Deepakshi Srivastava

Irritable bowel syndrome and small intestinal bacterial overgrowth: Meaningful association or unnecessary hype

Irritable bowel syndrome (IBS) is a common condition characterized by abdominal pain or discomfort, bloating, and altered stool form and passage. Small intestinal bacterial overgrowth (SIBO) is a condition in which there is overgrowth of bacteria in small bowel in excess of 10⁵ colony forming units per milliliter on culture of the upper gut aspirate. Frequency of SIBO varied from 4%-78% among patients with IBS and from 1%-40% among controls. Higher frequency in some studies might be due to fallacious criteria [post-lactulose breath-hydrogen rise 20 PPM above basal within 90 min (early-peak)]. Glucose hydrogen breath test (GHBT) has a low sensitivity to diagnose SIBO. Hence, studies based on GHBT might have under-estimated frequency of SIBO. Therefore, it is important to analyze these studies carefully to evaluate whether the reported association between IBS and SIBO is over or under-projected. This review evaluates studies on association between SIBO and IBS, discordance between different studies, their strength and weakness including methodological issues and evidence on therapeutic manipulation of gut flora on symptoms of IBS.

Breath tests in the diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome in comparison with quantitative upper gut aspirate culture.

Background Small intestinal bacterial overgrowth (SIBO) is reported in 4–78% patients with irritable bowel syndrome (IBS). This wide range of percentages might be because of the different techniques and criteria used to define the condition. We studied the utility of early (breath hydrogen increase 20 ppm above basal within 90 min) and double peaks on lactulose and glucose hydrogen breath tests (LHBT and GHBT, respectively) to diagnose SIBO (gold standard: upper gut aspirate culture). We also studied the clinical parameters that are associated with SIBO among them. Methods Overall, 80 patients with IBS (Rome 3) were evaluated for SIBO using aspirate culture, GHBT, and LHBT (with methane). Results A total of 15/80 (19%) patients had SIBO (≥105 CFU/ml) on culture compared with 0/10 historical controls; 4/15 (27%) with and none of 65 without SIBO had positive GHBT (sensitivity 27%, specificity 100%). None of 15 with and one of 65 without SIBO had double peaks on LHBT (sensitivity 0%, specificity 98%); 5/15 (33%) with and 23/65 (35%) without SIBO had an early peak on LHBT (sensitivity 33%, specificity 65%); and 2/15 (13.3%) with and 26/63 (41.3%) without SIBO had high methane on LHBT (sensitivity 13.3%, specificity 58.7%). Patients with SIBO on culture more often had diarrhea [6/15 (40%) vs. 8/65 (12.3%), P=0.011], higher weekly stool frequency [21 (3–28) vs. 14 (4–49), P=0.003], and looser forms [Bristol 5–6, 11/15 (73.3%) vs. 33/65 (50.8%), P=0.116]. Conclusion On the basis of culture, 19% patients with IBS had SIBO. The specificity of GHBT was 100%, but the sensitivity of this test and the diagnostic performances of LHBT and breath methane were all very poor. SIBO was more common in IBS patients with diarrhea than in patients with other bowel habits.

Slow Transit Constipation Associated With Excess Methane Production and Its Improvement Following Rifaximin Therapy: A Case Report

Constipation, a common problem in gastroenterology practice, may result from slow colonic transit. Therapeutic options for slow transit constipations are limited. Excessive methane production by the methanogenic gut flora, which is more often found in patients with constipation, slows colonic transit. Thus, reduction in methane production with antibiotic treatment directed against methanogenic flora of the gut may accelerate colonic transit resulting in improvement in constipation. However, there is not much data to prove this hypothesis. We, therefore, report a patient with slow transit constipation associated with high methane production both in fasting state and after ingestion of glucose, whose constipation improved after treatment with non-absorbable antibiotic, rifaximin, which reduced breath methane values.

A proof-of-concept study showing antibiotics to be more effective in irritable bowel syndrome with than without small-intestinal bacterial overgrowth: a randomized, double-blind, placebo-controlled trial.

