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      • KCI등재

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

        ( Uday C Ghoshal ),( Deepakshi Srivastava ),( Ujjala Ghoshal ),( Ratnakar Shukla ) 대한소화기학회 2016 Gut and Liver Vol.10 No.6

        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 (Log<sub>10</sub>5.4, interquartile range [IQR; 3.2 to 6.3] vs 1.9 [0.0 to 3.4], p<0.001), particularly among IBSC compared to IBS-D patients (Log<sub>10</sub>6.1 [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 Log<sub>10</sub>6.0 (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 IBSC, had higher copy numbers of M. smithii than HC. On LHBT, breath methane levels correlated with M. smithii loads. (Gut Liver 2016;10:932-938)

      • KCI등재

        Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome: A Bridge between Functional Organic Dichotomy

        ( Uday C. Ghoshal ),( Ratnakar Shukla ),( Ujjala Ghoshal ) 대한소화기학회 2017 Gut and Liver Vol.11 No.2

        The pathogenesis of irritable bowel syndrome (IBS), once thought to be largely psychogenic in origin, is now understood to be multifactorial. One of the reasons for this paradigm shift is the realization that gut dysbiosis, including small intestinal bacterial overgrowth (SIBO), causes IBS symptoms. Between 4% and 78% of patients with IBS and 1% and 40% of controls have SIBO; such wide variations in prevalence might result from population differences, IBS diagnostic criteria, and, most importantly, methods to diagnose SIBO. Although quantitative jejunal aspirate culture is considered the gold standard for the diagnosis of SIBO, noninvasive hydrogen breath tests have been popular. Although the glucose hydrogen breath test is highly specific, its sensitivity is low; in contrast, the early-peak criteria in the lactulose hydrogen breath test are highly nonspecific. Female gender, older age, diarrhea-predominant IBS, bloating and flatulence, proton pump inhibitor and narcotic intake, and low hemoglobin are associated with SIBO among IBS patients. Several therapeutic trials targeting gut microbes using antibiotics and probiotics have further demonstrated that not all symptoms in patients with IBS originate in the brain but rather in the gut, providing support for the micro-organic basis of IBS. A recent proof-of-concept study showing the high frequency of symptom improvement in patients with IBS with SIBO further supports this hypothesis.(Gut Liver 2017;11:196-208)

      • KCI등재

        Expression of Toll-like Receptors, Pro-, and Anti-inflammatory Cytokines in Relation to Gut Microbiota in Irritable Bowel Syndrome: The Evidence for Its Micro-organic Basis

        ( Ratnakar Shukla ),( Ujjala Ghoshal ),( Prabhat Ranjan ),( Uday C Ghoshal ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.4

        Background/Aims A Subset of patients with irritable bowel syndrome (IBS) may have mild inflammation due to immune activation. Toll-like receptors (TLRs) and cytokines may cause intestinal inflammation. We studied their expression in relation to gut microbiota. Methods Expression of TLRs and cytokines was assessed in 47 IBS patients (Rome III) and 25 controls using quantitative real-time polymerase chain reaction. Immunohistochemistry was further performed to confirm the expression of TLR-4 and TLR-5. Results Of 47 patients with IBS, 20 had constipation (IBS-C), 20 diarrhea (IBS-D), and 7 unclassified (IBS-U). The mRNA levels of TLR-4 and TLR-5 were up-regulated in IBS patients than controls (P = 0.013 and P < 0.001, respectively). Expression of TLR-4 and TLR-5 at protein level was 4.2-folds and 6.6-folds higher in IBS-D than controls. The mRNA levels of IL-6 (P = 0.003), C-X-C motif chemokine ligand 11 (CXCL-11) (P < 0.001) and C-X-C motif chemokine receptor 3 (CXCR-3) (P < 0.001) were higher among IBS patients than controls. Expression of IL-6 (P = 0.002), CXCL-11 (P < 0.001), and CXCR-3 (P < 0.001) were up-regulated and IL-10 (P = 0.012) was down-regulated in IBS-D patients than controls. Positive correlation was seen between TLR-4 and IL-6 (P = 0.043), CXCR-3, and CXCL-11 (P = 0.047), and IL-6 and CXCR-3 (P = 0.003). Stool frequency per week showed positive correlation with mRNA levels of TLR-4 (P = 0.016) and CXCR-3 (P = 0.005), but inversely correlated with IL-10 (P = 0.002). Copy number of Lactobacillus (P = 0.045) and Bifidobacterium (P = 0.011) showed correlation with IL-10 in IBS-C, while Gram-positive (P = 0.031) and Gram-negative bacteria (P= 0.010) showed correlation with CXCL-11 in IBS-D patients. Conclusions Altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a subset of patients with IBS. (J Neurogastroenterol Motil 2018;24:628-642)

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