Experimental Capacity of Human Fecal Microbiota to Degrade Fiber and Produce Short-Chain Fatty Acids Is Associated with Diet Quality and Anthropometric Parameters.

BACKGROUND: Short-chain fatty acids (SCFAs) are considered beneficial to human health. The associations between bacterial capacity to produce SCFAs, diet, and health are not fully understood. OBJECTIVE: We aimed to evaluate the capacity of human fecal microbiota to produce SCFAs and to metabolize soluble and insoluble fiber and to study its associations with human diet, anthropometric parameters, and carbohydrate and lipid metabolism. METHODS: A cross-sectional study was carried out with 200 adult participants. Diet was evaluated using food records. Capacity to produce acetate, butyrate, and propionate and to degrade soluble fiber were assessed in an ex vivo experiment where fecal samples were inoculated in a pectin-containing broth. Fecal ß-glucosidase activity was measured to assess potential to degrade insoluble fiber. RESULTS: The main dietary determinants of high capacity to metabolize fiber were high intake of vegetables, fruits, nuts, and seeds. After adjusting analyses for confounders, glucose and lipid parameters were not significantly associated with any of the studied microbial capacities, but the capacity to produce propionic acid was significantly associated with hip circumference (ß = -0.018, P = 0.044), which was seen especially in people eating healthy. CONCLUSIONS: We confirmed that high intake of fiber-rich products is positively associated with the capacity of fecal microbiota to degrade soluble and insoluble dietary fiber and that people eating healthy food might benefit from enhanced microbial capacity to produce propionic acid.

RNA sequencing reveals niche gene expression effects of beta-hydroxybutyrate in primary myotubes.

Various forms of fasting and ketogenic diet have shown promise in (pre-)clinical studies to normalize body weight, improve metabolic health, and protect against disease. Recent studies suggest that ß-hydroxybutyrate (ßOHB), a fasting-characteristic ketone body, potentially acts as a signaling molecule mediating its beneficial effects via histone deacetylase inhibition. Here, we have investigated whether ßOHB, in comparison to the well-established histone deacetylase inhibitor butyrate, influences cellular differentiation and gene expression. In various cell lines and primary cell types, millimolar concentrations of ßOHB did not alter differentiation in vitro, as determined by gene expression and histological assessment, whereas equimolar concentrations of butyrate consistently impaired differentiation. RNA sequencing revealed that unlike butyrate, ßOHB minimally impacted gene expression in primary adipocytes, macrophages, and hepatocytes. However, in myocytes, ßOHB up-regulated genes involved in the TCA cycle and oxidative phosphorylation, while down-regulating genes belonging to cytokine and chemokine signal transduction. Overall, our data do not support the notion that ßOHB serves as a powerful signaling molecule regulating gene expression but suggest that ßOHB may act as a niche signaling molecule in myocytes.

Using naso- and oro-intestinal catheters in physiological research for intestinal delivery and sampling in vivo: practical and technical aspects to be considered.

Intestinal catheters have been used for decades in human nutrition, physiology, pharmacokinetics, and gut microbiome research, facilitating the delivery of compounds directly into the intestinal lumen or the aspiration of intestinal fluids in human subjects. Such research provides insights about (local) dynamic metabolic and other intestinal luminal processes, but working with catheters might pose challenges to biomedical researchers and clinicians. Here, we provide an overview of practical and technical aspects of applying naso- and oro-intestinal catheters for delivery of compounds and sampling luminal fluids from the jejunum, ileum, and colon in vivo. The recent literature was extensively reviewed, and combined with experiences and insights we gained through our own clinical trials. We included 60 studies that involved a total of 720 healthy subjects and 42 patients. Most of the studies investigated multiple intestinal regions (24 studies), followed by studies investigating only the jejunum (21 studies), ileum (13 studies), or colon (2 studies). The ileum and colon used to be relatively inaccessible regions in vivo. Custom-made state-of-the-art catheters are available with numerous options for the design, such as multiple lumina, side holes, and inflatable balloons for catheter progression or isolation of intestinal segments. These allow for multiple controlled sampling and compound delivery options in different intestinal regions. Intestinal catheters were often used for delivery (23 studies), sampling (10 studies), or both (27 studies). Sampling speed decreased with increasing distance from the sampling syringe to the specific intestinal segment (i.e., speed highest in duodenum, lowest in ileum/colon). No serious adverse events were reported in the literature, and a dropout rate of around 10% was found for these types of studies. This review is highly relevant for researchers who are active in various research areas and want to expand their research with the use of intestinal catheters in humans in vivo.

The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice.

BACKGROUND: Obesity and insulin resistance are two major risk factors underlying the metabolic syndrome. The development of these metabolic disorders is frequently studied, but mainly in liver, skeletal muscle, and adipose tissue. To gain more insight in the role of the small intestine in development of obesity and insulin resistance, dietary fat-induced differential gene expression was determined along the longitudinal axis of small intestines of C57BL/6J mice. METHODS: Male C57BL/6J mice were fed a low-fat or a high-fat diet that mimicked the fatty acid composition of a Western-style human diet. After 2, 4 and 8 weeks of diet intervention small intestines were isolated and divided in three equal parts. Differential gene expression was determined in mucosal scrapings using Mouse genome 430 2.0 arrays. RESULTS: The high-fat diet significantly increased body weight and decreased oral glucose tolerance, indicating insulin resistance. Microarray analysis showed that dietary fat had the most pronounced effect on differential gene expression in the middle part of the small intestine. By overrepresentation analysis we found that the most modulated biological processes on a high-fat diet were related to lipid metabolism, cell cycle and inflammation. Our results further indicated that the nuclear receptors Ppars, Lxrs and Fxr play an important regulatory role in the response of the small intestine to the high-fat diet. Next to these more local dietary fat effects, a secretome analysis revealed differential gene expression of secreted proteins, such as Il18, Fgf15, Mif, Igfbp3 and Angptl4. Finally, we linked the fat-induced molecular changes in the small intestine to development of obesity and insulin resistance. CONCLUSION: During dietary fat-induced development of obesity and insulin resistance, we found substantial changes in gene expression in the small intestine, indicating modulations of biological processes, especially related to lipid metabolism. Moreover, we found differential expression of potential signaling molecules that can provoke systemic effects in peripheral organs by influencing their metabolic homeostasis. Many of these fat-modulated genes could be linked to obesity and/or insulin resistance. Together, our data provided various leads for a causal role of the small intestine in the etiology of obesity and/or insulin resistance.