Increasing researches have confirmed the relationship between slow-transit constipation and gut microbiota dysbiosis. Many population and animal experiments have identified probiotics as effectors for the relief of constipation symptoms, but the specific mechanism remains unclear. In this intervention study, Lactobacillus rhamnosus strains isolated from five different sources were administered to mice with loperamide-induced constipation, and the impacts of these strains on constipation-related indicators were evaluated. All five strains of L. rhamnosus were found to improve constipation to various degrees. However, contrary to previous studies, the abilities of L. rhamnosus strains to improve constipation symptoms were not associated with the levels of short-chain fatty acids (SCFAs) in the colon. The effects of different strains of L. rhamnosus on constipation relief were associated with different aspects of the GI tract, including gastrointestinal regulatory peptides, neurotransmitters, neurotrophic factors, and gut microbiota. The findings of this study demonstrate that L. rhamnosus strains can alleviate constipation-related symptoms via different pathways independent of SCFAs regulation. This study yields a new perspective for clinical use of probiotics to better improve constipation symptoms, by combining strains with different mechanisms for alleviation of constipation.
BackgroundNoninvasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Recently several exploratory studies showed that circulating level of microRNA is associated with NASH and correlated with disease severity. Although these data were encouraging, the application of circulating microRNA as biomarkers for patient screening and stratification need to be further assessed under well-controlled conditions.ResultsThe expression of circulating microRNAs were profiled in diet-induced NASH progression and regression models to assess the diagnostic and prognostic values and the translatability between preclinical mouse model and men. Since these mice had same genetic background and were housed in the same conditions, there were minimal confounding factors. Histopathological lesions were analyzed at distinct disease progression stages along with microRNA measurement which allows longitudinal assessment of microRNA as NASH biomarkers. Next, differentially expressed microRNAs were identified and validated in an independent cohorts of animals. Thirdly, these microRNAs were examined in a NASH regression model to assess whether they would respond to NASH treatment.MicroRNA profiling in two independent cohorts of animals validated the up-regulation of 6 microRNAs (miR-122, miR-192, miR-21, miR-29a, miR-34a and miR-505) in NASH mice, which was designated as the circulating microRNA signature for NASH. The microRNA signature could accurately distinguish NASH mice from lean mice, and it responded to chow diet treatment in a NASH regression model. To further improve the performance of microRNA-based biomarker, a new composite biomarker was proposed, which consists of miR-192, miR-21, miR-505 and ALT. The new composite biomarker outperformed the microRNA signature in predicting NASH mice which had NAS > 3, and deserves further validations in large scale studies.ConclusionThe present study supported the translation of circulating microRNAs between preclinical models and humans in NASH pathogenesis and progression. The microRNA-based composite biomarker may be used for non-invasive diagnosis, clinical monitoring and assessing treatment response for NASH.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4575-3) contains supplementary material, which is available to authorized users.
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