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Concept: Digestive system

355

Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 10(13) bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children.

Concepts: Bacteria, Gut flora, Digestive system, Escherichia coli, Autism, Pervasive developmental disorder, Asperger syndrome, Autism spectrum

263

Microplastics are highly bioavailable to marine organisms, either through direct ingestion, or indirectly by trophic transfer from contaminated prey. The latter has been observed for low-trophic level organisms in laboratory conditions, yet empirical evidence in high trophic-level taxa is lacking. In natura studies face difficulties when dealing with contamination and differentiating between directly and indirectly ingested microplastics. The ethical constraints of subjecting large organisms, such as marine mammals, to laboratory investigations hinder the resolution of these limitations. Here, these issues were resolved by analysing sub-samples of scat from captive grey seals (Halichoerus grypus) and whole digestive tracts of the wild-caught Atlantic mackerel (Scomber scombrus) they are fed upon. An enzymatic digestion protocol was employed to remove excess organic material and facilitate visual detection of synthetic particles without damaging them. Polymer type was confirmed using Fourier-Transform Infrared (FTIR) spectroscopy. Extensive contamination control measures were implemented throughout. Approximately half of scat subsamples (48%; n = 15) and a third of fish (32%; n = 10) contained 1-4 microplastics. Particles were mainly black, clear, red and blue in colour. Mean lengths were 1.5 mm and 2 mm in scats and fish respectively. Ethylene propylene was the most frequently detected polymer type in both. Our findings suggest trophic transfer represents an indirect, yet potentially major, pathway of microplastic ingestion for any species whose feeding ecology involves the consumption of whole prey, including humans.

Concepts: Digestive system, Digestion, Apex predator, Pinniped, Gray Seal, Scombridae, Atlantic mackerel, Mackerel

214

BACKGROUND: The pattern of protein intake following exercise may impact whole-body protein turnover and net protein retention. We determined the effects of different protein feeding strategies on protein metabolism in resistance-trained young men. METHODS: Participants were randomly assigned to ingest either 80g of whey protein as 8x10g every 1.5h (PULSE; n=8), 4x20g every 3h (intermediate, INT; n=7), or 2x40g every 6h (BOLUS; n=8) after an acute bout of bilateral knee extension exercise (4x10 repetitions at 80% maximal strength). Whole-body protein turnover (Q), synthesis (S), breakdown (B), and net balance (NB) were measured throughout 12h of recovery by a bolus ingestion of [15N]glycine with urinary [15N]ammonia enrichment as the collected end-product. RESULTS: PULSE Q rates were greater than BOLUS (~19%, P<0.05) with a trend towards being greater than INT (~9%, P=0.08). Rates of S were 32% and 19% greater and rates of B were 51% and 57% greater for PULSE as compared to INT and BOLUS, respectively (P<0.05), with no difference between INT and BOLUS. There were no statistical differences in NB between groups (P=0.23); however, magnitude-based inferential statistics revealed likely small (mean effect+/-90%CI; 0.59+/-0.87) and moderate (0.80+/-0.91) increases in NB for PULSE and INT compared to BOLUS and possible small increase (0.42+/-1.00) for INT vs. PULSE. CONCLUSION: We conclude that the pattern of ingested protein, and not only the total daily amount, can impact whole-body protein metabolism. Individuals aiming to maximize NB would likely benefit from repeated ingestion of moderate amounts of protein (~20g) at regular intervals (~3h) throughout the day.

Concepts: Metabolism, Nutrition, Eating, Ingestion, Coprophagia, Digestive system, Mouth, Whey protein

187

We present bacterial biogeography as sampled from the human gastrointestinal tract of four healthy subjects. This study generated >32 million paired-end sequences of bacterial 16S rRNA genes (V3 region) representing >95,000 unique operational taxonomic units (OTUs; 97% similarity clusters), with >99% Good’s coverage for all samples. The highest OTU richness and phylogenetic diversity was found in the mouth samples. The microbial communities of multiple biopsy sites within the colon were highly similar within individuals and largely distinct from those in stool. Within an individual, OTU overlap among broad site definitions (mouth, stomach/duodenum, colon and stool) ranged from 32-110 OTUs, 25 of which were common to all individuals and included OTUs affiliated with Faecalibacterium prasnitzii and the TM7 phylum. This first comprehensive characterization of the abundant and rare microflora found along the healthy human digestive tract represents essential groundwork to investigate further how the human microbiome relates to health and disease.

Concepts: Archaea, Microbiology, Ribosomal RNA, Digestive system, 16S ribosomal RNA, Gastroenterology, Human gastrointestinal tract, Digestion

185

It is increasingly perceived that gut host-microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host-microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS.

