Long-term safety and effectiveness of azathioprine in the management of inflammatory bowel disease: A real-world experience.

Background and Aim: Azathioprine (AZA) forms the cornerstone for maintenance of sustained remission in inflammatory bowel disease (IBD). There is apprehension regarding the long-term effectiveness and safety of AZA in IBD. We present our experience with AZA use and outcomes in a cohort of IBD patients followed up over a long period of time. Methods: Records of 507 IBD patients under treatment at a single, tertiary care center in south India between 2013 and 2022 were evaluated retrospectively. Long-term compliance, tolerance, clinical outcome at the point of last follow-up, type and duration to the onset of adverse events, and subsequent amendment to treatment with regard to AZA were analyzed. Results: Of 507 patients with IBD, 320 patients (207 Crohn's disease [CD], 113 ulcerative colitis [UC]) who received AZA were included. The median follow-up was 41 months (interquartile range 15.5-77.5). Total duration of exposure was 1359 patient-years with median usage of 33 months. Of the patients, 26.9% received AZA for >5 years. Mean initiation and maximum doses of AZA were 0.97 and 1.72 mg/kg/day. Among the participants, 20.6% experienced side effects, including myelotoxicity (7.2%) and gastrointestinal intolerance (5.6%). Six patients developed malignancy. Among the side effects, 39.4% of side effects were dose-dependent. Among the patients, 38.1% had relapses requiring pulse corticosteroid therapy, and 16.2% had more than one relapse after commencement of AZA. AZA was continued till the last follow-up in 76.5%. Among the patients, 49.7% (UC 51.3, CD 48.8) attained durable remission without biologics, and 5.3% continued to have active disease. Conclusion: AZA is safe and effective in the long-term in IBD. Effectiveness, tolerance, and compliance with AZA are well sustained beyond 5 years of usage and comparable between UC and CD.

Antibiotic-associated Gut Dysbiosis.

The human gut microbiota plays a crucial role in maintaining overall health. However, the widespread use of antibiotics has raised concerns about its impact on the microbial ecosystem. This review explores the multifaceted relationship between antibiotics and gut dysbiosis, highlighting the mechanisms underlying these interactions and their implications for human health. Antibiotics, while invaluable in treating infections, disrupt the gut microbiota by indiscriminately targeting both harmful and beneficial microorganisms. This disturbance leads to a reduction in microbial diversity, altered metabolite production, and compromised immune responses, resulting in a state referred to as dysbiosis. Broad-spectrum antibiotics tend to induce more severe dysbiosis compared to narrow-spectrum agents. Antibiotic-induced dysbiosis has been linked to the onset and progression of these disorders, emphasizing the far-reaching consequences of microbial imbalance. The review highlights various strategies to mitigate the adverse effects of antibiotics on gut health, like probiotics, fecal microbiota transplantation (FMT), and phage therapy, as promising approaches to restore and maintain a balanced gut microbiota. How to cite this article: Ramakrishna BS, Patankar R. Antibiotic-associated Gut Dysbiosis. J Assoc Physicians India 2023;71(11):62-68.

Distribution of celiac disease predisposing genes HLA-DQ2 and HLA-DQ8 in the native population of southern India.

BACKGROUND: Celiac disease (CD) is an intestinal inflammatory condition caused by the ingestion of gluten peptides in wheat and related grains in individuals carrying HLA-DQ2 and/or HLA-DQ8 genes. In comparison to HLA-DQ8, a higher HLA-DQ2 prevalence is reported in European population where wheat has been the staple food for thousands of years. In non-European population, this pattern of HLA-DQ CD-predisposing gene distribution has not always been found. The aim of this study was to evaluate the HLA-DQ2 and HLA-DQ8 distribution in the native low-gluten consuming southern Indian population. METHODS: Overall, 211 dried blood spots (DBS) were collected from native southern Indian individuals. HLA-DQ characterization and the determination of homozygous/heterozygous status were performed using commercially available HLA-DQ typing kits. RESULTS: Of 211 collected DBS, 88 (42%, 95% CI: 36-48) were positive for HLA-DQ2 and/or HLA-DQ8 heterodimers. Overall, 40 (19%, 95% CI: 14-24) samples typed positive for HLA-DQ2 and 48 (23%, 95% CI: 18-28) typed positive for HLA-DQ8 genotypes. Of 40 HLA-DQ2-positive individuals, only one subject tested homozygous for the DQB1*02 allele. CONCLUSIONS: In the southern Indian native general population, the prevalence of HLA-DQ8 is higher in comparison to HLA-DQ2 prevalence. This finding could be related to the delayed introduction of wheat in the diet of the southern Indian population.

