Current evidence posits a central role for gut microbiota and the metabolome in the pathogenesis and progression of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been established as a means to manipulate this microbiome safely and sustainably. Several aspects of the technical improvement including pretreatment with antibiotics, use of frozen stool samples as well as short donor-to-recipient time are proposed to improve its response rates. Its efficacy in ulcerative colitis has been proven in clinical trials while data is emerging for Crohn’s disease. This review describes briefly the biology behind FMT, the available evidence for its use in IBD, and the host, recipient and procedural factors which determine the clinical outcomes.

BACKGROUND/AIMS: Patients with small bowel strictures have varied etiologies, including malignancy. Little data are available on the demographic profiles and etiologies of small bowel strictures in patients who undergo surgery because of intestinal obstruction but do not have a definitive pre-operative diagnosis. METHODS: Retrospective data were analyzed for all patients operated between January 2000 and October 2014 for small bowel strictures without mass lesions and a definite diagnosis after imaging and endoscopic examinations. Demographic parameters, imaging, endoscopic, and histological data were extracted from the medical records. Univariate and multivariate analyses were conducted to identify factors that could differentiate between intestinal tuberculosis (ITB) and Crohn's disease (CD) and between malignant and benign strictures. RESULTS: Of the 7,425 reviewed medical records, 89 met the inclusion criteria. The most common site of strictures was the proximal small intestine (41.5%). The most common histological diagnoses in patients with small bowel strictures were ITB (26.9%), CD (23.5%), non-specific strictures (20.2%), malignancy (15.5%), ischemia (10.1%), and other complications (3.4%). Patients with malignant strictures were older than patients with benign etiologies (47.6±15.9 years vs. 37.4±16.4 years, P=0.03) and age >50 years had a specificity for malignant etiology of 80%. Only 7.1% of the patients with malignant strictures had more than 1 stricture and 64% had proximally located strictures. Diarrhea was the only factor that predicted the diagnosis of CD 6.5 (95% confidence interval, 1.10–38.25; P=0.038) compared with the diagnosis of ITB. CONCLUSIONS: Malignancy was the cause of small bowel strictures in approximately 16% patients, especially among older patients with a single stricture in the proximal location. Empirical therapy should be avoided and the threshold for surgical resection is low in these patients.
Constriction, Pathologic* ; Crohn Disease ; Diagnosis ; Diarrhea ; Humans ; Intestinal Obstruction ; Intestine, Small ; Ischemia ; Medical Records ; Multivariate Analysis ; Retrospective Studies ; Sensitivity and Specificity ; Tuberculosis

BACKGROUND/AIMS: Patients with inflammatory bowel disease (IBD) often require immunosuppressive therapy and blood transfusions and therefore are at a high risk of contracting infections due to hepatitis B (HBV) and hepatitis C (HCV) and human immunodeficiency virus (HIV). In the present study, we assessed the prevalence of these infections in patients with IBD. METHODS: This retrospective study included 908 consecutive patients with IBD (ulcerative colitis [UC], n=581; Crohn's disease [CD], n=327) who were receiving care at a tertiary care center. Ninety-five patients with intestinal tuberculosis (ITB) were recruited as disease controls. Prospectively maintained patient databases were reviewed for the prevalence of HBV surface antigen, anti-HCV antibodies, and HIV (enzyme-linked immunosorbent assay method). HCV RNA was examined in patients who tested positive for anti-HCV antibodies. Prevalence data of the study were compared with that of the general Indian population (HBV, 3.7%; HCV, 1%; HIV, 0.3%). RESULTS: The prevalence of HBV, HCV, and HIV was 2.4%, 1.4%, and 0.1%, respectively, in the 908 patients with IBD. Among the 581 patients with UC, 2.2% (12/541) had HBV, 1.7% (9/517) had HCV, and 0.2% (1/499) had HIV. Among the 327 patients with CD, 2.8% (8/288) had HBV, 0.7% (2/273) had HCV, and 0% (0/277) had HIV. One patient with CD had HBV and HCV coinfection. The prevalence of HBV, HCV, and HIV in patients with ITB was 5.9% (4/67), 1.8% (1/57), and 1.2% (1/84), respectively. CONCLUSIONS: The prevalence of HBV, HCV, and HIV in north Indian patients with IBD is similar to the prevalence of these viruses in the general community. Nonetheless, the high risk of flare after immunosuppressive therapy mandates routine screening of patients with IBD for viral markers.
Antigens, Surface ; Biomarkers ; Blood Transfusion ; Coinfection ; Colitis ; Colitis, Ulcerative ; Crohn Disease ; Hepatitis B* ; Hepatitis C Antibodies ; Hepatitis C* ; Hepatitis* ; HIV ; Humans* ; India* ; Inflammatory Bowel Diseases* ; Mass Screening ; Prevalence* ; Prospective Studies ; Retrospective Studies ; RNA ; Tertiary Care Centers ; Tuberculosis

