Gopanandan Parthasarathy

Relationship Between Microbiota of the Colonic Mucosa vs Feces and Symptoms, Colonic Transit, and Methane Production in Female Patients With Chronic Constipation.

BACKGROUND & AIMS In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. METHODS Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average, 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). RESULTS Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P < .05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P < .05), and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. CONCLUSIONS After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation.

Temporal Trends in the Incidence and Natural History of Diverticulitis: A Population-Based Study

OBJECTIVES:Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population.METHODS:Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980 to 2007 in Olmsted County, Minnesota, USA.RESULTS:In 1980–1989, the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000–2007 (P<0.001). Incidence increased with age (P<0.001); however, the temporal increase was greater in younger people (P<0.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio (HR) per decade 0.63; 95% confidence interval (CI), 0.59–0.66) and women (HR 0.68; 95% CI, 0.58–0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P<0.001). Age was associated with increased risk of local (odds ratio (OR) 1.27 per decade; 95% CI, 1.04–1.57) and systemic (OR 1.83; 95% CI, 1.20–2.80) complications. Survival after diverticulitis was lower in older people (P<0.001) and men (P<0.001) and worsened over time (P<0.001). The incidence of surgery for diverticulitis did not change from 1980 to 2007.CONCLUSIONS:The incidence of diverticulitis has increased by 50% in 2000–2007 compared with 1990–1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis have less severe disease, more recurrence, and better survival.

Diaphragmatic breathing for rumination syndrome: efficacy and mechanisms of action

While high resolution esophageal manometry combined with impedancometry has demonstrated that gastric pressurizations lead to rumination, the contribution of upper esophageal sphincter (UES) and esophagogastric junction (EGJ) function to rumination is unclear. Behavioral therapy with diaphragmatic breathing (DB) can reduce rumination. We aimed to evaluate the pressures in the stomach, EGJ and UES during rumination and the effects of DB augmented with biofeedback therapy.

High-resolution Anorectal Manometry for Identifying Defecatory Disorders and Rectal Structural Abnormalities in Women

BACKGROUND & AIMS Contrary to conventional wisdom, the rectoanal gradient during evacuation is negative in many healthy people, undermining the utility of anorectal high‐resolution manometry (HRM) for diagnosing defecatory disorders. We aimed to compare HRM and magnetic resonance imaging (MRI) for assessing rectal evacuation and structural abnormalities. METHODS We performed a retrospective analysis of 118 patients (all female; 51 with constipation, 48 with fecal incontinence, and 19 with rectal prolapse; age, 53 ± 1 years) assessed by HRM, the rectal balloon expulsion test (BET), and MRI at Mayo Clinic, Rochester, Minnesota, from February 2011 through March 2013. Thirty healthy asymptomatic women (age, 37 ± 2 years) served as controls. We used principal components analysis of HRM variables to identify rectoanal pressure patterns associated with rectal prolapse and phenotypes of patients with prolapse. RESULTS Compared with patients with normal findings from the rectal BET, patients with an abnormal BET had lower median rectal pressure (36 vs 22 mm Hg, P = .002), a more negative median rectoanal gradient (–6 vs –29 mm Hg, P = .006) during evacuation, and a lower proportion of evacuation on the basis of MRI analysis (median of 40% vs 80%, P < .0001). A score derived from rectal pressure and anorectal descent during evacuation and a patulous anal canal was associated (P = .005) with large rectoceles (3 cm or larger). A principal component (PC) logistic model discriminated between patients with and without prolapse with 96% accuracy. Among patients with prolapse, there were 2 phenotypes, which were characterized by high (PC1) or low (PC2) anal pressures at rest and squeeze along with higher rectal and anal pressures (PC1) or a higher rectoanal gradient during evacuation (PC2). CONCLUSIONS In a retrospective analysis of patients assessed by HRM, measurements of rectal evacuation by anorectal HRM, BET, and MRI were correlated. HRM alone and together with anorectal descent during evacuation may identify rectal prolapse and large rectoceles, respectively, and also identify unique phenotypes of rectal prolapse.

Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders

Acetylcholinesterase inhibitors (ACIs), e.g., neostigmine, are known to increase upper and lower gastrointestinal (GI) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity.

