1.Metagenomic Analysis of the Gut Microbiome Reveals Enrichment of Menaquinones (Vitamin K2) Pathway in Diabetes Mellitus
Nihar Ranjan DASH ; Mohammad Tahseen AL BATAINEH
Diabetes & Metabolism Journal 2021;45(1):77-85
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with a high prevalence worldwide, especially among overweight and obese populations. T2DM is multifactorial with several genetic and acquired risk factors that lead to insulin resistance. Mounting evidence indicates that alteration of gut microbiome composition contribute to insulin resistance and inflammation. However, the precise link between T2DM and gut microbiome role and composition remains unknown. We evaluated the metabolic capabilities of the gut microbiome of twelve T2DM and six healthy individuals through shotgun metagenomics using MiSeq platform. We identified no significant differences in the overall taxonomic composition between healthy and T2DM subjects when controlling for differences in diet. However, results showed that T2DM enriched in metabolic pathways involved in menaquinone (vitamin K2) superpathway biosynthesis (PWY-5838) as compared to healthy individuals. Covariance analysis between the bacterial genera and metabolic pathways displaying difference in abundance (analysis of variance The identified differences in metabolic capabilities provide important information that may eventually lead to the development of novel biomarkers and more effective management strategies to treat T2DM.
2.Predictive factors for malignancy in undiagnosed isolated small bowel strictures.
Ujjwal SONIKA ; Sujeet SAHA ; Saurabh KEDIA ; Nihar Ranjan DASH ; Sujoy PAL ; Prasenjit DAS ; Vineet AHUJA ; Peush SAHNI
Intestinal Research 2017;15(4):518-523
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*
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Crohn Disease
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Diagnosis
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Diarrhea
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Humans
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Intestinal Obstruction
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Intestine, Small
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Ischemia
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Medical Records
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Multivariate Analysis
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Retrospective Studies
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Sensitivity and Specificity
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Tuberculosis
3.Serum albumin is the strongest predictor of anti-tumor necrosis factor nonresponse in inflammatory bowel disease in resource-constrained regions lacking therapeutic drug monitoring
Peeyush KUMAR ; Sudheer K. VUYYURU ; Prasenjit DAS ; Bhaskar KANTE ; Mukesh Kumar RANJAN ; David Mathew THOMAS ; Sandeep MUNDHRA ; Pabitra SAHU ; Pratap Mouli VENIGALLA ; Saransh JAIN ; Sandeep GOYAL ; Rithvik GOLLA ; Shubi VIRMANI ; Mukesh K. SINGH ; Karan SACHDEVA ; Raju SHARMA ; Nihar Ranjan DASH ; Govind MAKHARIA ; Saurabh KEDIA ; Vineet AHUJA
Intestinal Research 2023;21(4):460-470
Background/Aims:
Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD).
Methods:
Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies.
Results:
One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively.
Conclusions
Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.