Endoscopic Stone Extraction followed by Laparoscopic Cholecystectomy in Tandem for Concomitant Cholelithiasis and Choledocholithiasis: A Prospective Study.

BACKGROUND: Single-session endoscopic stone extraction (ESE) and laparoscopic cholecystectomy (LC) has the best outcome in managing concomitant cholelithiasis (gallstone disease [GSD]) and choledocholithiasis (common bile duct stone [CBDS]). Traditional rendezvous technique with an intraoperative cholangiogram is associated with various technical (bowel distention, frozen Calot's triangle, limitation of intraoperative cholangiogram and so on) and logistical difficulties (lack of trained personnel and equipment for ESE in the operating room). We modified our approach of ESE-LC (tandem ESE-LC) to study the safety of the approach and overcome these disadvantages of the traditional rendezvous approach. METHODS: A prospective study of patients with GSD and suspected CBDS from January 2017 to December 2019 was conducted. Tandem ESE-LC involves ESE and LC under the same general anaesthesia in a single day, while ESE is performed in the endoscopic suite using carbon dioxide insufflation, a balloon/basket was used for achieving bile duct clearance and the same was confirmed with an occlusion cholangiogram. Patients were then shifted to the operating room for LC. The primary outcome included bile duct clearance and safety of the procedure. RESULTS: Of 56 patients assessed for eligibility, 42 were included in the study (median age: 53 years, 25 [60%] women). Biliary colic was the most common presenting symptom (n = 24, 57%), followed by acute cholecystitis (n = 11, 26%). The median number of stones and stone size was 1 (1-6) and 4 mm (3-10), respectively. All patients had successful bile duct clearance. Stenting was performed in 5 (12%) patients. Intraoperatively, Calot's dissection was difficult and frozen in 10 and 11 patients respectively. The cystic duct was short and wide in 13 (31%) patients. Subtotal cholecystectomy was performed in 6 (14%) patients. The median duration of postprocedural hospital stay was 1 (0-13) day. Three patients had tandem ESE-LC on a day-care basis. One patient had post-endoscopic retrograde cholangiopancretography pancreatitis, and another required percutaneous drainage for gall bladder fossa collection. No patient had retained CBDS at a median follow-up of 18 (3-28) months. CONCLUSION: Tandem ESE-LC is safe and effective method in managing concomitant GSD and CBDS.

Human Leukocyte Antigen DQ (HLA-DQ) genotypes and haplotypes and their association with phenotype in patients with celiac disease in India.

