The connection between the gut microbiota and the aetiology of obesity and cardiometabolic disorders is increasingly being recognized by clinicians. Our gut microbiota might affect the cardiometabolic phenotype by fermenting indigestible dietary components and thereby producing short-chain fatty acids (SCFA). These SCFA are not only of importance in gut health and as signalling molecules, but might also enter the systemic circulation and directly affect metabolism or the function of peripheral tissues. In this Review, we discuss the effects of three SCFA (acetate, propionate and butyrate) on energy homeostasis and metabolism, as well as how these SCFA can beneficially modulate adipose tissue, skeletal muscle and liver tissue function. As a result, these SCFA contribute to improved glucose homeostasis and insulin sensitivity. Furthermore, we also summarize the increasing evidence for a potential role of SCFA as metabolic targets to prevent and counteract obesity and its associated disorders in glucose metabolism and insulin resistance. However, most data are derived from animal and in vitro studies, and consequently the importance of SCFA and differential SCFA availability in human energy and substrate metabolism remains to be fully established. Well-controlled human intervention studies investigating the role of SCFA on cardiometabolic health are, therefore, eagerly awaited.

Short-chain Fatty Acids in Control of Body Weight and Insulin Sensitivity

Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved.

Gut microbial metabolites in obesity, NAFLD and T2DM.

Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults.

The human gut harbors >100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia-associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms.

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The Gut Microbiome, Kidney Disease, and Targeted Interventions

Dietary fiber (DF) is deemed to be a key component in healthy eating. DF is not a static collection of undigestible plant materials that pass untouched or unencumbered through the gastrointestinal (GI) tract; instead, DFs are a vast array of complex saccharide-based molecules that can bind potential nutrients and nutrient precursors to prevent their absorption. Some DFs are fermentable, and the GI tract catabolism leads to the generation of various bioactive materials, such as short-chain fatty acids (SCFAs), that can markedly augment the GI tract biomass and change the composition of the GI tract flora. The health benefits of DFs include the prevention and mitigation of type 2 diabetes mellitus, cardiovascular disease and colon cancer. By modulating food ingestion, digestion, absorption and metabolism, DFs reduce the risk of hyperlipidemia, hypercholesterolemia and hyperglycemia. Emerging research has begun to investigate the role of DFs in immunomodulation. If substantiated, DFs could facilitate many biologic processes, including infection prevention and the improvement of mood and memory. This review describes the accepted physiologic functions of DFs and explores their new potential immune-based actions.

/pdf/the-health-benefits-of-dietary-fiber-beyond-the-usual-2iu7chbt5u.pdf

The health benefits of dietary fiber: Beyond the usual suspects of type 2 diabetes mellitus, cardiovascular disease and colon cancer

The fermentation of dietary fiber in the large intestine and the by-products of this fermentation are thought to protect against colonic diseases. As it is difficult to measure the fermentation of dietary fiber in an intact animal, in vitro techniques have been developed to compare the fermentability of various dietary fibers. The objective of this project was to compare short chain fatty acid (SCFA) production with different fibers in an in vitro fermentation model. A wide range of commercially available dietary fiber sources was compared for SCFA production. Fibers were fermented with a fecal innoculum for 0, 2, 4, 8, 12, and 24 hours. SCFAs were measured by gas chromatography. SCFA production varied among the fiber sources. Hydrolyzed guar gum and galactomannan produced the greatest amounts of total SCFAs. Butyrate production was higher with the fiber sources than the glucose control. Acetate production was less for psyllium than the other fibers. Thus, different dietary fiber sources are more readily ...

http://www.protocol-online.org/forums/uploads/monthly_09_2011/msg-6644-0-02237000-1315399909.ipb

Comparison of Different Fibers for In Vitro Production of Short Chain Fatty Acids by Intestinal Microflora

ObjectiveFunctional endoscopic sinus surgery (FESS) provides symptomatic relief of sinus disease in patients with cystic fibrosis (CF), but it is unclear whether it has beneficial effects on lung d

Effect of endoscopic sinus surgery on pulmonary status of adults with cystic fibrosis.

Objective. Functional endoscopic sinus surgery (FESS) pro- vides symptomatic relief of sinus disease in patients with cystic fibrosis (CF), but it is unclear whether it has beneficial effects on lung disease in this population. This study assessed the effect of FESS on the respiratory status of adult patients with CF. Study Design. Retrospective chart review. Setting. Tertiary medical center. Subjects. Thirty-two adult patients with CF who underwent 45 operative cases. Methods. Clinical information retrieved for the 12-month periods preceding and following to determine the effect of FESS on the rate of decline in lung function, as well as intra- venous antibiotic use and hospitalization for pulmonary exacerbation. Results. The rate of decline in forced expiratory volume in 1 second and forced vital capacity was not significantly different in the 12 months before and after FESS. Functional endoscopic sinus surgery did not reduce days hospitalized or days on intra- venous antibiotics for a respiratory exacerbation in the pre- vs postoperative period. Limiting the analysis to the 30 surgeries that were performed in patients with concomitant respiratory symptoms (ie, excluding the 15 surgeries performed for sinus symptoms alone) did not significantly alter the results. Covariates of importance in CF, including CFTR genotype, gender, or microbiology, did not affect the study results. Conclusion. These results did not demonstrate an effect of FESS on progression of lung disease in patients with CF, but further research is needed because low statistical power has made some of the negative findings inconclusive.

Effect of Endoscopic Sinus Surgery on Pulmonary Status of Adults with Cystic

We are currently in the midst of an epidemic of deaths caused by the misuse of prescription medications. Opioids, benzodiazepines, and stimulants are among the most frequently misused controlled substances and are integral to the neurologist's armamentarium. Thus, the decision to prescribe a controlled substance and how to mitigate the associated risks of their misuse is often vexing to the clinician. This installment in the "Clinical Challenge" series provides a basic narrative overview of the epidemiology of prescription drug misuse, a summary of each of the major classes of misused drugs, and clinical recommendations regarding screening for misuse and reducing the risks associated with prescribing controlled substances.

Anne M. Pylkas

Papers

Comparison of Different Fibers for In Vitro Production of Short Chain Fatty Acids by Intestinal Microflora

Effect of endoscopic sinus surgery on pulmonary status of adults with cystic fibrosis.

Effect of Endoscopic Sinus Surgery on Pulmonary Status of Adults with Cystic

Prescribing controlled substances during a prescription drug epidemic