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing, and considering the aging population, this number is set to increase further in the future. The clinical features and natural history of elderly-onset IBD have many similarities with those of IBD in younger patients, but with significant differences including a broader differential diagnosis. The relative lack of data specific to elderly patients with IBD, often stemming from their typical exclusion from clinical trials, has made clinical decision-making somewhat challenging. Treatment decisions in elderly patients with IBD must take into account age-specific concerns such as comorbidities, locomotor and cognitive function, and polypharmacy, to set realistic treatment targets in order to enable personalized treatment and minimize harm. Notwithstanding paucity of clinical data, recent studies have provided valuable insights, which, taken together with information gleaned from previous studies, can broaden our understanding of IBD. These insights may contribute to the development of paradigms for the holistic and, when possible, evidence-based management of this potentially vulnerable population and are the focus of this review.
Aged ; Aging ; Clinical Decision-Making ; Cognition ; Colitis, Ulcerative ; Comorbidity ; Crohn Disease ; Diagnosis, Differential ; Humans ; Incidence ; Inflammatory Bowel Diseases* ; Natural History ; Polypharmacy ; Prevalence ; Vulnerable Populations

BACKGROUND/AIMS: The use of genetic probes for the diagnosis of pulmonary tuberculosis (TB) has been well described. However, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. We therefore assessed the diagnostic utility of the Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) assay, and estimated the prevalence of multidrug-resistant (MDR) TB in the Indian population. METHODS: Of 99 patients recruited, 37 had intestinal TB; two control groups comprised 43 with Crohn's disease (CD) and 19 with irritable bowel syndrome. Colonoscopy was performed before starting any therapy; mucosal biopsies were subjected to histopathology, acid-fast bacilli staining, Lowenstein-Jensen culture, and nucleic acid amplification testing using the Xpert MTB/RIF assay. Patients were followed up for 6 months to confirm the diagnosis and response to therapy. A composite reference standard was used for diagnosis of TB and assessment of the diagnostic utility of the Xpert MTB/RIF assay. RESULTS: Of 37 intestinal TB patients, the Xpert MTB/RIF assay was positive in three of 37 (8.1%), but none had MDR-TB. The sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert MTB/RIF assay was 8.1%, 100%, 100%, and, 64.2%, respectively. CONCLUSIONS: The Xpert MTB/RIF assay has low sensitivity but high specificity for intestinal TB, and may be helpful in endemic tuberculosis areas, when clinicians are faced with difficulty differentiating TB and CD. Based on the Xpert MTB/RIF assay, the prevalence of intestinal MDR-TB is low in the Indian population.
Biopsy ; Colonoscopy ; Crohn Disease ; Diagnosis* ; Humans ; Irritable Bowel Syndrome ; Mycobacterium ; Nucleic Acid Amplification Techniques ; Prevalence ; Sensitivity and Specificity ; Tuberculosis* ; Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary

