Impact of Plant-Based Dietary Fibers on Metabolic Homeostasis in High-Fat Diet Mice via Alterations in the Gut Microbiota and Metabolites.

BACKGROUND: The gut microbiota contributes to metabolic disease, and diet shapes the gut microbiota, emphasizing the need to better understand how diet impacts metabolic disease via gut microbiota alterations. Fiber intake is linked with improvements in metabolic homeostasis in rodents and humans, which is associated with changes in the gut microbiota. However, dietary fiber is extremely heterogenous, and it is imperative to comprehensively analyze the impact of various plant-based fibers on metabolic homeostasis in an identical setting and compare the impact of alterations in the gut microbiota and bacterially derived metabolites from different fiber sources. OBJECTIVE: The objective of this study is to analyze the impact of different plant-based fibers (pectin, beta-glucan, wheat dextrin, resistant starch, and cellulose as a control) on metabolic homeostasis through alterations in the gut microbiota and its metabolites in high-fat diet (HFD)-fed mice. METHODS: HFD-fed mice were supplemented with 5 different fiber types (pectin, beta-glucan, wheat dextrin, resistant starch, or cellulose as a control) at 10% (w/w) for 18 weeks (n=12/group), measuring body weight, adiposity, indirect calorimetry, glucose tolerance, and the gut microbiota and metabolites. RESULTS: Only beta-glucan supplementation during HFD-feeding decreased adiposity and body weight gain and improved glucose tolerance compared to HFD-cellulose, while all other fibers had no effect. This was associated with increased energy expenditure and locomotor activity in mice compared to HFD-cellulose. All fibers supplemented into a HFD uniquely shifted the intestinal microbiota and cecal short-chain fatty acids, however only beta-glucan supplementation increased cecal butyrate levels. Lastly, all fibers altered the small intestinal microbiota and portal bile acid composition. CONCLUSIONS: These findings demonstrate that beta-glucan consumption is a promising dietary strategy for metabolic disease, possibly via increased energy expenditure through alterations in the gut microbiota and bacterial metabolites in mice.

Differential effects of plant-based flours on metabolic homeostasis and the gut microbiota in high-fat fed rats.

BACKGROUND: The gut microbiome is a salient contributor to the development of obesity, and diet is the greatest modifier of the gut microbiome, which highlights the need to better understand how specific diets alter the gut microbiota to impact metabolic disease. Increased dietary fiber intake shifts the gut microbiome and improves energy and glucose homeostasis. Dietary fibers are found in various plant-based flours which vary in fiber composition. However, the comparative efficacy of specific plant-based flours to improve energy homeostasis and the mechanism by which this occurs is not well characterized. METHODS: In experiment 1, obese rats were fed a high fat diet (HFD) supplemented with four different plant-based flours for 12 weeks. Barley flour (BF), oat bran (OB), wheat bran (WB), and Hi-maize amylose (HMA) were incorporated into the HFD at 5% or 10% total fiber content and were compared to a HFD control. For experiment 2, lean, chow-fed rats were switched to HFD supplemented with 10% WB or BF to determine the preventative efficacy of flour supplementation. RESULTS: In experiment 1, 10% BF and 10% WB reduced body weight and adiposity gain and increased cecal butyrate. Gut microbiota analysis of WB and BF treated rats revealed increases in relative abundance of SCFA-producing bacteria. 10% WB and BF were also efficacious in preventing HFD-induced obesity; 10% WB and BF decreased body weight and adiposity, improved glucose tolerance, and reduced inflammatory markers and lipogenic enzyme expression in liver and adipose tissue. These effects were accompanied by alterations in the gut microbiota including increased relative abundance of Lactobacillus and LachnospiraceaeUCG001, along with increased portal taurodeoxycholic acid (TDCA) in 10% WB and BF rats compared to HFD rats. CONCLUSIONS: Therapeutic and preventative supplementation with 10%, but not 5%, WB or BF improves metabolic homeostasis, which is possibly due to gut microbiome-induced alterations. Specifically, these effects are proposed to be due to increased concentrations of intestinal butyrate and circulating TDCA.

Oligofructose improves small intestinal lipid-sensing mechanisms via alterations to the small intestinal microbiota.

BACKGROUND: Upper small intestinal dietary lipids activate a gut-brain axis regulating energy homeostasis. The prebiotic, oligofructose (OFS) improves body weight and adiposity during metabolic dysregulation but the exact mechanisms remain unknown. This study examines whether alterations to the small intestinal microbiota following OFS treatment improve small intestinal lipid-sensing to regulate food intake in high fat (HF)-fed rats. RESULTS: In rats fed a HF diet for 4 weeks, OFS supplementation decreased food intake and meal size within 2 days, and reduced body weight and adiposity after 6 weeks. Acute (3 day) OFS treatment restored small intestinal lipid-induced satiation during HF-feeding, and was associated with increased small intestinal CD36 expression, portal GLP-1 levels and hindbrain neuronal activation following a small intestinal lipid infusion. Transplant of the small intestinal microbiota from acute OFS treated donors into HF-fed rats also restored lipid-sensing mechanisms to lower food intake. 16S rRNA gene sequencing revealed that both long and short-term OFS altered the small intestinal microbiota, increasing Bifidobacterium relative abundance. Small intestinal administration of Bifidobacterium pseudolongum to HF-fed rats improved small intestinal lipid-sensing to decrease food intake. CONCLUSION: OFS supplementation rapidly modulates the small intestinal gut microbiota, which mediates improvements in small intestinal lipid sensing mechanisms that control food intake to improve energy homeostasis. Video Abstract.

RISING STARS: Endocrine regulation of metabolic homeostasis via the intestine and gut microbiome.

The gastrointestinal system is now considered the largest endocrine organ, highlighting the importance of gut-derived peptides and metabolites in metabolic homeostasis. Gut peptides are secreted from intestinal enteroendocrine cells in response to nutrients, microbial metabolites, and neural and hormonal factors, and they regulate systemic metabolism via multiple mechanisms. While extensive research is focused on the neuroendocrine effects of gut peptides, evidence suggests that several of these hormones act as endocrine signaling molecules with direct effects on the target organ, especially in a therapeutic setting. Additionally, the gut microbiota metabolizes ingested nutrients and fiber to produce compounds that impact host metabolism indirectly, through gut peptide secretion, and directly, acting as endocrine factors. This review will provide an overview of the role of endogenous gut peptides in metabolic homeostasis and disease, as well as the potential endocrine impact of microbial metabolites on host metabolic tissue function.

Oligofructose restores postprandial short-chain fatty acid levels during high-fat feeding.

OBJECTIVE: Obesity is associated with consumption of a Western diet low in dietary fiber, while prebiotics reduce body weight. Fiber induces short-chain fatty acid (SCFA) production, and SCFA administration is beneficial to host metabolic homeostasis. However, the role of endogenous SCFA signaling in the development of obesity is contentious. Therefore, the primary objective of this study is to evaluate the postprandial time course of SCFA production and uptake in healthy (chow-fed), Western diet-fed (high-fat diet [HFD]) obese, and oligofructose-treated HFD-fed (HFD + OFS) rats. METHODS: Male Sprague-Dawley rats were maintained on chow or HFD for 5 weeks, with or without supplementation of 10% OFS for 3 weeks. SCFAs were measured in the ileum, cecum, colon, portal vein, and vena cava at 0, 2, 4, 6, and 8 hours postprandially. RESULTS: Postprandial cecal and portal vein SCFAs were decreased in obese rats compared with lean chow controls, whereas no differences were observed in fasting SCFA concentrations. OFS supplementation increased SCFA levels in the cecum and portal vein during obesity. Butyrate levels were positively associated with portal glucagon-like peptide 1 and adiposity and with Roseburia relative abundance. CONCLUSIONS: The current study demonstrates that obesity is associated with reduced SCFA production, and that OFS supplementation increases SCFA levels. Additionally, postprandial butyrate production appears to be beneficial to host energy homeostasis.

Small intestinal metabolomics analysis reveals differentially regulated metabolite profiles in obese rats and with prebiotic supplementation.

INTRODUCTION: Obesity occurs partly due to consumption of a high-fat, high-sugar and low fiber diet and is associated with an altered gut microbiome. Prebiotic supplementation can reverse obesity and beneficially alter the gut microbiome, evidenced by previous studies in rodents. However, the role of the small intestinal metabolome in obese and prebiotic supplemented rodents has never been investigated. OBJECTIVES: To investigate and compare the small intestinal metabolome of healthy and obese rats, as well as obese rats supplemented with the prebiotic oligofructose (OFS). METHODS: Untargeted metabolomics was performed on small intestinal contents of healthy chow-fed, high fat diet-induced obese, and obese rats supplemented with oligofructose using UPLC-MS/MS. Quantification of enterohepatic bile acids was performed with UPLC-MS to determine specific effects of obesity and fiber supplementation on the bile acid pool composition. RESULTS: The small intestinal metabolome of obese rats was distinct from healthy rats. OFS supplementation did not significantly alter the small intestinal metabolome but did alter levels of several metabolites compared to obese rats, including bile acid metabolites, amino acid metabolites, and metabolites related to the gut microbiota. Further, obese rats had lower total bile acids and increased taurine-conjugated bile acid species in enterohepatic circulation; this effect was reversed with OFS supplementation in high fat-feeding. CONCLUSION: Obesity is associated with a distinct small intestinal metabolome, and OFS supplementation reverses some metabolite levels that were altered in obese rats. Future research into the effects of specific metabolites identified in this study will provide deeper insight into the mechanism of fiber supplementation on improved body weight.

Therapeutic Potential of Various Plant-Based Fibers to Improve Energy Homeostasis via the Gut Microbiota.

Obesity is due in part to increased consumption of a Western diet that is low in dietary fiber. Conversely, an increase in fiber supplementation to a diet can have various beneficial effects on metabolic homeostasis including weight loss and reduced adiposity. Fibers are extremely diverse in source and composition, such as high-amylose maize, ß-glucan, wheat fiber, pectin, inulin-type fructans, and soluble corn fiber. Despite the heterogeneity of dietary fiber, most have been shown to play a role in alleviating obesity-related health issues, mainly by targeting and utilizing the properties of the gut microbiome. Reductions in body weight, adiposity, food intake, and markers of inflammation have all been reported with the consumption of various fibers, making them a promising treatment option for the obesity epidemic. This review will highlight the current findings on different plant-based fibers as a therapeutic dietary supplement to improve energy homeostasis via mechanisms of gut microbiota.

Design and construction of an inexpensive homemade plant growth chamber.

Plant growth chambers produce controlled environments, which are crucial in making reproducible observations in experimental plant biology research. Commercial plant growth chambers can provide precise controls of environmental parameters, such as temperature, humidity, and light cycle, and the capability via complex programming to regulate these environmental parameters. But they are expensive. The high cost of maintaining a controlled growth environment is often a limiting factor when determining experiment size and feasibility. To overcome the limitation of commercial growth chambers, we designed and constructed an inexpensive plant growth chamber with consumer products for a material cost of $2,300. For a comparable growth space, a commercial plant growth chamber could cost $40,000 or more. Our plant growth chamber had outside dimensions of 1.5 m (W) x 1.8 m (D) x 2 m (H), providing a total growth area of 4.5 m2 with 40-cm high clearance. The dimensions of the growth area and height can be flexibly changed. Fluorescent lights with large reflectors provided a relatively spatially uniform photosynthetically active radiation intensity of 140-250 µmoles/m2/sec. A portable air conditioner provided an ample cooling capacity, and a cooling water mister acted as a powerful humidifier. Temperature, relative humidity, and light cycle inside the chamber were controlled via a z-wave home automation system, which allowed the environmental parameters to be monitored and programmed through the internet. In our setting, the temperature was tightly controlled: 22.2°C±0.8°C. The one-hour average relative humidity was maintained at 75%±7% with short spikes up to ±15%. Using the interaction between Arabidopsis and one of its bacterial pathogens as a test experimental system, we demonstrate that experimental results produced in our chamber were highly comparable to those obtained in a commercial growth chamber. In summary, our design of an inexpensive plant growth chamber will tremendously increase research opportunities in experimental plant biology.