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Background One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed. Results IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 ( P  < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 ( P  = 0.050), IVS-1 + GOS ( P  = 0.022), and GOS ( P  = 0.010), while sucralose excretion was reduced with BB-12 ( P  = 0.002) and GOS ( P  = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed. Conclusion This study demonstrated that “autochthony” of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.

Purpose To examine the dose–response effects of acute glutamine supplementation on markers of gastrointestinal (GI) permeability, damage and, secondary, subjective symptoms of GI discomfort in response to running in the heat. Methods Ten recreationally active males completed a total of four exercise trials; a placebo trial and three glutamine trials at 0.25, 0.5 and 0.9 g kg −1 of fat-free mass (FFM) consumed 2 h before exercise. Each exercise trial consisted of a 60-min treadmill run at 70% of V ˙ O 2max in an environmental chamber set at 30 °C. GI permeability was measured using ratio of lactulose to rhamnose (L:R) in serum. Plasma glutamine and intestinal fatty acid binding protein (I-FABP) concentrations were determined pre and post exercise. Subjective GI symptoms were assessed 45 min and 24 h post-exercise. Results Relative to placebo, L:R was likely lower following 0.25 g kg −1 (mean difference: − 0.023; ± 0.021) and 0.5 g kg −1 (− 0.019; ± 0.019) and very likely following 0.9 g kg − 1 (− 0.034; ± 0.024). GI symptoms were typically low and there was no effect of supplementation. Discussion Acute oral glutamine consumption attenuates GI permeability relative to placebo even at lower doses of 0.25 g kg −1 , although larger doses may be more effective. It remains unclear if this will lead to reductions in GI symptoms. Athletes competing in the heat may, therefore, benefit from acute glutamine supplementation prior to exercise in order to maintain gastrointestinal integrity.

Background/Objectives: Migraine, associated with several gastrointestinal disorders, may result from increased intestinal permeability, allowing endotoxins to enter the bloodstream. We tested whether probiotics could reduce migraine through an effect on intestinal permeability and inflammation. Subjects/Methods: In total, 63 patients were randomly allocated to the probiotic ( n =31) or the placebo group ( n =32). Participants ingested a multispecies probiotic (5x10 9 colony-forming units) or placebo daily for 12 weeks. Migraine was assessed with the Migraine Disability Assessment Scale (MIDAS), the Headache Disability Inventory (HDI) and headache diaries. At baseline and 12 weeks, intestinal permeability was measured with the urinary lactulose/mannitol test and fecal and serum zonulin; inflammation was measured from interleukin (IL) -6, IL-10, tumor necrosis factor-α and C-reactive protein in serum. Results: The MIDAS migraine intensity score significantly decreased in both groups ( P <0.001) and the HDI score significantly decreased in the probiotic group ( P =0.032) and borderline in the placebo group ( P =0.053). In the probiotics group, patients had a median of 6 migraine days in the first month, 4 in the second month ( P =0.002) and 5 in the last month, which was not significantly different from the 5, 4, and 4 days in the placebo group. A ⩾2day reduction in migraine days was seen in 12/31 patients in the probiotics group versus 7/29 in the placebo group (ns). Probiotic use did not significantly affect medication use, intestinal permeability or inflammation compared to placebo. Conclusions: In this study, we could not confirm significant benefit from a multispecies probiotic compared to a placebo on the outcome parameters of migraine and intestinal integrity.

Bristol stool form 1 and 2 is an important predictor of inadequate bowel preparation. To evaluate the efficacy of supplemental preparation in bowel cleansing quality among patients with Bristol stool form 1 and 2, as well as the feasibility of tailored bowel preparation guided by Bristol stool form scale. Patients with Bristol stool form 1 and 2 from 3 Chinese tertiary hospitals randomly received either 2 L PEG-ELP (group A) or 10 mg bisacodyl plus 2 L PEG-ELP (group B); patients with Bristol stool form 3 to 7 received 2 L PEG-ELP (group C) for bowel preparation. The primary endpoint is the rate of adequate bowel reparation for the whole colon. The adequate bowel preparation rate for separate colon segments, the polyp detection rate (PDR), tolerability, acceptability, sleeping quality and compliance were evaluated as secondary endpoints. 700 patients were randomized. In per-protocol analysis, patients in group B attained significantly higher successful preparation rate than group A (88.7% vs. 61.2%, p<0.001) and similar with group C (88.7% vs. 85.0%, p = 0.316). The PDR in group B was significantly higher than group A (43.2% vs. 25.7%, p<0.001). Acceptability was much higher in group B and C. 10 mg bisacodyl plus 2 L PEG-ELP can significantly improve both bowel preparation quality and PDR in patients with Bristol stool form 1 and 2. Bristol stool form scale may be an easy and efficient guide for tailored bowel preparation before colonoscopy.