BACKGROUND AND AIM: Human Leukocyte Antigen DQ (HLA-DQ) genotypes play a permissive role in the genesis of celiac disease (CeD). In this case-control study, we used next-generation sequencing to determine HLA-DQA1 and ~DQB1 genotypes and haplotypes associated with CeD in Indian patients. METHODS: HLA-DQA1 and ~DQB1 loci were amplified, using long-range polymerase chain reaction (PCR), from DNA of 259 patients with symptomatic CeD (160 typical and 99 atypical), 45 asymptomatic CeD, 96 potential CeD, and 300 healthy adults. Amplicons were fragmented and sequenced on the Illumina platform, and alleles and haplotypes were assigned by matching against the HLA-international ImMunoGeneTics (IMGT) database. RESULTS: HLA-DQA1*05:01 (odds ratio [OR] 8.39, 95% confidence interval [CI] 5.64-12.47) and HLA-DQB1*02:01 (OR 8.59, 95% CI 5.75-12.83) were the genotypes that showed a risk association with symptomatic CeD. Among the haplotypes, HLA-DQA1*05:01 ~ HLA-DQB1*02:01 (OR 8.56, 95% CI 5.67-13.19) showed a strong risk association with symptomatic CeD. When comparing symptomatic CeD with subclinical forms (asymptomatic and potential) CeD, HLA-DQA1*05:01 ~ HLA-DQB1*02:01 (OR 2.34, 95% CI 1.61-3.43) was significantly associated with risk of symptomatic disease. The strength of association between the HLA-DQA1*05:01 ~ HLA-DQB1*02:01 haplotype and the CeD phenotype showed a gradient in the order typical > atypical > asymptomatic > potential CeD. Genotypes consistent with expression of HLA DQ2 and/or 8 were noted in 128 (80%) typical, 73 atypical (74%), 27 (60%) asymptomatic, and 52 (54%) potential CeD participants. CONCLUSION: HLA-DQA1*05:01 ~ HLA-DQB1*02:01 (haplotype DQ2.5) showed a very strong risk association with symptomatic CeD in Indian patients. The strength of association showed a gradient of increase from potential to typical CeD, coinciding with a phenotypic change in the celiac iceberg.

Assessment of small intestinal bacterial overgrowth in chronic pancreatitis patients using jejunal aspirate culture and glucose hydrogen breath test.

BACKGROUND: A subset of chronic pancreatitis patients respond poorly to pancreatic enzyme replacement therapy. Small intestinal bacterial overgrowth (SIBO) is considered to be one of the major reasons for this poor response. Previous studies have reported a wide range of prevalence of SIBO in patients with chronic pancreatitis. We aimed to assess the prevalence of SIBO in chronic pancreatitis using quantitative jejunal aspirate culture and glucose hydrogen breath test (GHBT). The sensitivity and specificity of GHBT for the diagnosis of SIBO in chronic pancreatitis were also estimated. METHODS: Newly diagnosed chronic pancreatitis patients were recruited into the study. A detailed history and relevant laboratory tests were done. All patients underwent an endoscopy and jejunal fluid aspiration for bacterial cultures and GHBT to detect SIBO. The results of GHBT were compared with jejunal fluid aspirate culture. RESULTS: The jejunal aspirate culture was positive in 18/48 (37.5%) patients while the GHBT showed that 14/48 (29%) patients had SIBO. The sensitivity, specificity, positive and negative predictive value of GHBT in our study was 44.4, 80, 57.14 and 70.59%, respectively. CONCLUSIONS: SIBO is not uncommon in chronic pancreatitis patients. One-third of our study population had SIBO. GHBT has low sensitivity but had high specificity in the diagnosis of SIBO in chronic pancreatitis.

Effect of Native and Acetylated Dietary Resistant Starches on Intestinal Fermentative Capacity of Normal and Stunted Children in Southern India.

The health benefits of dietary amylase resistant starch (RS) arise from intestinal microbial fermentation and generation of short chain fatty acids (SCFA). We compared the intestinal fermentative capability of stunted and nonstunted ('healthy') children in southern India using two types of RS: high amylose maize starch (HAMS) and acetylated HAMS (HAMSA). Twenty children (10 stunted and 10 healthy) aged 2 to 5 years were fed biscuits containing HAMS (10 g/day) for two weeks followed by a 2-week washout and then HAMSA biscuits (10 g/day) for 2 weeks. Fecal samples were collected at 3-4 day intervals and pH and SCFA analyzed. At entry, stunted children had lower SCFA concentrations compared to healthy children. Both types of RS led to a significant decrease in fecal pH and increase in fecal acetate and propionate in both healthy and stunted children. However, while HAMS increased fecal butyrate in both groups of children, HAMSA increased butyrate in healthy but not stunted children. Furthermore, healthy children showed a significantly greater increase than stunted children in both acetate and butyrate when fed either RS. No adverse effects were reported with either RS. Stunted children have impaired capacity to ferment certain types of RS which has implications for choice of RS in formulations aimed at improving microbial function in stunted children.

