Gut Microbiome and Lipidome Signatures in Irritable Bowel Syndrome Patients from a Low-Income, Food-Desert Area: A Pilot Study.

Irritable bowel syndrome (IBS) is a common gastroenterological disorder with triggers such as fructose. We showed that our IBS patients suffering from socioeconomic challenges have a significantly high consumption of high-fructose corn syrup (HFCS). Here, we characterize gut microbial dysbiosis and fatty acid changes, with respect to IBS, HFCS consumption, and socioeconomic factors. Fecal samples from IBS patients and healthy controls were subjected to microbiome and lipidome analyses. We assessed phylogenetic diversity and community composition of the microbiomes, and used linear discriminant analysis effect size (LEfSe), analysis of compositions of microbiomes (ANCOM) on highly co-occurring subcommunities (modules), least absolute shrinkage and selection operator (LASSO) on phylogenetic isometric log-ratio transformed (PhILR) taxon abundances to identify differentially abundant taxa. Based on a Procrustes randomization test, the microbiome and lipidome datasets correlated significantly (p = 0.002). Alpha diversity correlated with economic factors (p < 0.001). Multiple subsets of the phylogenetic tree were associated with HFCS consumption (p < 0.001). In IBS patients, relative abundances of potentially beneficial bacteria such as Monoglobaceae, Lachnospiraceae, and Ruminococcaceae were lower (p = 0.007), and Eisenbergiella, associated with inflammatory disorders, was higher. In IBS patients, certain saturated fatty acids were higher and unsaturated fatty acids were lower (p < 0.05). Our study aims first to underscore the influence of HFCS consumption and socioeconomic factors on IBS pathophysiology, and provides new insights that inform patient care.

Clinical Factors Implicated in Antibiotic Resistance in Helicobacter pylori Patients.

Helicobacter pylori is a common gastric pathogen associated with multiple clinical syndromes, including cancer. Eradication rates of H. pylori remain suboptimal despite the progress made in the past few decades in improving treatment strategies. The low eradication rates are mainly driven by antibiotic resistance of H. pylori. Non-invasive molecular testing to identify patients with antibiotic-resistant H. pylori represents a promising therapeutic avenue, however this technology currently remains limited by availability, costs, and lack of robust validation. Moreover, there is insufficient evidence to demonstrate that resistance-testing-based treatment approaches are superior to appropriately designed empiric strategies. Consensus guidelines recommend use of proven locally effective regimens; however, eradication data are inconsistently generated in several regions of the world. In this review, we describe several clinical factors associated with increased rates of antibiotic resistant H. pylori, including history of previous antibiotic exposure, increasing age, female gender, ethnicity/race, extent of alcohol use, and non-ulcer dyspepsia. Assessment of these factors may aid the clinician in choosing the most appropriate empiric treatment strategy for each patient. Future study should aim to identify locally effective therapies and further explore the clinical factors associated with antibiotic resistance.

Effects of Milkfat on the Gut Microbiome of Patients After Bariatric Surgery, a Pilot Study.

BACKGROUND: The efficacy of bariatric surgery may be in part attributed to altered metabolism via new gut microbiome. Milkfat may promote the growth of microbes that are beneficial in long-term weight loss. Understanding the specific gut microbiome changes after surgery and their relationship to milkfat consumption may yield important strategies for managing obesity after bariatric procedures. METHODS: In this pilot study, stool samples were collected from nine patients before and at the time of surgery, and at 1, 3, and 6 months post-surgery. At each time-point, dairy consumption was determined from dietary surveys. 16 s rRNA gene sequencing was performed followed by alpha diversity analysis. Comparisons of relative abundances of microbial taxa and analyses of fatty acids changes were performed. RESULTS: Bariatric surgery led to enrichment of (i) Roseburia, associated with weight loss and (ii) Christensenellaceae, inversely related to body mass index. High milk-fat consumption correlated with enrichment of Blautia, inversely associated with visceral fat accumulation. Faecalibacterium, possibly associated with obesity, increased in patients with low milk-fat consumption. Butter was associated with decreased alpha diversity in all subjects (p-value = 0.038) and the frequency of its use was associated with decreased alpha diversity in patients (correlation = - 0.68, p-value = 0.042). Low-milk-fat consumers showed higher concentration of saturated fatty acids. CONCLUSIONS: Our results suggest that incorporating dairy products in post-bariatric-surgery dietary plans may help cultivate a gut microbiome that is effective in regulating fat storage as well as digesting beneficial metabolites. These observations will be helpful for the management of obesity in general population as well.