Very low-carbohydrate diets are often used to promote weight loss, but their effects on bowel health and function are largely unknown. We compared the effects of a very low-carbohydrate, high-fat (LC) diet with a high-carbohydrate, high-fibre, low-fat (HC) diet on indices of bowel health and function. In a parallel study design, ninety-one overweight and obese participants (age 50·6 (sd 7·5) years; BMI 33·7 (sd 4·2) kg/m2) were randomly assigned to either an energy-restricted (about 6-7 MJ, 30 % deficit) planned isoenergetic LC or HC diet for 8 weeks. At baseline and week 8, 24 h urine and faecal collections were obtained and a bowel function questionnaire was completed. Compared with the HC group, there were significant reductions in the LC group for faecal output (21 (sd 145) v. - 61 (sd 147) g), defecation frequency, faecal excretion and concentrations of butyrate ( - 0·5 (sd 10·4) v. - 3·9 (sd 9·7) mmol/l) and total SCFA (1·4 (sd 40·5) v. - 15·8 (sd 43·6) mmol/l) and counts of bifidobacteria (P < 0·05 time x diet interaction, for all). Urinary phenols and p-cresol excretion decreased (P <= 0·003 for time) with no difference between diets (P >= 0·25). Faecal form, pH, ammonia concentration and numbers of coliforms and Escherichia coli did not change with either diet. No differences between the diets were evident for incidences of adverse gastrointestinal symptoms, which suggests that both diets were well tolerated. Under energy-restricted conditions, a short-term LC diet lowered stool weight and had detrimental effects on the concentration and excretion of faecal SCFA compared with an HC diet. This suggests that the long-term consumption of an LC diet may increase the risk of development of gastrointestinal disorders.

Background The zebrafish intestine is a simple tapered tube that is folded into three sections. However, whether the intestine is functionally similar along its length remains unknown. Thus, a systematic structural and functional characterization of the zebrafish intestine is desirable for future studies of the digestive tract and the intestinal biology and development. Results To characterize the structure and function of the adult zebrafish intestine, we divided the intestine into seven roughly equal-length segments, S1-S7, and systematically examined the morphology of the mucosal lining, histology of the epithelium, and molecular signatures from transcriptome analysis. Prominent morphological features are circumferentially-oriented villar ridges in segments S1-S6 and the absence of crypts. Molecular characterization of the transcriptome from each segment shows that segments S1-S5 are very similar while S6 and S7 unique. Gene ontology analyses reveal that S1-S5 express genes whose functions involve metabolism of carbohydrates, transport of lipids and energy generation, while the last two segments display relatively limited function. Based on comparative Gene Set Enrichment Analysis, the first five segments share strong similarity with human and mouse small intestine while S6 shows similarity with human cecum and rectum, and S7 with human rectum. The intestinal tract does not display the anatomical, morphological, and molecular signatures of a stomach and thus we conclude that this organ is absent from the zebrafish digestive system. Conclusions Our genome-wide gene expression data indicate that, despite the lack of crypts, the rostral, mid, and caudal portions of the zebrafish intestine have distinct functions analogous to the mammalian small and large intestine, respectively. Organization of ridge structures represents a unique feature of zebrafish intestine, though they produce similar cross sections to mammalian intestines. Evolutionary lack of stomach, crypts, Paneth cells and submucosal glands has shaped the zebrafish intestine into a simpler but unique organ in vertebrate intestinal biology.

Background: Prebiotics and probiotics exert beneficial effects by modulating gut microbiota and immune system. This study evaluates efficacy and safety of an infant formula containing bovine milk-derived oligosaccharides and Bifidobacterium animalis ssp lactis ( B. lactis ) (CNCM I-3446) on incidence of diarrhea and febrile infections during the first year of life (primary outcome). Methods: Full-term infants receiving Test or Control (without bovine milk-derived oligosaccharide and B. lactis) formulae were enrolled in a multicenter, randomized, controlled, and double-blind trial with a reference breastfeeding group. . Results: 413 infants were assigned between Test ( n = 206) and Control ( n = 207) formula. There was no significant difference for diarrhea and febrile infections incidence between groups at 6 (odds ratio (95% confidence interval) = 0.56 (0.26–1.15), P = 0.096) and 12 mo (odds ratio = 0.66 (0.38–1.14), P = 0.119). Test formula was well tolerated, anthropometrics parameters were not significantly different between groups and aligned with WHO growth standards up to 12 mo. Data from test group showed that gut microbiota pattern, fecal IgA and stool pH were brought to be closer to those of breastfed infants. Conclusion: An infant formula enriched with bovine milk-derived oligosaccharide and B. lactis supports normal infant growth, is well tolerated and improves intestinal health markers. No differences in diarrhea and febrile infection incidence were found in the population studied.