Frequency of HLA celiac disease risk alleles and haplotypes in healthy adults in Tamil Nadu.

Celiac disease (CeD) occurs only in individuals who are able to express human leukocyte antigens (HLA) DQ2 or DQ8, and these are expressed in nearly a third of healthy people in the West. As the disease is very uncommon in Tamil Nadu, we evaluated the possibility that the relevant genes are infrequent in this population. Four hundred healthy adults without any gastrointestinal abnormalities were recruited from Vellore district of Tamil Nadu. Genomic DNA was extracted from venous blood and amplified by PCR using the allele-specific primers for the following alleles-DQA1*0201, 0301, and 0501 and DQB1*02, 0201, and 0302, which determine the CeD risk haplotypes. Among the 400 healthy adults, the presence of DQ2.5 (DQB1*0201-DQA1*0501) and DQ2.2 (DQB1*02-DQA1*0201) haplotypes was found in 8.25% and 14.25%, respectively. DQ8 (DQB1*0302-DQA1*0301) haplotype was identified in only 3% of healthy individuals. Overall, approximately a quarter of healthy adults in Tamil Nadu had the potential CeD risk haplotypes of HLA DQ2.5, DQ2.2, and DQ8.

A phase 2 randomized controlled trial of oral resistant starch supplements in the prevention of acute radiation proctitis in patients treated for cervical cancer.

BACKGROUND: Radiation induced proctitis is frequently encountered during the radiation therapy of cervical and prostate cancers that causes pain and occasionally with bleeding and may affect the continuity of radiation therapy. AIMS AND OBJECTIVES: The purpose of the study is to look at the benefit of administration of an oral prebiotic amylase resistant starch in reducing the incidence of acute radiation proctitis, a distressing symptom in patients receiving radiation therapy for cancer of the cervix. MATERIAL AND METHODS: The study was conducted between 2011 and 2014 in 104 patients receiving radical chemo-radiotherapy for carcinoma cervix. Patients were randomized in to two arms, one receiving 30 gm of resistant starch and the other digestible starch on a daily basis throughout the course of the external radiotherapy. All patients received standard 4-field box radiation portals, 50 Gy in 25 fractions with 4 cycles of weekly concurrent Cisplatin. At completion of external beam radiotherapy, all patients underwent LDR/HDR brachytherapy. The study was double blinded and allocation was concealed from the investigators. The investigator recorded the radiotherapy related toxicity of the patients according to CTC V 3.0. The incidence and severity of grade 2-4 diarrhoea and proctitis were documented on a weekly basis and compared across the two groups and analyzed. Stool short chain fatty acid concentrations were measured at baseline at 2nd and 4th week and after 6 weeks of completion of radiotherapy in both study placebo arms and reported. The pattern of microbiota in the stool were also estimated in all patients at 4 time points. Two patients who progressed during therapy were not included in the analyses and two patients discontinued the intervention. A per protocol analyses was done. RESULTS: At analysis there were 50 patients in each arm. The severity of clinical proctitis was found to be similar in both groups of patients with 12.2 % of patients experiencing toxicity of grade 2 and above in digestible starch group versus 14.6% in the resistant starch group. Functional proctitis was similarly graded and it was found that 16.3 % patients in digestible starch group experienced toxicity against 10.2 % patients in the resistant starch group. This difference was seen at 4th week and continued in the subsequent weeks till the end of radiation. Both groups had similar reported toxicity at 6 weeks post intervention and similar incidence of grade 2 and above diarrhea. The resistant starch group was found to have 8% incidence as compared to 2% in the other group at the 5th and 6th week. The short chain fatty acid concentrations were not significantly different in the groups at any point. CONCLUSION: The study did not demonstrate a significant benefit in administering resistant starch over and above normal diet to patients receiving pelvic radiotherapy. The reasons may be attributed to concurrent use of chemotherapy and decrease in intestinal probiotics. The use of digestible starch in the control arm may have contributed to lower incidence of the toxicity endpoints as well.

