BackgroundThe gastrointestinal motility is affected by gut microbiota and the relationship between them has become a hot topic. However, mechanisms of microbiota in regulating motility have not been well defined. We thus investigated the effect of microbiota depletion by antibiotics on gastrointestinal motility, colonic serotonin levels, and bile acids metabolism.MethodsAfter 4 weeks with antibiotics treatments, gastrointestinal and colon transit, defecation frequency, water content, and other fecal parameters were measured and analyzed in both wild-type and antibiotics-treated mice, respectively. Contractility of smooth muscle, serotonin levels, and bile acids levels in wild-type and antibiotics-treated mice were also analyzed.ResultsAfter antibiotics treatment, the richness and diversity of intestinal microbiota decreased significantly, and the fecal of mice had less output (P < 0.01), more water content (P < 0.01), and longer pellet length (P < 0.01). Antibiotics treatment in mice also resulted in delayed gastrointestinal and colonic motility (P < 0.05), and inhibition of phasic contractions of longitudinal muscle from isolated proximal colon (P < 0.01). In antibiotics-treated mice, serotonin, tryptophan hydroxylase 1, and secondary bile acids levels were decreased.ConclusionGut microbiota play an important role in the regulation of intestinal bile acids and serotonin metabolism, which could probably contribute to the association between gut microbiota and gastrointestinal motility as intermediates.

The recent explosive outbreak of Zika virus (ZIKV) infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive target for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mn2+ and ZIKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATP/Mn2+. The structure of ZIKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZIKV and dengue virus (DENV) apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-016-0293-2) contains supplementary material, which is available to authorized users.

The gut microbiota is involved in various physiological functions, and disturbances in the host-microbiome have been proven to contribute to the dysfunction of gut; however, whether microbiota participates in the pathogenesis of constipation remains unclear. In this study, we extracted and analyzed microbiota in feces from constipated donors who had undergone effective therapy with fecal microbiota transplantation, transplanted microbiota into pseudo-germ-free mice, and measured gut motility. These mice presented with lower pellet frequency and water percentage, smaller pellet size, delayed gastrointestinal transit time, and weaker spontaneous contractions of colonic smooth muscle. To determine the mechanism underlying delayed gut motility, microbial metabolites were measured. Short chain fatty acids and secondary bile acids were decreased in mice receiving microbiota from constipated donors. Moreover, the compositional changes of gut microbiota in constipated patients were identified, including the operational taxonomic unit, and the species richness and α diversity were much greater than those in healthy volunteers. These findings suggest that alterations of the microbiome might affect gut motility via altered microbial-derived metabolites in the development of constipation, and the restoration of disturbed microbiota might improve the clinical phenotype. This study indicates that regulating the intestinal environment may be a novel therapy strategy for constipation.

Fecal microbiota transplantation has been proposed as a therapeutic approach for chronic constipation. This randomized, controlled trial aimed to compare the effects of conventional treatment alone (control) with additional treatment with FMT (intervention) in patients with slow-transit constipation (STC). Adults with STC were randomized to receive intervention or control treatment. The control group received education, behavioral strategies, and oral laxatives. The intervention group was additionally provided 6 days of FMT. The primary endpoint was the clinical cure rate (proportion of patients achieving a mean of ≥ three complete spontaneous bowel movements [CSBMs] per week]. Secondary outcomes and safety parameters were assessed throughout the study. Sixty patients were randomized to either conventional treatment alone (n = 30) or FMT (n = 30) through a nasointestinal tube. There were significant differences between the intervention group and control group in the clinical improvement rate (intention-to-treat [ITT]: 53.3% vs. 20.0%, P = 0.009), clinical cure rate (ITT: 36.7% vs. 13.3%, P = 0.04), mean number of CSBMs per week (ITT: 3.2 ± 1.4 vs. 2.1 ± 1.2, P = 0.001), and the Wexner constipation score (ITT: 8.6 ± 1.5 vs. 12.7 ± 2.5, P < 0.00001). Compared with the control group, the intervention group showed better results in the stool consistency score (ITT: 3.9 vs. 2.4, P < 0.00001) and colonic transit time (ITT: 58.5 vs. 73.6 h, P < 0.00001). The intervention group had more treatment-related adverse events than did the control group (50 vs. 4 cases). FMT was significantly more effective (30% higher cure rate) for treatment of STC than conventional treatment. No serious adverse events were observed.

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BackgroundFecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients.ResultsThree FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P = 0.042 and P = 0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment.ConclusionsPectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC.Trial registrationCurrent Controlled Trial NCT02016469. Registered 10 November 2013Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0869-2) contains supplementary material, which is available to authorized users.

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Background Malnutrition is a common and critical problem that influences outcome in cancer patients. Body composition reflects a patient’s metabolic profile and physiologic reserves, which might be the true determinant of prognosis. In the present study, which aimed to identify valuable new prognostic indicators, we investigated the association between computed tomography–quantified body composition and short-term outcomes after gastrectomy for gastric cancer.MethodsSkeletal muscle index, mean muscle attenuation, and ratio of visceral-to-subcutaneous adipose tissue area (vsr) were calculated from preoperative computed tomography images. Low skeletal muscle index, low mean muscle attenuation, and high vsr were respectively termed “sarcopenia,” “myosteatosis,” and “visceral obesity.” The association of body composition with postoperative complications and serum markers of nutrition and inflammation after radical gastrectomy were analyzed.ResultsThe overall complication rate was significantly higher in the sarcopenia (62.5% vs. 27.3%, p = 0.001) and myosteatosis groups (38.2% vs. 4%, p = 0.002). Patients with visceral obesity had a higher incidence of inflammatory complications (20.3% vs. 6.5%, p = 0.01). Multivariate logistic regression analysis demonstrated that sarcopenia (p = 0.013), myosteatosis (p = 0.017), and low serum retinol-binding protein (p = 0.019) were independent risk factors for overall complications. Compared with control subjects, patients with sarcopenia had lower postoperative levels of serum retinol-binding protein (p = 0.007), and patients with visceral obesity had higher levels of C-reactive protein (p = 0.026).Conclusions Sarcopenia, myosteatosis, and visceral obesity were significantly associated with increased rates of postoperative complications and affected the postoperative nutrition and inflammation status of patients with gastric cancer.