Background Antibiotics relieve symptoms in half of the unselected patients with irritable bowel syndrome (IBS); however, their efficacy if selected according to small-intestinal bacterial overgrowth (SIBO) is unknown. Aims The aim of this study was to evaluate (a) symptom resolution among IBS patients with or without SIBO on norfloxacin treatment, and (b) its efficacy in obtaining negative SIBO test results as compared with placebo. Method Eighty IBS patients (Rome III) were evaluated for SIBO by gut aspirate culture. Patients with (≥105 CFU/ml) and those without SIBO were separately randomized (computer-generated stratified) to 800 mg/day norfloxacin for 10 days or placebo. Global symptom score (blindly), Rome III criteria, aspirate culture, and glucose hydrogen breath test (GHBT) were assessed before and 1 month after treatment, and patients were followed up for 6 months. Results Although norfloxacin was more effective at reducing the symptom score at 1 month among patients with compared with those without SIBO [15/80, 19% on culture, four on GHBT too; 6.5 (2–13) vs. 2 (0–10), P=0.01; 8.5 (2–16) vs. 5 (0–12), P<0.001] but not placebo, the scores were comparable at 6 months [3 (1–10) vs. 9 (5–19), P=NS]. Symptoms more often resolved to turn Rome III negative in SIBO patients treated with norfloxacin compared with placebo at 1 month (7/8, 87.5 vs. 0/7, P=0.004); of the other 65 patients, 8/32 (25%) treated with norfloxacin but none of the 33 treated with placebo turned Rome III negative. Patients without SIBO and a colony count of 103–105 CFU/ml responded more than those with a colony count less than 103 CFU/ml. Overall, 15/40 (37.5%) patients responded to norfloxacin. At 6 months, 2/8 (25%) with and 5/32 (15.6%) without SIBO remained Rome III negative following norfloxacin. All 4/8 consenting patients treated with norfloxacin became SIBO negative (two each by culture+GHBT and GHBT alone), but 0/7 patients treated with placebo became SIBO negative. Conclusion Norfloxacin is superior to placebo in relieving symptoms of SIBO-associated IBS.

Tropical Sprue in 2014: the New Face of an Old Disease

Tropical sprue (TS), once known to be a common cause of malabsorption syndrome (MAS) in India and other tropical countries, is believed to be uncommon currently in spite of contrary evidence. Several recent studies from India showed TS to be the commonest cause of sporadic MAS in Indian adults. TS is diagnosed in patients presenting with suggestive clinical presentation, which cannot be explained by another cause of MAS and investigations revealing malabsorption of two unrelated substances, abnormal small-intestinal mucosal histology, which responds to treatment with antibiotics such as tetracycline and folic acid. There is substantial overlap between TS and postinfectious irritable bowel syndrome. There have been several advances in epidemiology, pathogenesis, and diagnosis of TS, hitherto an enigmatic condition.

Small intestinal bacterial overgrowth is common both among patients with alcoholic and idiopathic chronic pancreatitis

BACKGROUND Small intestinal bacterial overgrowth (SIBO) is known to occur in patients with chronic pancreatitis, particularly of alcoholic etiology. There are, however, scanty data on frequency of SIBO in patients with chronic idiopathic pancreatitis and factors associated with its occurrence. METHODS 68 patients with chronic pancreatitis and 74 age and gender-matched healthy subjects (HS) were evaluated for SIBO using glucose hydrogen breath test (GHBT). Persistent rise in breath hydrogen 12 ppm above basal (at least two recordings) was diagnostic of SIBO. RESULT SIBO was diagnosed more often among patients with chronic pancreatitis than controls (10/68 [14.7%] vs. 1/74 controls [1.3%]; p = 0.003). Of 68 patients, 22 (32.3%) had alcoholic and 46 (67.6%) had idiopathic chronic pancreatitis. SIBO was as commonly detected among patients with alcoholic as idiopathic pancreatitis (3/22 [13.6%] vs. 7/46 [15.2%]; p = 0.86). Age, gender, body mass index (BMI), steatorrhoea, pain, analgesic use, pancreatic calcifications and use of pancreatic enzyme supplements had no relationship with the presence of SIBO. Diabetes mellitus tended to be commoner among patients with chronic pancreatitis with than without SIBO (6/10 [60%] vs. 18/58 [31%]; p = 0.07). CONCLUSION SIBO was commoner among patients with chronic pancreatitis, both alcoholic and idiopathic, than HS. Though presence of SIBO among patients with chronic pancreatitis tended to be commoner among those with diabetes mellitus, there was no relationship with age, gender, BMI, steatorrhoea, pain, analgesic use, pancreatic calcifications and use of pancreatic enzyme supplements.