Vitamin D status in Kancheepuram District, Tamil Nadu, India.

BACKGROUND: Vitamin D has multifarious roles in maintenance of health and prevention of disease. The present study was undertaken to assess the vitamin D status of a rural adult south Indian population and to identify its associations with socioeconomic status and cultural practices. METHODS: Between June 2015 and July 2016, 424 healthy adults residing in Kattankulathur block in Tamil Nadu, India, provided venous blood samples and answered questions by personal interview. 25-hydroxy vitamin D was estimated by ELISA. RESULTS: Fifty nine (13.9%) of the 424 participants had 25OHD levels below 12 ng/mL (vitamin D deficient) and 175 (41.3%) had 25OHD levels between 12 to 20 ng/mL (vitamin D insufficiency). In univariate analysis, demographic factors associated with vitamin D status included education, occupation, socioeconomic class, and birthplace; lifestyle factors included sun exposure time, skin surface exposed to sunlight, use of sunscreen, awareness of vitamin D, and consumption of fish; and hygiene related factors included source of drinking water, availability of tap water at home, and closed toilet at home. In ordinal logistic regression, the following variables were found to be independently associated with vitamin D sufficiency: Duration of daily sun exposure below 30 min (Odds ratio 0.31, 95% confidence intervals 0.14-0.71, P = 0.006), sun exposure 30-60 min (OR 0.49, 95% CI 0.30-0.80, P = 0.004), male gender (OR 2.00, 95% CI 1.30-3.09, P = 0.002), higher level of education (OR 0.80, 95% CI 0.69-0.94, P = 0.005), non-consumption of fatty fish (OR 0.48, 95% CI 0.24-0.85, P = 0.035) and presence of closed toilet system at home (OR 0.59, 95% CI 0.37-0.93). CONCLUSION: VDD and VDI are highly prevalent in this rural Indian community. The study identifies socioeconomic and behavior patterns that negatively impact vitamin D sufficiency, thus providing a basis for targeted intervention.

Indian consensus on chronic constipation in adults: A joint position statement of the Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology.

The Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology developed this evidence-based practice guideline for management of chronic constipation. A modified Delphi process was used to develop this consensus containing 29 statements, which were generated by electronic voting iteration as well as face to face meeting and review of the supporting literature primarily from India. These statements include 9 on epidemiology, clinical presentation, and diagnostic criteria; 8 on pathophysiology; and the remaining 12 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The members of the consensus team believe that this would be useful for teaching, clinical practice, and research on chronic constipation in India and in other countries with similar spectrum of the disorders.

Sequential testing with different tissue transglutaminase antibodies, a new approach for diagnosis of celiac disease.

BACKGROUND: The diagnosis of celiac disease (CeD) in clinical practice relies on serological testing for IgA antibodies to human tissue transglutaminase (anti-tTG) which diagnose CeD autoimmunity. We compared three kits for their performance in diagnosis of the disease and evaluated the point prevalence of CeD autoimmunity in a South Indian urban population. METHODS: In the first part of the study, sera from 90 patients with documented CeD and 92 healthy controls were tested for anti-tTG using three different kits. One thousand nine hundred and seventeen healthy adults residing in urban areas of Vellore and Kancheepuram districts were tested for CeD autoimmunity using a sequential two-test strategy. RESULTS: The sensitivity, specificity, false positivity, false negativity, positive predictive value, and negative predictive value for the three assays respectively were as follows: 95.5%, 82.6%, 17.3%, 4.4%, 84.3%, and 95% for the Aeskulisa New Generation Assay; 85.5%, 100%, 0%, 14.4%, 100%, and 87.6% for Quanta Lite; and 71.1%, 100%, 0%, 28.8%, 100%, and 71% for Celiac Microlisa. The ROC curves showed good discrimination for all three ELISAs with an AUC of 0.947, 0.950, and 0.886 for the Aeskulisa, Quanta Lite, and Celiac Microlisa, respectively. Of 1917 (males 908, females 1009) healthy adults, 113 (5.89%) were seropositive for IgA anti-htTG in the Aeskulisa test. Two of the latter tested positive in the Quanta Lite assay and/or the Celiac Microlisa assay. The CeD autoimmunity prevalence in this urban population was 1.0 per thousand (95% confidence interval 0.3 to 3.7 per thousand). CONCLUSION: Sequential testing for anti-tTG using first a highly sensitive assay followed by a very specific assay is a new strategy for screening for CeD in clinical practice.