Preoperative high-resolution esophageal manometry and postoperative symptoms in patients undergoing bariatric surgery: a retrospective cohort study.

BACKGROUND: The increasing incidence of obesity has led to a rise in bariatric surgeries. Obesity can be associated with various gastrointestinal symptoms as well as abnormal findings on high-resolution esophageal manometry (HRM). Bariatric procedures have variable effects on esophageal function and may contribute to postoperative symptoms. Preoperative HRM is not performed routinely on patients undergoing bariatric surgery but may identify patients likely to experience postoperative esophageal symptoms via delineation of structural or functional abnormalities. OBJECTIVES: To evaluate whether prebariatric surgery HRM could predict persistent or de novo postoperative esophageal symptoms. SETTING: Academic tertiary care hospital, United States. METHODS: Retrospective data were collected for 20 patients undergoing HRM and 100 controls 18 years and older from May 2012 to May 2015. Propensity score matching was performed to adjust for baseline differences between the 2 groups. Preoperative and postoperative esophageal symptoms (reflux, dysphagia, nausea/vomiting, bloating, fullness, early satiety, pain, and intolerance) were compared between HRM and control patients, and associations among HRM findings, Chicago Classification, and symptoms were analyzed. All included patients had follow-up beyond 3 months postoperatively. Data were analyzed with 2-tailed Fisher's exact test, Wilcoxon rank-sum test, and odds ratio. RESULTS: Compared to controls, patients undergoing preoperative HRM had a higher rate of postoperative chronic intolerance (25% versus 8%, P = .041). This difference was not observed in propensity score matching analysis. Identification of elevated integrated relaxation pressure and esophagogastric junction outflow obstruction predicted chronic intolerance (odds ratio = 21.0; 95% confidence interval: 1.40-314; P = .027 for each). CONCLUSIONS: Preoperative HRM abnormalities were associated with postoperative symptoms in patients undergoing bariatric surgery. HRM can identify patients who are more likely to experience postoperative esophageal symptoms and may aid in discussion of suitability for surgery and selection of bariatric intervention.

Characterization of gut microbiome and metabolome in Helicobacter pylori patients in an underprivileged community in the United States.

BACKGROUND: Helicobacter pylori (H. pylori), a bacterium that infects approximately half of the world's population, is associated with various gastrointestinal diseases, including peptic ulcers, non-ulcer dyspepsia, gastric adenocarcinoma, and gastric lymphoma. As the burden of antibiotic resistance increases, the need for new adjunct therapies designed to facilitate H. pylori eradication and reduce negative distal outcomes associated with infection has become more pressing. Characterization of the interactions between H. pylori, the fecal microbiome, and fecal fatty acid metabolism, as well as the mechanisms underlying these interactions, may offer new therapeutic approaches. AIM: To characterize the gut microbiome and metabolome in H. pylori patients in a socioeconomically challenged and underprivileged inner-city community. METHODS: Stool samples from 19 H. pylori patients and 16 control subjects were analyzed. 16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2. Alpha and beta diversity analyses were performed in QIIME 2. Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry, which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters. Multi-dimensional scaling (MDS) was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates. RESULTS: Fecal microbiome analysis showed that alpha diversity was lowest in H. pylori patients over 40 years of age compared to control subjects of similar age group. Beta diversity analysis of the samples revealed significant differences in microbial community structure between H. pylori patients and control subjects across all ages. Thirty-eight and six taxa had lower and higher relative abundance in H. pylori patients, respectively. Taxa that were enriched in H. pylori patients included Atopobium, Gemellaceae, Micrococcaceae, Gemellales and Rothia (R. mucilaginosa). Notably, relative abundance of the phylum Verrucomicrobia was decreased in H. pylori patients compared to control subjects. Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets. Stool samples from H. pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids (PUFAs) 22:4n6, 22:5n3, 20:3n6 and 22:2n6, while decreases were noted in other fatty acids including the PUFA 18:3n6. The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis. CONCLUSION: This exploratory study demonstrates H. pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism. Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.