Concepts: Immune system, Bacteria, Gut flora, Digestive system, Gastroenterology, Irritable bowel syndrome, Flatulence, Probiotic

171

Besides the kidneys, the gastrointestinal tract is the principal organ responsible for sodium homeostasis. For sodium transport across the cell membranes the epithelial sodium channel (ENaC) is of pivotal relevance. The ENaC is mainly regulated by mineralocorticoid receptor mediated actions. The MR activation by endogenous 11β-hydroxy-glucocorticoids is modulated by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Here we present evidence for intestinal segment specific 11β-HSD2 expression and hypothesize that a high salt intake and/or uninephrectomy (UNX) affects colonic 11β-HSD2, MR and ENaC expression. The 11β-HSD2 activity was measured by means of 3H-corticosterone conversion into 3H-11-dehydrocorticosterone in Sprague Dawley rats on a normal and high salt diet. The activity increased steadily from the ileum to the distal colon by a factor of about 3, an observation in line with the relevance of the distal colon for sodium handling. High salt intake diminished mRNA and protein of 11β-HSD2 by about 50% (p<0.001) and reduced the expression of the MR (p<0.01). The functionally relevant ENaC-β and ENaC-γ expression, a measure of mineralocorticoid action, diminished by more than 50% by high salt intake (p<0.001). The observed changes were present in rats with and without UNX. Thus, colonic epithelial cells appear to contribute to the protective armamentarium of the mammalian body against salt overload, a mechanism not modulated by UNX.

Concepts: Protein, Digestive system, Epithelium, Aldosterone, Stomach, Sodium, Laboratory rat, Epithelial sodium channel

170

Treatment with the probiotic bacterium Lactobacillus reuteri has been shown to prevent dextran sodium sulfate (DSS)-induced colitis in rats. This is partly due to reduced P-selectin-dependent leukocyte- and platelet-endothelial cell interactions, however, the mechanism behind this protective effect is still unknown. In the present study a combination of culture dependent and molecular based T-RFLP profiling was used to investigate the influence of L. reuteri on the colonic mucosal barrier of DSS treated rats. It was first demonstrated that the two colonic mucus layers of control animals had different bacterial community composition and that fewer bacteria resided in the firmly adherent layer. During DSS induced colitis, the number of bacteria in the inner firmly adherent mucus layer increased and bacterial composition of the two layers no longer differed. In addition, induction of colitis dramatically altered the microbial composition in both firmly and loosely adherent mucus layers. Despite protecting against colitis, treatment with L. reuteri did not improve the integrity of the mucus layer or prevent distortion of the mucus microbiota caused by DSS. However, L. reuteri decreased the bacterial translocation from the intestine to mesenteric lymph nodes during DSS treatment, which might be an important part of the mechanisms by which L. reuteri ameliorates DSS induced colitis.

Concepts: Archaea, Bacteria, Gut flora, Microbiology, Digestive system, Probiotic, Lactobacillus, Lactobacillus reuteri

169

To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.

Concepts: Bacteria, Digestive system, Large intestine, Intestine, Gastroenterology, Small intestine, Small bowel bacterial overgrowth syndrome, Ileocecal valve

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BACKGROUND: Situs inversus totalis represents an unusual anomaly characterized by a mirror-image transposition of the abdominal and thoracic viscera. It often occurs concomitantly with other disorders that make difficult diagnosis and management of abdominal pathology. The relationship between situs inversus totalis and cancer remains unclear. CASE PRESENTATION: We describe a 33-year old Guinean man with situs inversus totalis who presented with obstructive jaundice. Imaging and endoscopic modalities demonstrated a mass of distal common bile duct which biopsy identified an adenocarcinoma. The patient was successfully treated by cephalic pancreaticoduodenectomy followed by adjuvant chemoradiation and he is doing well without recurrence 8 months after surgery. CONCLUSION: The occurrence of bile duct adenocarcinoma in patient with situs inversus totalis accounts as a rare coincidence. In this setting, when the tumor is resectable, surgical management should be considered without contraindication and must be preceded by a careful preoperative staging.

Concepts: Cancer, Digestive system, Liver, Hepatology, Abdomen, Thorax, Situs inversus, Gallstone

167

Systems capable of residing for prolonged periods of time in the gastric cavity have transformed our ability to diagnose and treat patients. Gastric resident systems for drug delivery, ideally need to be: ingestible, be able to change shape or swell to ensure prolonged gastric residence, have the mechanical integrity to withstand the forces associated with gastrointestinal motility, be triggerable to address any side effects, and be drug loadable and release drug over a prolonged period of time. Materials that have been primarily utilized for these applications have been largely restricted to thermoplastics and thermosets. Here we describe a novel set of materials, triggerable tough hydrogels, meeting all these requirement, supported by evaluation in a large animal model and ultimately demonstrate the potential of triggerable tough hydrogels to serve as prolonged gastric resident drug depots. Triggerable tough hydrogels may be applied in myriad of applications, including bariatric interventions, drug delivery, and tissue engineering.The use of drug delivery systems for the gastrointestinal tract has been faced with a number of drawbacks related to their prolonged use. Here, the authors develop a drug-loaded hydrogel with high strength to withstand long-term gastrointestinal motility and can be triggered to dissolve on demand.

Concepts: Time, Pharmacology, Digestive system, Animal, Human gastrointestinal tract, Abdomen, Period, Digestion