Faecal microbiota of healthy adults in south India: Comparison of a tribal & a rural population.

BACKGROUND & OBJECTIVES: The relevance of the gut microbiota to human health is increasingly appreciated. The objective of this study was to compare the gut microbiota of a group of adult tribals with that of healthy adult villagers in Tamil Nadu, India. METHODS: Faeces were collected from 10 healthy tribal adults (TAs) in the Jawadhi hills and from 10 healthy villagers [rural adults (RAs)] in Vellore district, Tamil Nadu. DNA was extracted, and 456 bp segments comprising hypervariable regions 3 and 4 of the 16S rRNA gene were amplified, barcoded and 454 sequenced. RESULTS: Totally 227,710 good-quality reads were analyzed. TAs consumed a millets-based diet, ate pork every day, and did not consume milk or milk products. RAs consumed a rice-based diet with meat intake once a week. In both groups, Firmicutes was the most abundant phylum, followed by Proteobacteria, Bacteroidetes and Actinobacteria. The median Firmicutes-to-Bacteroidetes ratio was 34.0 in TA and 92.9 in RA groups. Actinobacteria were significantly low in TA, possibly due to non-consumption of milk. Clostridium constituted the most abundant genus in both groups, but was significantly more abundant in TAs than RAs, while Streptococcus was significantly more abundant in RA (P<0.05). Analyses of genetic distance revealed that the microbiota were distinctly different between TA and RA, and principal component analysis using 550 distinct taxonomically identifiable sequences revealed a clear separation of microbiota composition in the two groups. Phylogenetic analysis of major microbiota indicated clustering of microbial groups at different major branch points for TAs and RAs. INTERPRETATION & CONCLUSIONS: Phylum Firmicutes and genus Clostridium constituted the bulk of the faecal microbiota, while significant differences in composition between the groups were probably due to differences in diet and lifestyle.

Association of ATG16L1 gene haplotype with inflammatory bowel disease in Indians.

Inflammatory bowel disease (IBD) is characterized by multigenic inheritance. Defects in autophagy related genes are considered to show genetic heterogeneity between populations. We evaluated the association of several single nucleotide polymorphisms (SNPs) in the autophagy related 16 like 1 (ATG16L1) gene with IBD in Indians. The ATG16L1 gene was genotyped for ten different SNPs using DNA extracted from peripheral blood of 234 patients with Crohn's disease (CD), 249 patients with ulcerative colitis (UC) and 393 healthy controls The SNPs rs2241880, rs4663396, rs3792106, rs10210302, rs3792109, rs2241877, rs6737398, rs11682898, rs4663402 and rs4663421 were genotyped using the Sequenom MassArray platform. PLINK was used for the association analysis and pairwise linkage disequilibrium (LD) values. Haplotype analysis was done using Haploview. All SNPs were in Hardy Weinberg equilibrium in cases and controls. The G allele at rs6737398 exhibited a protective association with both CD and UC. The T allele at rs4663402 and C allele at rs4663421 were positively associated with CD and UC. The T allele at rs2241877 exhibited protective association with UC only. The AA genotype at rs4663402 and the GG genotype at rs4663421 were protectively associated with both CD and UC. Haplotype analysis revealed that all the SNPs in tight LD (D' = 0.76-1.0) and organized in a single haplotype block. Haplotype D was positively associated with IBD (P = 5.8 x 10-6 for CD and 0.002 for UC). SNPs in ATG16L1 were associated with IBD in Indian patients. The relevance to management of individual patients requires further study.

