune activation in HIV. 121 specimens were collected from 21 HIV positive and 22 control human subjects during colonoscopy. The composition of the lower gastrointestinal tract mucosal and luminal bacterial microbiome was characterized using 16S rDNA pyrosequencing and was correlated to clinical parameters as well as immune activation and circulating bacterial products in HIV patients on ART. The composition of the HIV microbiome was significantly different than that of controls; it was less diverse in the right colon and terminal ileum, and was characterized by loss of bacterial taxa that are typically considered commensals. In HIV samples, there was a gain of some pathogenic bacterial taxa. This is the first report characterizing the terminal ileal and colonic mucosal microbiome in HIV patients with next generation sequencing. Limitations include use of HIV-infected subjects on HAART therapy.

Longitudinal Survey of Microbiota in Hospitalized Preterm Very-Low-Birth-Weight Infants.

OBJECTIVES: The aim of the present study was to examine the changes in bacteria in hospitalized preterm infants during the first month of life. METHODS: Rectal swabs were collected daily from 12 preterm infants. DNA was extracted from swabs from day of birth and weekly thereafter. Bacterial taxa were identified with next generation sequencing using universal bacterial primers targeted at the 16S ribosomal DNA on a 454 Roche titanium platform. Sequences were clustered into operational taxonomic units, and taxonomy was assigned against the Greengenes databank using Quantitative Insights Into Microbial Ecology version 1.4. Quantitative polymerase chain reaction was used to determine the abundance of Bifidobacterium spp. Functional assessment of the microbiome was performed with Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). RESULTS: Average birth weight and gestational age were 1055 g and 28 weeks, respectively. There were 6 to 35 different bacterial families identified in the day-of-birth samples, unrelated to the mode of delivery. Richness decreased through hospitalization (week 1, 16.9 ±â€Š7.7 vs weeks 3-5, 10.7 ±â€Š3.4, P < 0.001). The Shannon diversity index demonstrated the lowest diversity at birth, an increase at week 2, followed by a rapid decline at weeks 3 to 5, suggesting the development of a more uniform microbiota composition after 2 weeks of stay at a neonatal intensive care unit. Enterobacteriaceae, Staphylococcaceae, and Enterococcaceae constituted the majority of the bacterial families. Bifidobacterium spp were infrequently detected at extremely low levels. PICRUSt analysis revealed the enhancement of peroxisome, PPAR, and adipocytokine signaling; plant-pathogen interaction; and aminobenzoate degradation pathways in week 1 samples. CONCLUSIONS: Our results suggest that although preterm infants have individualized microbiota that are detectable at birth, the differences decrease during the neonatal intensive care unit hospitalization with increasing prominence of pathogenic microbiota.

Breath Methane Levels Are Increased Among Patients with Diverticulosis.

BACKGROUND: Diverticulosis and its complications are important healthcare problems in the USA and throughout the Western world. While mechanisms as to how diverticulosis occurs have partially been explored, few studies examined the relationship between colonic gases such as methane and diverticulosis in humans. AIM: This study aimed to demonstrate a significant relationship between methanogenic Archaea and development of diverticulosis. METHODS: Subjects who consecutively underwent hydrogen breath test at Rush University Medical Center between 2003 and 2010 were identified retrospectively through a database. Medical records were reviewed for presence of a colonoscopy report. Two hundred and sixty-four subjects were identified who had both a breath methane level measurement and a colonoscopy result. Additional demographic and clinical data were obtained with chart review. RESULTS: Mean breath methane levels were higher in subjects with diverticulosis compared to those without diverticulosis (7.89 vs. 4.94 ppm, p = 0.04). Methane producers (defined as those with baseline fasting breath methane level >5 ppm) were more frequent among subjects with diverticulosis compared to those without diverticulosis (50.9 vs. 34 %, p = 0.0025). When adjusted for confounders, breath methane levels and age were the two independent predictors of diverticulosis on colonoscopy with logistic regression modeling. CONCLUSIONS: Methanogenesis is associated with the presence of diverticulosis. Further studies are needed to confirm our findings and prospectively evaluate a possible etiological role of methanogenesis and methanogenic archaea in diverticulosis.

Colonic bacterial composition in Parkinson's disease.

INTRODUCTION: We showed that Parkinson's disease (PD) patients have alpha-synuclein (α-Syn) aggregation in their colon with evidence of colonic inflammation. If PD patients have altered colonic microbiota, dysbiosis might be the mechanism of neuroinflammation that leads to α-Syn misfolding and PD pathology. METHODS: Sixty-six sigmoid mucosal biopsies and 65 fecal samples were collected from 38 PD patients and 34 healthy controls. Mucosal-associated and feces microbiota compositions were characterized using high-throughput ribosomal RNA gene amplicon sequencing. Data were correlated with clinical measures of PD, and a predictive assessment of microbial community functional potential was used to identify microbial functions. RESULTS: The mucosal and fecal microbial community of PD patients was significantly different than control subjects, with the fecal samples showing more marked differences than the sigmoid mucosa. At the taxonomic level of genus, putative, "anti-inflammatory" butyrate-producing bacteria from the genera Blautia, Coprococcus, and Roseburia were significantly more abundant in feces of controls than PD patients. Bacteria from the genus Faecalibacterium were significantly more abundant in the mucosa of controls than PD. Putative, "proinflammatory" Proteobacteria of the genus Ralstonia were significantly more abundant in mucosa of PD than controls. Predictive metagenomics indicated that a large number of genes involved in metabolism were significantly lower in the PD fecal microbiome, whereas genes involved in lipopolysaccharide biosynthesis and type III bacterial secretion systems were significantly higher in PD patients. CONCLUSION: This report provides evidence that proinflammatory dysbiosis is present in PD patients and could trigger inflammation-induced misfolding of α-Syn and development of PD pathology.

Risk factors for severe or fatal drug-induced liver injury from amoxicillin-clavulanic acid.

AIM: To identify risk factors for severe liver injury or mortality from drug-induced liver injury (DILI) from amoxicillin-clavulanic acid. To determine if co-administration of potentially hepatotoxic drugs was associated with an increased risk of DILI from amoxicillin-clavulanic acid. METHODS: We conducted a systematic review of the published work and data extraction of articles on DILI injury from amoxicillin-clavulanic acid. Potentially hepatotoxic drugs were defined as medications with DILI listed in the package insert or reported in the published work. Individual patient data were entered into an SPSS (version 17.0; Chicago, IL, USA) database and were analyzed using the χ(2) -test or Fisher's exact test; Student's t-test; and non-parametric tests such as Mann-Whitney U-test as appropriate. RESULTS: We identified 3932 articles of which 41 publications with 255 reported cases met inclusion criteria. Mortality from DILI from amoxicillin-clavulanic acid was increased among patients receiving concomitant potentially hepatotoxic drugs compared with patients not on concomitant potential hepatotoxic drugs (21.4% [3/14] vs 2.3% [2/89], P = 0.017]. The most common classes of concomitant drugs were: antimicrobials, analgesics and hormonal therapy. Female patients were more likely to receive a concomitant potentially hepatotoxic medication (25% vs 9.1% for men, P = 0.05). CONCLUSION: Patients who developed severe or fatal DILI from amoxicillin-clavulanic acid were more likely to be on concomitant hepatotoxic medications. Female patients were more likely to receive concomitant hepatotoxic drugs. Further studies are needed to investigate drug interaction between amoxicillin-clavulanic acid and concomitant potentially hepatotoxic drugs.

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.

Racial and Ethnic Minorities With Acute Pancreatitis Live in Neighborhoods With Higher Social Vulnerability Scores.