BACKGROUND/AIMS: Familial occurrence of inflammatory bowel disease (IBD) is well documented. Reports from Western countries have shown a higher familial occurrence of ulcerative colitis (UC) in first- and second-degree relatives than that in the Asian UC population. No data are currently available from the Indian subcontinent in this regard. We present our data on the familial aggregation of UC. METHODS: Records of patients with UC followed at the Inflammatory Bowel Disease Clinic at the All India Institute of Medical Sciences, New Delhi from August 2004 to January 2016 were reviewed. Details regarding the prevalence of family history and characteristics of these patients were recorded. Affected family members were contacted and disease characteristics were noted for assessment of familial aggregation. RESULTS: Of the 2,058 UC patients included in the analysis, a positive family history of IBD was confirmed in 31 patients (1.5%), 24 (77.4%) of whom had only first-degree relatives affected. All the affected relatives had UC and none had Crohn's disease. Among first-degree relatives, siblings were found to have the highest prevalence of IBD (53.3%), followed by parents (26.7%). CONCLUSIONS: The probability of occurrence of IBD in family members of affected North Indian UC patients is lower than that reported in Western populations.
Asian Continental Ancestry Group ; Colitis, Ulcerative* ; Crohn Disease ; Humans ; India ; Inflammatory Bowel Diseases* ; Medical History Taking ; Parents ; Prevalence ; Siblings ; Ulcer*

Abdominal computed tomography (CT) can noninvasively image the entire gastrointestinal tract and assess extraintestinal features that are important in differentiating Crohn's disease (CD) and intestinal tuberculosis (ITB). The present meta-analysis pooled the results of all studies on the role of CT abdomen in differentiating between CD and ITB. We searched PubMed and Embase for all publications in English that analyzed the features differentiating between CD and ITB on abdominal CT. The features included comb sign, necrotic lymph nodes, asymmetric bowel wall thickening, skip lesions, fibrofatty proliferation, mural stratification, ileocaecal area, long segment, and left colonic involvements. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated for all the features. Symmetric receiver operating characteristic curve was plotted for features present in >3 studies. Heterogeneity and publication bias was assessed and sensitivity analysis was performed by excluding studies that compared features on conventional abdominal CT instead of CT enterography (CTE). We included 6 studies (4 CTE, 1 conventional abdominal CT, and 1 CTE+conventional abdominal CT) involving 417 and 195 patients with CD and ITB, respectively. Necrotic lymph nodes had the highest diagnostic accuracy (sensitivity, 23%; specificity, 100%; DOR, 30.2) for ITB diagnosis, and comb sign (sensitivity, 82%; specificity, 81%; DOR, 21.5) followed by skip lesions (sensitivity, 86%; specificity, 74%; DOR, 16.5) had the highest diagnostic accuracy for CD diagnosis. On sensitivity analysis, the diagnostic accuracy of other features excluding asymmetric bowel wall thickening remained similar. Necrotic lymph nodes and comb sign on abdominal CT had the best diagnostic accuracy in differentiating CD and ITB.
Abdomen ; Animals ; Colon ; Comb and Wattles ; Crohn Disease* ; Diagnosis ; Gastrointestinal Tract ; Humans ; Lymph Nodes ; Odds Ratio ; Population Characteristics ; Publication Bias ; ROC Curve ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; Tuberculosis*

BACKGROUND/AIMS: Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB). METHODS: Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1φ marker) and CD163/CD68 (an M2φ marker), and the ratio of M1φ to M2φ was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment. RESULTS: M1φ polarization was more prominent in CD biopsies (P=0.002) than in iTB (P=0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1φ predominance was significant (P=0.001). In iTB, the densities of M1φ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1φ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients. CONCLUSIONS: Proinflammatory M1φ polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD.
Biopsy ; Colon ; Crohn Disease* ; Granuloma ; Humans ; Immune System ; Immunohistochemistry ; Macrophage Activation ; Macrophages* ; Monocytes ; Mucous Membrane ; Pathology ; Phenotype ; Tuberculosis*

