Seawater transfer alters the intestinal microbiota profiles of Atlantic salmon (Salmo salar L.)

This study was funded by a BBSRC Eastbio PhD studentship to CED and BBSRC grant BB/M026604/1. The authors wish to thank Ana Rita Sancho Silva for facilitating the sampling for the experiment. Furthermore we would like to express our gratitude to Ian and Alastair Fraser for their support at the SFF fish farms on the Isle of Mull.Peer reviewedPublisher PD

The Brain-Gut-Microbiome Axis.

Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases

Gut microbiota-motility interregulation:Insights from in vivo, ex vivo and in silico studies

The human gastrointestinal tract is home to trillions of microbes. Gut microbial communities have a significant regulatory role in the intestinal physiology, such as gut motility. Microbial effect on gut motility is often evoked by bioactive molecules from various sources, including microbial break down of carbohydrates, fibers or proteins. In turn, gut motility regulates the colonization within the microbial ecosystem. However, the underlying mechanisms of such regulation remain obscure. Deciphering the inter-regulatory mechanisms of the microbiota and bowel function is crucial for the prevention and treatment of gut dysmotility, a comorbidity associated with many diseases. In this review, we present an overview of the current knowledge on the impact of gut microbiota and its products on bowel motility. We discuss the currently available techniques employed to assess the changes in the intestinal motility. Further, we highlight the open challenges, and incorporate biophysical elements of microbes-motility interplay, in an attempt to lay the foundation for describing long-term impacts of microbial metabolite-induced changes in gut motility

Modeling the Fluid Dynamics in a Human Stomach to Gain Insight of Food Digestion

During gastric digestion, food is disintegrated by a complex interaction of chemical and mechanical effects. Although the mechanisms of chemical digestion are usually characterized by using in vitro analysis, the difficulty in reproducing the stomach geometry and motility has prevented a good understanding of the local fluid dynamics of gastric contents. The goal of this study was to use computational fluid dynamics (CFD) to develop a 3-D model of the shape and motility pattern of the stomach wall during digestion, and use it to characterize the fluid dynamics of gastric contents of different viscosities. A geometrical model of an averaged-sized human stomach was created, and its motility was characterized by a series of antral-contraction waves of up to 80% relative occlusion. The flow field within the model (predicted using the software Fluent™) strongly depended on the viscosity of gastric contents. By increasing the viscosity, the formation of the 2 flow patterns commonly regarded as the main mechanisms driving digestion (i.e., the retropulsive jet-like motion and eddy structures) was significantly diminished, while a significant increase of the pressure field was predicted. These results were in good agreement with experimental data previously reported in the literature, and suggest that, contrary to the traditional idea of a rapid and complete homogenization of the meal, gastric contents associated with high viscous meals are poorly mixed. This study illustrates the capability of CFD to provide a unique insight into the fluid dynamics of the gastric contents, and points out its potential to develop a fundamental understanding and modeling of the mechanisms involved in the digestion process

A multi-compartmental mathematical model of the postprandial human stomach : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Anatomy and Physiology at Massey University, Palmerston North, New Zealand

Computational fluid dynamics of the human stomach helps to understand the gastric processes such as trituration, mixing, and transit of digesta. Their outcomes give greater insight into the design of food and orally dosed drug delivery system. Current models of gastric contractile activity are primarily limited to the gastric antrum and assume global values for the various physiological characteristics. This thesis developed a unified compartmental gastric model with correctly informed anatomical and physiological data. The gastric geometry incorporated the actions of multiple compartments, such as the gastric fundus, body, antrum, pyloric canal, proximal duodenal cap, and the small intestinal brake. Lattice-Boltzmann Method (LBM) is used to simulate the fluid dynamics within the stomach. This thesis quantified the effects of transgastric pressure gradient (TGPG) between the fundus and the duodenum, the effect of antral propagating contraction (APC) amplitude, and the viscosity of the gastric contents on gastric flow, mixing, and gastric emptying. The results of this work suggest that TGPG influences gastric emptying where as APCs do not play major role in gastric emptying. Flow rate without TGPG obtained in this work agrees with previous work (Pal et al., 2004); however, it is higher in the presence of a TGPG. Results show that APCs promote recirculation, and the amplitude of APC is vital in this regard. The 'pendulating' flow of gastric content observed in this work is reported previously in duplex sonography experiments (Hausken et al., 1992). This work quantified the gastric shear rates (0.6 - 2.0 /s). This work also suggests that the viscosity of the content influences gastric fluid dynamics. This work is a simplified first step towards a 3D gastric model. Hence, these simulation studies were performed under two simplifications: dimensionality and rheology, i.e., we have assumed a Newtonian fluid flow in 2D gastric geometry. A 3D gastric model with more rheologically realistic fluid to explore the pseudoplastic fluid dynamics within the stomach in the future is recommended

The gut microbiota and immune checkpoint inhibitors.

Although immunotherapy has been remarkably effective across multiple cancer types, there continues to be a significant number of non-responding patients. A possible factor proposed to influence the efficacy of immunotherapies is the gut microbiome. We discuss the results and implications of recent research on the relationship between the gut microbiome, our immune systems, and immune checkpoint inhibitor therapies including anti-CTLA-4 Ab and anti-PD-1 Ab. While the investigations all exhibit interesting results and conclusions, we find little congruence in the specific bacteria that were found favorable for antitumor responses. It is unclear whether the inconsistencies are due to differential approaches in study design (pre-clinical or clinical subjects, anti-CTLA-4 Ab or anti-PD-1 Ab), experimental methods and measurements (metagenomics sequencing and clustering variations) or subject population dynamics (differential cancer types and baseline characteristics). Moreover, we note studies regarding particular bacterial commensals and autoimmune diseases, which challenge findings from these investigations. We conclude that with the current research, clinical investigators can appreciate the critical role of gut microbiota in mediating immunostimulant response. However, prospective research exploring the biochemical mechanisms which commensal bacteria communicate with each other and the immune system is imperative to understand how they can be adjusted properly for higher immunotherapy response