Fecal microbiota transplantation for irritable bowel syndrome:An intervention for the 21st century

Irritable bowel syndrome(IBS)affects about 12%of the global population.Although IBS does not develop into a serious disease or increase mortality,it results in a considerable reduction in the quality of life.The etiology of IBS is not known,but the intestinal microbiota appears to play a pivotal role in its pathophysiology.There is no effective treatment for IBS,and so the applied treatments clinically focus on symptom relief.Fecal microbiota transplantation(FMT),an old Chinese treatment,has been applied to IBS patients in seven randomized controlled trials(RCTs).Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs,while there was no effect in the remaining three.Across the seven RCTs there were marked differences in the selection processes for the donor and treated patients,the transplant dose,the route of administration,and the methods used to measure how the patients responded to FMT.The present frontier discusses these differences and proposes:(1)criteria for selecting an effective donor(superdonor);(2)selection criteria for patients that are suitable for FMT;(3)the optimal FMT dose;and(4)the route of transplant administration.FMT appears to be safe,with only mild,self-limiting side effects of abdominal pain,cramping,tenderness,diarrhea,and constipation.Although it is early to speculate about the mechanisms underlying the effects of FMT,the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products(specifically short-chain fatty acids)play an important role in improving the IBS symptoms seen after FMT.FMT appears to be a promising treatment for IBS,but further studies are needed before it can be applied in everyday clinical practice.

Development of innovative tools for investigation of nutrient-gut interaction

The gastrointestinal tract is the key interface between the ingesta and the human body.There is wide recognition that the gastrointestinal response to nutrients or bioactive compounds,particularly the secretion of numerous hormones,is critical to the regulation of appetite,body weight and blood glucose.This concept has led to an increasing focus on“gut-based”strategies for the management of metabolic disorders,including type 2 diabetes and obesity.Understanding the underlying mechanisms and downstream effects of nutrient-gut interactions is fundamental to effective translation of this knowledge to clinical practice.To this end,an array of research tools and platforms have been developed to better understand the mechanisms of gut hormone secretion from enteroendocrine cells.This review discusses the evolution of in vitro and in vivo models and the integration of innovative techniques that will ultimately enable the development of novel therapies for metabolic diseases.

Pancreatic β cell regeneration induced by clinical and preclinical agents

Diabetes,one of the most common chronic diseases in the modern world,has pancreaticβcell deficiency as a major part of its pathophysiological mechanism.Pancreatic regeneration is a potential therapeutic strategy for the recovery ofβcell loss.However,endocrine islets have limited regenerative capacity,especially in adult humans.Almost all hypoglycemic drugs can protectβcells by inhibitingβcell apoptosis and dedifferentiation via correction of hyperglycemia and amelioration of the consequent inflammation and oxidative stress.Several agents,including glucagon-like peptide-1 andγ-aminobutyric acid,have been shown to promoteβcell proliferation,which is considered the main source of the regeneratedβcells in adult rodents,but with less clarity in humans.Pancreatic progenitor cells might exist and be activated under particular circumstances.Artemisinins andγ-aminobutyric acid can induceα-to-βcell conversion,although some disputes exist.Intestinal endocrine progenitors can transdeterminate into insulin-producing cells in the gut after FoxO1 deletion,and pharmacological research into FoxO1 inhibition is ongoing.Other cells,including pancreatic acinar cells,can transdifferentiate intoβcells,and clinical and preclinical strategies are currently underway.In this review,we summarize the clinical and preclinical agents used in different approaches forβcell regeneration and make some suggestions regarding future perspectives for clinical application.

Maternal antibiotic treatment affects offspring gastric sensing for umami taste and ghrelin regulation in the pig

Background:Scarce is knowledge on the process regulating the development of acid secretion,orexigenic signaling,and chemosensing in the stomach of young pigs.Changes of early microbial encounters by suckling pigs can interact with the gut maturation,by the induction of different molecular signaling.Our goal was to assess if the age of offspring and the maternal environment,influenced by sow antibiotic treatment peripartum,could affect gastric morphology and the expression of genes involved in the control of hydrochloric secretion,feed intake,taste,and inflammation in offspring stomach.Methods:84 pigs from sows fed a diet with amoxicillin(on-d10 to+d21 from farrowing,ANT)or without(CON)were sacrificed at d14,d21,d28(weaning)or d42.Samples of oxyntic(OXY),pyloric(PY)and cardiac mucosae close to OXY were collected and parietal and enteroendocrine cells(EECs)were counted.Relative gene expression of a set of 11 key genes(ATP4A,SSTR2,GAST,GHRL,MBOAT4,PCSK1,GNAT1,TAS1R1,TAS1R3,IL8 and TNF)was assessed by qRT-PCR.In addition,40 offspring obtained from the same ANT and CON sows were offered a normal or a fatenriched diet for 4 weeks between 140 and 169 d of age,and then OXY and PY were sampled.Results:The number of parietal and EECs increased with age(P<0.001).ATP4A increased with age(within suckling,P=0.043,post-weaning vs.suckling,P<0.001),SSTR2 increased only after weaning(P<0.001).In OXY,GHRL increased during suckling(P=0.012),and post-weaning as a trend(P=0.088).MBOAT4 tended to increase during suckling(P=0.062).TAS1R1 increased from suckling to post-weaning period(P=0.001)and was lower in ANT offspring(P=0.013).GNAT1 in PY was higher in ANT offspring(P=0.041).Antibiotic treatment of sows peripartum increased expression of GHRL and MBOAT4 in OXY of growing-finishing offspring aged 5 months.Conclusions:Data show that sensing for umami taste and ghrelin regulation can be affected by maternal environment,but the development of acid secretion,orexigenic signaling and taste perception in the stomach are mostly developmentally controlled.