BACKGROUND/AIMS: The data on the risk of tuberculosis (TB) reactivation with infliximab (IFX) in patients with inflammatory bowel disease (IBD) from TB endemic countries, like India, is limited. The risk of TB reactivation on IFX and its predictors in patients with IBD was assessed. METHODS: This retrospective review included consecutive patients with IBD who received IFX, and were on follow-up from January 2005 to November 2017. The data was recorded on age/disease duration, indications for IFX, screening for latent tuberculosis (LTB) before IFX, response to IFX, incidence and duration when TB developed after IFX, and type of TB (pulmonary [PTB]/extra-pulmonary [EPTB]/disseminated). RESULTS: Of 69 patients (22 ulcerative colitis/47 Crohn’s disease; mean age, 35.6±14.5 years; 50.7% males; median follow-up duration after IFX, 19 months [interquartile range, 5.5–48.7 months]), primary non-response at 8 weeks and secondary loss of response at 26 and 52 weeks were seen in 14.5%, 6% and 15% patients respectively. Prior to IFX, all patients were screened for LTB, 8 (11.6%) developed active TB (disseminated, 62.5%; EPTB, 25%; PTB, 12.5%) after a median of 19 weeks (interquartile range, 14.0–84.5 weeks) of IFX. Of these 8 patients’ none had LTB, even when 7 of 8 were additionally screened with contrast-enhanced chest tomography. Though not statistically significant, more patients with Crohn’s disease than ulcerative colitis (14.9% vs. 4.5%, P=0.21), and those with past history of TB (25% vs. 9.8%, P=0.21), developed TB. Age, gender, disease duration, or extraintestinal manifestations could not predict TB reactivation. CONCLUSIONS: There is an extremely high rate of TB with IFX in Indian patients with IBD. Current screening techniques are ineffective and it is difficult to predict TB after IFX.
Colitis, Ulcerative ; Crohn Disease ; Follow-Up Studies ; Humans ; Incidence ; India* ; Inflammatory Bowel Diseases* ; Infliximab* ; Interferon-gamma Release Tests ; Latent Tuberculosis ; Male ; Mass Screening* ; Retrospective Studies ; Thorax ; Tuberculosis* ; Ulcer

Background/Aims: Crohn’s disease (CD) and intestinal tuberculosis (ITB) remain “difficult-to-differentiate” diseases. We have previously documented peripheral blood frequency of CD4+CD25+FOXP3+ T-regulatory cells (Treg) as a biomarker to differentiate CD and ITB. We tried to validate these results in a larger cohort of CD and ITB patients. Methods: Seventy treatment naïve patients of CD (n = 23) and ITB (n = 47) (diagnosed by standard criteria) were recruited prospectively from October 2016 to May 2017. Patients with history of antitubercular therapy in the past were excluded. The frequency of Treg cells in peripheral blood was determined by flow cytometry, and compared between CD and ITB patients. Results: Similar to our previous study, frequency of Treg cells in peripheral blood was significantly increased in ITB as compared to CD patients (40.9 [interquartile range, 33–50] vs. 24.9 [interquartile range, 14.4–29.6], P< 0.001). Further, the receiver operating characteristics curve also showed good diagnostic accuracy with an area under the curve (AUC) of 0.77 (95% confidence interval, 0.65–0.89) and a FOXP3+ cutoff value of > 31.3% had a sensitivity and specificity of 83% and 82.6% respectively, to differentiate ITB from CD. Even for the indeterminate cases (n = 33), Treg cell frequency had similar diagnostic accuracy with an AUC of 0.85 (95% confidence interval, 0.68–0.95) and a cutoff of 32.37% had sensitivity and specificity of 87% and 95% respectively, to differentiate ITB from CD. Conclusions The current findings validate that the increased frequency of CD4+CD25+FOXP3+ Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD.