Spatial Characteristics of Colonic Mucosa-Associated Gut Microbiota in Humans.

Limited data exist on the spatial distribution of the colonic bacteria in humans. We collected the colonic biopsies from five segments of 27 polyp-free adults and collected feces from 13 of them. We sequenced the V4 region of the bacterial 16S rRNA gene using the MiSeq platform. The sequencing data were assigned to the amplicon sequence variant (ASV) using SILVA. Biodiversity and the relative abundance of the ASV were compared across the colonic segments and between the rectal and fecal samples. Bacterial functional capacity was assessed using Tax4fun. Each individual had a unique bacterial community composition (Weighted Bray-Curtis P value = 0.001). There were no significant differences in richness, evenness, community composition, and the taxonomic structure across the colon segments in all the samples. Firmicutes (47%), Bacteroidetes (39%), and Proteobacteria (6%) were the major phyla in all segments, followed by Verrucomicrobia, Fusobacteria, Desulfobacterota, and Actinobacteria. There were 15 genera with relative abundance > 1%, including Bacteroides, Faecalibacterium, Escherichia/Shigella, Sutterella, Akkermansia, Parabacteroides, Prevotella, Lachnoclostridium, Alistipes, Fusobacterium, Erysipelatoclostridium, and four Lachnospiraceae family members. Intra-individually, the community compositional dissimilarity was the greatest between the cecum and the rectum. There were significant differences in biodiversity and the taxonomic structure between the rectal and fecal bacteria. The bacterial community composition and structure were homogeneous across the large intestine in adults. The inter-individual variability of the bacteria was greater than inter-segment variability. The rectal and fecal bacteria differed in the community composition and structure.

Dietary quality and the colonic mucosa-associated gut microbiome in humans.

BACKGROUND: Despite tremendous interest in modulating the microbiome to improve health, the association between diet and the colonic mucosa-associated gut microbiome in healthy individuals has not been examined. OBJECTIVE: To investigate the associations between Healthy Eating Index (HEI)-2005 and the colonic mucosa-associated microbiota. METHODS: In this cross-sectional observational study, we analyzed bacterial community composition and structure using 16S rRNA gene (V4 region) sequencing of 97 colonic mucosal biopsies obtained endoscopically from different colon segments of 34 polyp-free participants. Dietary consumption was ascertained using an FFQ. Differences in α- and ß-diversity and taxonomic relative abundances between the higher and lower score of total HEI and its components were compared, followed by multivariable analyses. RESULTS: The structure of the microbiota significantly differed by the scores for total HEI, total and whole fruits (HEI 1 and HEI 2), whole grains (HEI 6), milk products and soy beverages (HEI 7), and solid fat, alcohol, and added sugar (HEI 12). A lower score for total HEI and HEIs 2, 7, and 12 was associated with significantly lower richness. A lower score for total HEI was associated with significantly reduced relative abundance of Parabacteroides, Roseburia, and Subdoligranulum but higher Fusobacterium. A lower score for HEI 2 was associated with lower Roseburia but higher Bacteroides. A lower score for HEI 7 was associated with lower Faecalibacterium and Fusobacterium but higher Bacteroides. A lower score for HEI 12 was associated with lower Subdoligranulum but higher Escherichia and Fusobacterium (false discovery rate-adjusted P values <0.05). The findings were confirmed by multivariate analysis. Less abundant bacteria such as Alistipes, Odoribacter, Bilophila, and Tyzzerella were also associated with dietary quality. CONCLUSIONS: A lower score for total HEI-2005 was significantly associated with reduced relative abundance of potentially beneficial bacteria but increased potentially harmful bacteria in the colonic mucosa of endoscopically normal individuals.

Dietary Nutrients Involved in One-Carbon Metabolism and Colonic Mucosa-Associated Gut Microbiome in Individuals with an Endoscopically Normal Colon.

One carbon (1C) metabolism nutrients influence epigenetic regulation and they are supplied by diet and synthesized by gut microbiota. We examined the association between dietary consumption of methyl donors (methionine, betaine and choline) and B vitamins (folate, B2, B6, and B12) and the community composition and structure of the colonic mucosa-associated gut microbiota determined by 16S rRNA gene sequencing in 97 colonic biopsies of 35 men. We used the food frequency questionnaire to assess daily consumption of nutrients, and the UPARSE and SILVA databases for operational taxonomic unit classification. The difference in bacterial diversity and taxonomic relative abundance were compared between low versus high consumption of these nutrients. False discover rate (FDR) adjusted p value < 0.05 indicated statistical significance. The bacterial richness and composition differed significantly by the consumption of folate and B vitamins (p < 0.001). Compared with higher consumption, a lower consumption of these nutrients was associated with a lower abundance of Akkermansia (folate), Roseburia (vitamin B2), and Faecalibacterium (vitamins B2, B6, and B12) but a higher abundance of Erysipelatoclostridium (vitamin B2) (FDR p values < 0.05). The community composition and structure of the colonic bacteria differed significantly by dietary consumption of folate and B vitamins.

Missed Opportunities for Screening and Surveillance of Barrett's Esophagus in Veterans with Esophageal Adenocarcinoma.

BACKGROUND: Barrett's esophagus (BE) is the premalignant lesion of esophageal adenocarcinoma (EAC) and is the target of early detection and prevention efforts for EAC. AIMS: We sought to evaluate what proportion and temporal trends of EAC patients had missed opportunities for screening and surveillance of BE. METHODS: Our study included 182 patients with EAC at the Michael E. DeBakey VA Medical Center in Houston, Texas, between 02/2005 and 09/2017. We conducted a retrospective audit of patients' medical records for any previous upper endoscopies (EGDs) for screening or surveillance of BE prior to their EAC diagnosis. RESULTS: The mean age of the cohort was 67.3 years (SD = 9.5); 99.5% of patients were male, and 85.2% were white. Only 45 patients (24.7%) had EGD at any time prior to the cancer diagnosing EGD, of whom 29 (15.9% of all EAC cases) had an established BE diagnosis. In the 137 patients with no prior EGD, most (63.5%) had GERD or were obese or ever smokers. There were no changes in patterns over time. For the 29 patients with prior established BE, 22 (75.8%) were diagnosed with EAC as a result of surveillance EGD. Patients with prior established BE were more likely to be diagnosed at 0 or I stage (p < 0.001) and managed with endoscopic or surgical modalities (p < 0.001) than patients without prior BE. CONCLUSIONS: Despite having established risk factors for BE, the majority of EAC patients had no prior EGD to screen for BE. BE screening may represent the largest missed opportunity to reduce EAC mortality.

Nonalcoholic fatty liver disease is underrecognized in the primary care setting.

OBJECTIVES: The prevalence and disease burden of nonalcoholic fatty liver disease (NAFLD) are increasing. Nonetheless, little is known about the processes related to identification, diagnosis, and referral of patients with NAFLD in routine clinical care. METHODS: Using automated data, we isolated a random sample of patients in a Veterans Administration facility who had ≥2 alanine transaminase (ALT) values >40 IU/ml >6 months apart in the absence of any positive results for hepatitis C RNA, hepatitis B surface antigen, or screens for excess alcohol use. We conducted a structured medical record review to confirm NAFLD and abstracted data from the primary care providers' notes for (i) recognition of abnormal ALT levels, (ii) mention of NAFLD as a possible diagnosis, (iii) recommendations for diet or exercise, and (d) referral to a specialist for further NAFLD evaluation. Using a multilevel logistic regression model, we identified patient demographic, clinical, comorbidity, and health-care utilization factors associated with recognition and receipt of early NAFLD care. RESULTS: Of 251 patients identified with NAFLD by our methods, 99 (39.4%) had documentation in medical record notes of abnormal ALT, 54 (21.5%) had NAFLD mentioned as a possible diagnosis, 37 (14.7%) were counseled regarding diet and exercise, and 26 (10.4%) were referred to a specialist. Only the magnitude of ALT elevation (adjusted odds ratio (OR) for ALT >80 IU/ml vs. <80 IU/ml=4.4, 95% confidence interval (CI)=2.65-7.30) and proportion of elevation (adjusted OR for >50% vs. <50% of ALT values >40 IU/ml=1.8, 95% CI=1.03-3.14) were associated with receiving specified NAFLD care. Only 3% of patients at a high risk of fibrosis (NAFLD fibrosis score >0.675) were referred to specialists. CONCLUSIONS: Most patients in care who may have NAFLD are not being recognized and evaluated for this condition. Our data suggest that providers may be using an incorrect heuristic in delivering NAFLD care by concentrating on those with high ALT levels.

Neopterin concentration as an index of disease activity in Crohn's disease and ulcerative colitis.

BACKGROUND: Neopterin, a pyrazino-[2,3-d]-pyrimidine compound, is a metabolite of cyclic guanosine monophosphate that is released by activated T lymphocytes and macrophages after induction by γ interferon. We sought to determine whether neopterin concentration in stool, serum, or urine is a useful marker of disease activity in patients with Crohn's disease or ulcerative colitis. METHODS: We prospectively studied 70 outpatients (33 M, 37 F, aged 39.2 ± 14.0 y) with Crohn's disease (33 clinically in remission, 37 active), 52 outpatients (29 M, 23 F, aged 39.8 ± 12.2 y) with ulcerative colitis (29 clinically in remission, 23 active), and 141 healthy control subjects. Fecal, serum, and urine samples were analyzed for neopterin concentration and other analytes of interest. The following clinical indices were calculated at enrollment: for Crohn's disease, the Capetown Index and Harvey Bradshaw Index; for ulcerative colitis, Simple Clinical Colitis Activity Index, Disease Activity Index, and endoscopic disease severity (rated on a scale of 0 to 3). Crohn's disease was considered active if the Harvey Bradshaw Index was ≥ 5, and ulcerative colitis was considered active if the Simple Clinical Colitis Activity Index was >3. RESULTS: Among Crohn's disease patients, fecal neopterin was higher in those with either clinically active (96.0 ng/g) or inactive (87.2 ng/g) disease than in control subjects (12.0 ng/g; P<0.05; inactive or active disease vs. controls). For ulcerative colitis patients, fecal neopterin concentration was higher in those with active (135.2 ng/g) disease than in those with inactive disease (62.7 ng/g; P<0.05) or healthy controls (12.0 ng/g; P<0.05). Neither serum nor urine neopterin concentrations were increased in patients with active inflammatory bowel disease. Nonsignificant trends toward greater fecal neopterin concentration were observed with increased colonic disease involvement, although not with endoscopic severity or clinical disease activity indices. CONCLUSIONS: Fecal neopterin concentration is increased in patients with clinically active or inactive Crohn's disease and in patients with clinically active ulcerative colitis when compared with controls, and therefore represents a new biomarker for disease activity.