Designing strategies for eradication of Helicobacter pylori based on prevalence patterns of infection and antibiotic resistance in a low-income, medically underserved community in the United States.

BACKGROUND: Regional variation in Helicobacter pylori resistance patterns is a significant contributing factor for the ineffectiveness of traditional treatments. To improve treatment outcomes, we sought to create an individualized, susceptibility-driven therapeutic approach among our patient population, which is one of the poorest in the nation. It is medically underserved, minority-predominant and has high incidence of H pylori infection. METHODS: We compiled various factors involved in the antibiotic resistance of H pylori from literature. We then created a predictive model to customize therapies based on analyzed data from 2,014 H pylori patients with respect to several of these factors. The predictions of the model were further tested with analysis of patient stool samples. RESULTS: A clear pattern of H pylori prevalence and antibiotic resistance was observed in our patients. We observed that majority of H pylori patients were women (62%) and over the age of 40 years (80%). 30% and 36% of the H pylori patients were African American and Hispanic, respectively. A median household income of less than $54,000, past H pylori infection, previous use of certain antibiotics for any infection decreased the chance of eradication. Results of the stool testing were consistent with model predictions (90% accuracy). CONCLUSION: This model demonstrates the predictive accuracy of H pylori infection and antibiotic resistance based on patient attributes and previous treatment history. It will be useful to formulate customized treatments with predicted outcomes to minimize failures. Our community attributes may contribute toward broad applicability of model for other similar communities.

Use of Real Patients and Patient-Simulation-Based Methodologies for Teaching Gastroenterology to Pre-Clinical Medical Students.

In recent years, there has been an increasing focus on the need to integrate formal knowledge with clinical experience in the pre-clinical years since the initial years of medical education play an important role in shaping the attitudes of medical students towards medicine and support the development of clinical reasoning. In this study, we describe approaches that involve real patients and patient-simulation-based methodologies to teach gastroenterology to second year medical students. Our goals were to (i) demonstrate bio-psychosocial aspects of clinical practice, (ii) demonstrate commonality of gastrointestinal ailments, and (iii) help understand complex gastroenterology concepts. We used two main approaches including brief, pre-prepared questions and answers discussing with the patients in various sessions throughout the course and a two-hour session that included patient participation, patient simulation modalities with high fidelity mannequins, a lightening round of interactive cases, and a Patient Oriented Problem Solving (POPS) session. The approaches improved the effectiveness of the delivery of the content-heavy, fast-paced GI course and provided opportunities for the students to think about gastroenterology from both basic and clinical points of view. The approaches involved peer teaching, which supports knowledge acquisition and comprehension. Very positive feedback and overall engagement of students suggested that these approaches were well-received.

Irritable Bowel Syndrome: Clinical Manifestations, Dietary Influences, and Management.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is characterized by symptoms of chronic abdominal pain and altered bowel habits in the absence of an overtly identifiable cause. It is the most commonly diagnosed functional gastrointestinal disorder, accounting for about one third of gastroenterology visits. It generally presents as a complex of symptoms, including psychological dysfunction. Hypersensitivity to certain foods, especially foods that contain high amounts of fructose, plays a role in the pathophysiology of IBS. Elevated consumption of high-fructose corn syrup (HFCS) has been discussed in this aspect. The treatment options for IBS are challenging and varied. In addition to dietary restrictions for HFCS-induced IBS, such as low-FODMAP (Fermentable Oligosaccharides, Disaccharide, Monosaccharides, and Polyols) diets, existing drug therapies are administered based on the predominant symptoms and IBS-subtype. Patients with IBS are likely to suffer from issues, such as anxiety, depression, and post-traumatic-stress disorder. Biopsychosocial factors particularly socioeconomic status, sex, and race should, thus, be considered for diagnostic evaluation of patients with IBS.

An Interactive Session on Nutritional Pathologies for Health Professional Students.