Drug-development concepts as guides for optimizing clinical trials of supplemental zinc for populations at risk of deficiency or diarrhea.

Studies on the efficacy of zinc supplementation for treatment or prevention of diarrhea have shown an inconsistent effect in populations at risk for zinc deficiency. Unlike drugs, which have no preexisting presence in the body, endogenous zinc must be assessed pharmacokinetically by isotope tracer studies. Although such methods have produced much data, very few studies have estimated the dose and the timing of dosing of zinc supplementation. This review examines drug kinetics used to establish the best dose, the timing of such doses, and the mechanism of action through pharmacodynamic markers and applies them, where possible, to zinc supplements. The findings reveal that little is known, especially in children at highest risk of zinc deficiency. Key data missing to inform proper dosing, whether for treatment of disease or for preventive nutrient supplementation, are noted. Addressing these uncertainties could improve study design, leading to future studies of zinc supplements that might be of greater benefit.

Molecular analysis of the human faecal archaea in a southern Indian population.

Archaea are an important constituent of the human gut microbiota, but there is no information on human gut archaea in an Indian population. In this study, faecal samples were obtained from different age groups (neonatal babies, preschool children, school-going children, adolescents, adults and elderly) of a southern Indian population, and from a tribal population also resident in southern India). 16S rRNA gene sequences specific to Archaea were amplified from pooled faecal DNA in each group, sequenced, and aligned against the NCBI database. Of the 806 adequate sequences in the study, most aligned with 22 known sequences. There were 9 novel sequences in the present study. All sequences were deposited in the GenBank nucleotide sequence database with the following accession numbers: KF607113 - KF607918. Methanobrevibacter was the most prevalent genus among all the age groups accounting for 98% in neonates, 96% in post-weaning, and 100% each in preschool, school and adult population. In the elderly, Methanobrevibacter accounted for 96% and in tribal adults, 99% of the clones belonged to Methanobrevibacter genus. Other genera detected included Caldisphaera, Halobaculum, Methanosphaeraand Thermogymnomonas. Methanobrevibacter smithii predominated in all age groups, accounting for 749 (92.9%) of the 806 sequences. Archaea can be found in the faeces of southern Indian residents immediately after birth. Methanobrevibacter smithii was the dominant faecal archeon in all age groups, with other genera being found at the extremes of age.

Alterations of mucosal microbiota in the colon of patients with inflammatory bowel disease revealed by real time polymerase chain reaction amplification of 16S ribosomal ribonucleic acid.

BACKGROUND & OBJECTIVES: Alterations in microbial communities closely associated with the intestinal mucosa are likely to be important in the pathogenesis of inflammatory bowel disease (IBD). We examined the abundance of specific microbial populations in colonic mucosa of patients with ulcerative colitis (UC), Crohn's disease (CD) and controls using reverse transcription quantitative polymerase chain reaction (RT-qPCR) amplification of 16S ribosomal ribonucleic acid (16S rRNA). METHODS: RNA was extracted from colonic mucosal biopsies of patients with UC (32), CD (28) and patients undergoing screening colonoscopy (controls), and subjected to RT-qPCR using primers targeted at 16S rRNA sequences specific to selected microbial populations. RESULTS: Bacteroides-Prevotella-Porphyromonas group and Enterobacteriaceae were the most abundant mucosal microbiota. Bacteroides and Lactobacillus abundance was greater in UC patients compared with controls or CD. Escherichia coli abundance was increased in UC compared with controls. Clostridium coccoides group and C. leptum group abundances were reduced in CD compared with controls. Microbial population did not differ between diseased and adjacent normal mucosa, or between untreated patients and those already on medical treatment. The Firmicutes to Bacteroidetes ratio was significantly decreased in both UC and CD compared with controls, indicative of a dysbiosis in both conditions. INTERPRETATION & CONCLUSIONS: Dysbiosis appears to be a primary feature in both CD and UC. Microbiome-directed interventions are likely to be appropriate in therapy of IBD.