To evaluate the efficacy and mechanistic underpinnings of live tablets in accelerating recovery of intestinal function after gynecologic laparoscopic surgery. A randomized, double-blind, placebo-controlled trial included 115 patients undergoing gynecological laparoscopy, assigned to placebo control (PC, = 39), conventional dose (CD, = 38), and high dose (HD, = 38) groups. Clinical recovery was assessed by timing of first postoperative bowel movement and gastrointestinal adverse reactions. Plasma levels of motilin (MTL) and serotonin (5-HT) were measured using ELISA. Plasma metabolite profiles were analyzed via metabolomics to elucidate treatment-related metabolic pathways. Treatment groups (CD and HD) exhibited significantly reduced time to first postoperative defecation and fewer gastrointestinal adverse reactions compared to PC ( < 0.05), without significant differences between CD and HD groups. Plasma MTL and 5-HT levels significantly increased postoperatively in the treatment groups compared with PC ( < 0.05), without dose-dependent differences. Metabolomics identified 50 and 73 differential metabolites in CD and HD groups post-treatment, respectively, enriched mainly in pathways involving tryptophan, tyrosine, histidine, kynurenine, primary bile acids, and short-chain fatty acids. Live tablets effectively promoted postoperative intestinal recovery in patients undergoing gynecological laparoscopy. The mechanisms likely involve enhanced secretion of MTL and 5-HT, coupled with regulation of key metabolic pathways including tryptophan, tyrosine, kynurenine, histidine metabolism, primary bile acid synthesis, and SCFA metabolism. This study provides insights into probiotics' potential to improve postoperative gastrointestinal outcomes. https://www.chictr.org.cn/, identifier ChiCTR2400079659.

The small intestine is a specialised organ, essential for nutrient digestion and absorption. It is lined with a complex epithelial cell layer. Intestinal epithelial cells can be cultured in three-dimensional (3D) scaffolds as self-organising entities with distinct domains containing stem cells and differentiated cells. Recent developments in bioengineering provide new possibilities for directing the organisation of cells in vitro. In this Perspective, focusing on the small intestine, we discuss how studies at the interface between bioengineering and intestinal biology provide new insights into organ function. Specifically, we focus on engineered biomaterials, complex 3D structures resembling the intestinal architecture, and micro-physiological systems. Maria Antfolk and Kim Jensen discuss how to model intestinal epithelial cell function in the dish and how various physiologically important environmental conditions, for example, extracellular matrix, pressure and flow, can be modelled and how this is applicable to clinical work.

The spatiotemporal structure of the human microbiome 1 , 2 , proteome 3 and metabolome 4 , 5 reflects and determines regional intestinal physiology and may have implications for disease 6 . Yet, little is known about the distribution of microorganisms, their environment and their biochemical activity in the gut because of reliance on stool samples and limited access to only some regions of the gut using endoscopy in fasting or sedated individuals 7 . To address these deficiencies, we developed an ingestible device that collects samples from multiple regions of the human intestinal tract during normal digestion. Collection of 240 intestinal samples from 15 healthy individuals using the device and subsequent multi-omics analyses identified significant differences between bacteria, phages, host proteins and metabolites in the intestines versus stool. Certain microbial taxa were differentially enriched and prophage induction was more prevalent in the intestines than in stool. The host proteome and bile acid profiles varied along the intestines and were highly distinct from those of stool. Correlations between gradients in bile acid concentrations and microbial abundance predicted species that altered the bile acid pool through deconjugation. Furthermore, microbially conjugated bile acid concentrations exhibited amino acid-dependent trends that were not apparent in stool. Overall, non-invasive, longitudinal profiling of microorganisms, proteins and bile acids along the intestinal tract under physiological conditions can help elucidate the roles of the gut microbiome and metabolome in human physiology and disease. Variations in microbial composition, phage induction, antimicrobial resistance genes and bile acid profiles are identified by using an ingestible device for site-specific sampling along the intestines.