Various studies have emphasized the need to improve the nutrition training of health professionals, which will help them to provide optimal patient care. Nutrition-based interactive sessions may serve as an efficient approach to instigate an interest in nutrition among the students. Here we report the reception and effectiveness of a nutrition-pathology based interactive activity that we designed and implemented in the gastroenterology course given to the second year students at our medical school. The activity involved team work, individual accountability and peer-teaching. Nutrition pathology case stems (Kwashiorkor, vitamin B-12 deficiency, zinc deficiency and zinc-induced copper deficiency) were posted on the course website for the students to read before the session. At the start of the session, all the groups (each made up of four members) took a pre-quiz. Each student was then given an information sheet describing one case. Each group discussed the four cases with students acting as the "teacher" for the case assigned to them. A post-quiz was administered to the groups to assess acquisition of knowledge as well as in-depth thinking about the nutrition aspects discussed. The efficacy of the session measured by pre (39% questions correctly answered in total) and post-quizzes (96% questions correctly answered in total) and the overwhelmingly positive student feedback indicated that the session was highly effective. Ninety-five percent of students thought that the session demonstrated the clinical relevance of nutrition, while 98% students found the peer teaching to be engaging.

Tonic and phasic pyloric activity in response to CCK-octapeptide.

BACKGROUND: The purpose of this study was to determine whether a high-resolution solid-state catheter system could detect regional pressure changes within the antrum and pylorus in response to CCK-octapeptide. METHODS: Subjects received a 30 min infusion of CCK-octapeptide at either 0.02 or 0.06 microg kg(-1) h(-1). RESULTS: Five males and two females were studied. Mean antral pressure during phase I MMC increased from 5.3 +/- 2.1 to 9.9 +/- 2.4 mmHg (P = 0.028) after infusion. At the pylorus, only the 0.06 microg kg(-1) h(-1) dose increased tonic pressure (8.8 +/- 1.4 to 17.6 +/- 2.0 mmHg; P = 0.01) as compared with the 0.02 microg kg(-1) h(-1) dose (4.7 +/- 0.7 to 7.3 +/- 0.4 mmHg; P = NS). The peak pressure of pyloric phasic pressure waves was 153 +/- 28.4 mmHg and their frequency was 4.9 +/- 1.1 contractions min(-1). CONCLUSIONS: CCK-octapeptide elicits both tonic and phasic activity of the pyloric sphincter. The contractile response to a dose of 0.06 mug kg(-1) h(-1) is greater than the response to 0.02 mug kg(-1) h(-1).

A retrospective review of enteroclysis in patients with obscure gastrointestinal bleeding and chronic abdominal pain of undetermined etiology.

Our purpose was to determine the diagnostic utility of enteroclysis in the evaluation of obscure gastrointestinal bleeding and abdominal pain of unknown etiology. This is a retrospective review of 97 consecutive patients (mean age, 54.1+/-17.5 [SD] years; 49 male and 48 female) who underwent enteroclysis at Temple University Hospital from January 1994 to October 2001 for the evaluation of obscure GI bleeding or chronic abdominal pain of undetermined etiology. Prior to enteroclysis all patients had an EGD and colonoscopy, which were nondiagnostic for their symptoms. Sixty-three patients (64.9%) had enteroscopy performed prior to enteroclysis that was also negative. Enteroclysis results were defined as positive based on anatomical or functional abnormalities. Analysis of the data included the percentage yield of positive exams, the percentage of positive results per symptom category, and the percentage of patients with a change in clinical management based on positive enteroclysis results. Ninety-seven patients underwent enteroclysis. The indications for enteroclysis were obscure GI bleeding in 67 patients (69.1%) and chronic abdominal pain in 30 patients (30.9%). The number of positive exams was 19 (19.6%). Fourteen of the 67 patients with the indication of GI bleeding had a positive exam (21%), while 5 of the 30 patients with chronic abdominal pain had a positive result (16.7%). There was a change in clinical management due to the enteroclysis results in 10 patients: 7 patients with GI bleeding (10%) and 3 patients with chronic abdominal pain (10%). Positive enteroclysis findings included adhesions (7), filling defects and masses (5), strictures (2), small bowel diverticulosis (1), mucosal abnormalities (3), and a motility disorder (1). The overall positive yield for enteroclysis was 19.6%, with a yield of 16.7% for chronic abdominal pain and 21% for gastrointestinal bleeding. Enteroclysis results changed the clinical management in approximately 10% of the patients.