Relationship Between Gastric Emptying and Diurnal Glycemic Control in Type 1 Diabetes Mellitus: A Randomized Trial

Context: In type 1 diabetes (T1D), delayed gastric emptying (GE) may predispose to a mismatch between insulin delivery and glucose absorption. Previous studies evaluated, only partly, the relationship between delayed GE and postprandial, but not diurnal, glycemia. Objective: To assess the relationship between GE disturbances and glycemic control in T1D and the effects of accelerating GE on glycemic control. Design, Setting, and Participants: This was a randomized placebo-controlled trial in 30 patients with T1D on an insulin pump at an academic medical center. Intervention(s): GE was evaluated with a [13C]-Spirulina breath test at baseline (GEbaseline), during intravenous saline or erythromycin (2 or 3 mg/kg; GEiv), and after 7 days of oral erythromycin or placebo (GEoral). Weighed meals were provided throughout the study. Main Outcome Measure(s): These were GE and continuous glucose monitoring (CGM). Results: The baseline glycosylated hemoglobin was 7.6% ± 0.8% (60 ± 8.7 mmol/mol); 12 patients (40%) had delayed GE; faster GE was associated with a greater postprandial CGM-based glucose, but slower GE was not associated with postprandial hypoglycemia (<70 mg/dL). Intravenous (3 mg/kg) but not oral erythromycin accelerated GE. The relationship between GE and glycemia differed between the postprandial periods and the entire day. After adjusting for carbohydrate intake and insulin consumption, faster GE was associated with more hyperglycemia during the postprandial period but lower glucose values across the entire study. Conclusions: In T1D, pharmacologically mediated acceleration of GE increases postprandial CGM-based glucose. In contrast, delayed GE is associated with greater CGM-based glucose values over the entire day.

Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation

Differences in the gut microbiota and breath methane production have been observed in chronic constipation, but the relationship between colonic microbiota, transit, and breath tests remains unclear.

Reproducibility of assessing fecal microbiota in chronic constipation

While limited data suggest that the fecal microbiota in healthy people is stable over time, the intraindividual variability of the fecal microbiota in constipated patients is unknown.

Determinants and clinical impact of pressure drift in manoscan anorectal high resolution manometry system.

Pressure drift (PD), resulting from differences between room and body temperature, reduces the accuracy of pressure measurements with the Manoscan high resolution manometry (HRM) system. Our aims were to assess PD during anorectal HRM.

Aging, Obesity, and the Incidence of Diverticulitis: A Population-Based Study

Objective: To understand why the population‐based incidence of diverticulitis has increased over time, we studied temporal changes in age, body mass index (BMI), and diverticulitis in Olmsted County, Minnesota. Participants and Methods: We compared the BMIs of 2967 patients with diverticulitis and 9795 people without diverticulitis from January 1, 1980, through December 31, 2007. Because BMI is a surrogate for adipose tissue, computed tomographic estimations of abdominal fat content were compared between 381 diverticulitis cases and 381 age‐ and sex‐matched controls. Results: Between 1980 and 2007, the prevalence of obesity increased from 12% to 49% in the population and from 19% to 40% in patients with diverticulitis (P<.001 for both). Temporal trends in age, BMI, and the increased incidence of diverticulitis in people with normal BMI accounted for 48%, 47%, and 20%, respectively, of corresponding trends in diverticulitis. The secular decline in the proportion of people with normal BMI was partly offset by an increased incidence of diverticulitis in such people. In the case‐control study, BMI was greater in cases than in controls (P=.001). However, after incorporating abdominal visceral (odds ratio [OR], 2.4; 95% CI, 1.6‐3.7) and subcutaneous (OR, 2.9; 95% CI, 1.7‐5.2) fat content (both associated with diverticulitis), BMI was associated with lower risk (OR, 0.8; 95% CI, 0.7‐0.8) of diverticulitis. Conclusion: Aging, increasing obesity, and the increased incidence of diverticulitis in people with normal BMI account for the temporal increase in diverticulitis. Rather than BMI per se, increased abdominal visceral and subcutaneous fat are independently associated with diverticulitis. The incidence of diverticulitis, which is among the most common gastrointestinal diagnoses in hospitalized patients, has increased markedly since 2000. This study suggests that aging, increasing obesity, and the increased incidence of diverticulitis in people with normal BMI account for the temporal increase in diverticulitis.