Irritable Bowel Syndrome, Particularly the Constipation-Predominant Form, Involves an Increase in Methanobrevibacter smithii , Which Is Associated with Higher Methane Production

Background/Aims Because Methanobrevibacter smithii produces methane, delaying gut transit, we evaluated M. smithii loads in irritable bowel syndrome (IBS) patients and healthy controls (HC). Methods Quantitative real-time polymerase chain reaction for M. smithii was performed on the feces of 47 IBS patients (Rome III) and 30 HC. On the lactulose hydrogen breath test (LHBT, done for 25 IBS patients), a fasting methane result ≥10 ppm using 10 g of lactulose defined methane-producers. Results Of 47, 20 had constipation (IBS-C), 20 had diarrhea (IBS-D) and seven were not sub-typed. The M. smithii copy number was higher among IBS patients than HC (Log105.4, interquartile range [IQR; 3.2 to 6.3] vs 1.9 [0.0 to 3.4], p<0.001), particularly among IBS-C compared to IBS-D patients (Log106.1 [5.5 to 6.6] vs 3.4 [0.6 to 5.7], p=0.001); the copy number negatively correlated with the stool frequency (R=−0.420, p=0.003). The M. smithii copy number was higher among methane-producers than nonproducers (Log106.4, IQR [5.7 to 7.4] vs 4.1 [1.8 to 5.8], p=0.001). Using a receiver operating characteristic curve, the best cutoff for M. smithii among methane producers was Log106.0 (sensitivity, 64%; specificity, 86%; area under curve [AUC], 0.896). The AUC for breath methane correlated with the M. smithii copy number among methane producers (r=0.74, p=0.008). Abdominal bloating was more common among methane producers (n=9/11 [82%] vs 5/14 [36%], p=0.021). Conclusions Patients with IBS, particularly IBS-C, had higher copy numbers of M. smithii than HC. On LHBT, breath methane levels correlated with M. smithii loads.

Su2055 Genetic Variants Producing Less IL-1ra Are Commoner in Irritable Bowel Syndrome Than Controls and Patients With Small Intestinal Bacterial Overgrowth Have Higher Intestinal Mucosal IL-1 α and β Levels Than Those Without: Evidence for Gut Inflammation

G A A b st ra ct s development of GI symptoms and alteration in intestinal permeability. Methods: In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male soldiers (ages 1923) during combat training and the subsequent rest period using gas chromatographymass spectrometry. Stress was measured using the perceived stress scale-10 item (PSS-10) questionnaire, while incidence and severity of GI symptoms were assessed using the irritable bowel syndrome symptom severity score (IBS-SSS). Whole gut intestinal permeability was evaluated by quantifying the 24h urinary excretion of sucralose as a percentage of the orally administered 1g dose. Results: PSS-10 stress and IBS-SSS scores were higher during the combat-training period than at rest [p<0.05]. The urinary metabotype was clearly distinct from the rest period [partial least squares discriminant analysis (PLSDA) R2X=0.395, R2Y= 0.716, Q2 (cumulative)=0.581], confirming the presence of a unique stress-induced metabotype. Based on PLSDA, differential metabolites related to combat stress were uncovered (e.g. elevated pyroglutamate and fructose; reduced gut microbial metabolites such as hippurate and m-hydroxyphenylacetate) [p<0.05]. The extent of pyroglutamate upregulation exhibited a positive correlation with the increase in IBS-SSS in soldiers during combat-training [r= 0.5, p<0.05]. Additionally, the rise in fructose levels during combat-training was positively correlated with an increase in intestinal permeability [r=0.5, p<0.05]. Conclusion: Protracted and mixed psychological and physical combat-training stress yielded unique metabolic changes that corresponded with the incidence and severity of GI symptoms and alteration in intestinal permeability. Taken together, our data provided new insights into the molecular changes underlying stress-induced GI perturbations which could be exploited for future biomarker research or therapeutic strategies.