Intermittent Directly Observed Therapy for Abdominal Tuberculosis: A Multicenter Randomized Controlled Trial Comparing 6 Months Versus 9 Months of Therapy.

BACKGROUND: The duration of treatment of gastrointestinal tuberculosis continues to be a matter of debate. The World Health Organization advocates intermittent directly observed short-course therapy (DOTs), but there is a lack of data of its efficacy in abdominal tuberculosis. We therefore conducted a multicenter randomized controlled trial to compare 6 months and 9 months of antituberculosis therapy using DOTs. METHODS: One hundred ninety-seven patients with abdominal tuberculosis (gastrointestinal, 154; peritoneal, 40; mixed, 3) were randomized to receive 6 months (n = 104) or 9 months (n = 93) of antituberculosis therapy using intermittent directly observed therapy. Patients were followed up 1 year after completion of treatment to assess recurrence. Patients were evaluated for primary endpoint (complete clinical response, partial response, and no response) and secondary endpoint (recurrence of the disease at the end of 1 year of follow-up). RESULTS: Baseline characteristics were similar between the 2 randomized groups. There was no difference between the 6-month group and 9-month group in the complete clinical response rate on per-protocol analysis (91.5% vs 90.8%; P = .88) or intent-to-treat analysis (75% vs 75.8%; P = .89). Only 1 patient in the 9-month group and no patients in the 6-month group had recurrence of disease. Side effects occurred in 21 (21.3%) and 16 (18.2%) patients in the 6-month and 9-month groups, respectively. CONCLUSIONS: There was no difference in efficacy of antituberculosis therapy delivered for either 6 months or 9 months in either gastrointestinal or peritoneal tuberculosis, confirming the efficacy of intermittent directly observed therapy. CLINICAL TRIALS REGISTRATION: NCT01124929.

Indian Society of Gastroenterology consensus statements on Crohn's disease in India.

In 2012, the Indian Society of Gastroenterology's Task Force on Inflammatory Bowel Diseases undertook an exercise to produce consensus statements on Crohn's disease (CD). This consensus, produced through a modified Delphi process, reflects our current recommendations for the diagnosis and management of CD in India. The consensus statements are intended to serve as a reference point for teaching, clinical practice, and research in India.

Protective association of tumor necrosis factor superfamily 15 (TNFSF15) polymorphic haplotype with Ulcerative Colitis and Crohn's disease in an Indian population.

BACKGROUND: Tumor necrosis factor superfamily (TNFSF) proteins are involved in the genesis of inflammatory bowel disease (IBD). We examined the association of seven single nucleotide polymorphisms (SNP) in the TNFSF15 gene with Crohn's disease (CD) and ulcerative colitis (UC) in the Indian population. METHODS: Seven SNPs in the TNFSF15 gene (rs10114470, rs3810936, rs6478108, rs4263839, rs6478109, rs7848647 and rs7869487) were genotyped in 309 CD patients, 330 UC patients and 437 healthy controls using the Sequenom iPLEX MassArray platform. Disease associations were evaluated for allelotypes and for genotypes. RESULTS: The minor T alleles and the TT genotypes of rs10114470 and rs3810936 were significantly protectively associated with both CD and UC. The CC genotype of rs6478108, AA genotype of rs4263839, the AA genotype of rs6478109, the TT genotype of rs7848647 and the CC genotype of rs7869487 were all protectively associated with CD but not with UC. Two haplotype blocks could be discerned, one where SNPs rs10114470 and rs3810936 were in tight LD (D' = 0.8) and the other where rs6478108, rs4263839, rs6478109, rs7848647 and rs7869487 were in tight LD (D' 0.92-1.00). The second block of haplotypes were not associated with CD or with UC. The first block of haplotypes was very significantly associated with both CD and UC. CONCLUSIONS: Strong associations exist between TNFSF15 gene polymorphisms and IBD (both CD and UC) in the Indian population.