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.

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.

Rates of Diabetes-Related Major Amputations Among Racial and Ethnic Minority Adults Following Medicaid Expansion Under the Patient Protection and Affordable Care Act.

Importance: It is not known whether implementation of Medicaid expansion under the Patient Protection and Affordable Care Act (ACA) was associated with improvements in the outcomes among racial and ethnic minority adults at risk of diabetes-related major amputations. Objective: To explore the association of early Medicaid expansion with outcomes of diabetic foot ulcerations (DFUs). Design, Setting, and Participants: This cohort study included hospitalizations for DFUs among African American, Asian and Pacific Islander, American Indian or Alaska Native, and Hispanic adults as well as adults with another minority racial or ethnic identification aged 20 to 64 years. Data were collected from the State Inpatient Databases for 19 states and the District of Columbia for 2013 to the third quarter of 2015. The analysis was performed on December 4, 2019, and updated on November 9, 2021. Exposures: States were categorized into early-adopter states (expansion by January 2014) and nonadopter states. Main Outcomes and Measures: Poisson regression was performed to examine the associations of state type, time, and their combined association with the proportional changes of major amputation rate per year per 100 000 population. Results: Among the 115 071 hospitalizations among racial and ethnic minority adults with DFUs (64% of sample aged 50 to 64 years; 35%, female; 61%, African American; 25%, Hispanic; 14%, other racial and ethnic minority group), there were 36 829 hospitalizations (32%) for Medicaid beneficiaries and 10 500 hospitalizations (9%) for uninsured patients. Hospitalizations increased 3% (95% CI, 1% to 5%) in early-adopter states and increased 8% (95% CI, 6% to 10%) in nonadopter states after expansion, a significant difference (P for interaction < .001). Although there was no change in the amputation rate (0.08%; 95% CI, -6% to 7%) in early-adopter states after expansion, there was a 9% (95% CI, 3% to 16%) increase in nonadopter states, a significant change (P = .04). For uninsured adults, the amputation rate decreased 33% (95% CI, 10% to 50%) in early-adopter states and did not change (12%; 95% CI, -10% to 38%) in nonadopter states after expansion, a significant difference (P = .006). There was no difference in the change of amputation rate among Medicaid beneficiaries between state types after expansion. Conclusions and Relevance: This study found a relative improvement in the major amputation rate among African American, Hispanic, and other racial and ethnic minority adults in early-expansion states compared with nonexpansion states, which could be because of the recruitment of at-risk uninsured adults into the Medicaid program during the first 2 years of ACA implementation. Future study is required to evaluate the long-term association of Medicaid expansion and the rates of amputation.