OBJECTIVES: The primary objective was to determine differences in Social Vulnerability Index (SVI) scores among minorities (African-Americans and Hispanics) with acute pancreatitis (AP) compared with non-Hispanic whites (NHWs) with AP. The secondary objectives were to determine differences in diet, sulfidogenic bacteria gene copy numbers (gcn) and hydrogen sulfide (H2S) levels between the 2 groups. MATERIALS AND METHODS: Patients with AP were enrolled during hospitalization (n = 54). Patient residential addresses were geocoded, and the Centers for Disease Control and Prevention's SVI scores were appended. Dietary intake and serum H2S levels were determined. Microbial DNAs were isolated from stool, and gcn of sulfidogenic bacteria were determined. RESULTS: Minorities had higher SVI scores compared with NHWs ( P = 0.006). They also had lower consumption of beneficial nutrients such as omega-3 fatty acids [stearidonic ( P = 0.019), and eicosapentaenoic acid ( P = 0.042)], vitamin D ( P = 0.025), and protein from seafood ( P = 0.031). Lastly, minorities had higher pan-dissimilatory sulfite reductase A ( pan-dsrA ) gcn ( P = 0.033) but no significant differences in H2S levels ( P = 0.226). CONCLUSION: Minorities with AP have higher SVI compared with NHWs with AP. Higher SVI scores, lower consumption of beneficial nutrients, and increased gcn of pan-dsrA in minorities with AP suggest that neighborhood vulnerability could be contributing to AP inequities.

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.

Diet, Gut Microbiome, and Their End Metabolites Associate With Acute Pancreatitis Risk.

INTRODUCTION: Diet and decreased gut microbiome diversity has been associated with acute pancreatitis (AP) risk. However, differences in dietary intake, gut microbiome, and their impact on microbial end metabolites have not been studied in AP. We aimed to determine differences in (i) dietary intake (ii) gut microbiome diversity and sulfidogenic bacterial abundance, and (iii) serum short-chain fatty acid (SCFA) and hydrogen sulfide (H 2 S) concentrations in AP and control subjects. METHODS: This case-control study recruited 54 AP and 46 control subjects during hospitalization. Clinical and diet data and stool and blood samples were collected. 16S rDNA sequencing was used to determine gut microbiome alpha diversity and composition. Serum SCFA and H 2 S levels were measured. Machine learning (ML) model was used to identify microbial targets associated with AP. RESULTS: AP patients had a decreased intake of vitamin D 3 , whole grains, fish, and beneficial eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids. AP patients also had lower gut microbiome diversity ( P = 0.021) and a higher abundance of sulfidogenic bacteria including Veillonella sp. and Haemophilus sp., which were associated with AP risk. Serum acetate and H 2 S concentrations were significantly higher in the AP group ( P < 0.001 and P = 0.043, respectively). ML model had 96% predictive ability to distinguish AP patients from controls. DISCUSSION: AP patients have decreased beneficial nutrient intake and gut microbiome diversity. An increased abundance of H 2 S-producing genera in the AP and SCFA-producing genera in the control group and predictive ability of ML model to distinguish AP patients indicates that diet, gut microbiota, and their end metabolites play a key role in AP.

Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans: report of an expert meeting.

The present report summarizes the United States Department of Veterans Affairs (VA) field-based meeting titled "Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans." Our Veteran patient population experiences a high incidence of service-related chronic physical and mental health problems, such as infection, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), various forms of hematological and non-hematological malignancies, neurologic conditions, end-stage organ failure, requiring transplantation, and posttraumatic stress disorder (PTSD). We report the views of a group of scientists who focus on the current state of scientific knowledge elucidating the mechanisms underlying the aforementioned disorders, novel therapeutic targets, and development of new approaches for clinical intervention. In conclusion, we dovetailed on four research areas of interest: 1) microbiome interaction with immune cells after hematopoietic cell and/or solid organ transplantation, graft-versus-host disease (GVHD) and graft rejection, 2) intestinal inflammation and its modification in IBD and cancer, 3) microbiome-neuron-immunity interplay in mental and physical health, and 4) microbiome-micronutrient-immune interactions during homeostasis and infectious diseases. At this VA field-based meeting, we proposed to explore a multi-disciplinary, multi-institutional, collaborative strategy to initiate a roadmap, specifically focusing on host microbiome-immune interactions among those with service-related chronic diseases to potentially identify novel and translatable therapeutic targets.

Colonic microbiome is altered in alcoholism.

Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics.