Nutrition Knowledge Is Associated With Diet Quality Among US Army Soldiers.

OBJECTIVE: Examine the relationship between nutrition knowledge, diet quality, and eating behavior among active-duty US Army Soldiers. METHODS: Cross-sectional study with data collection in February 2018 via paper surveys during the validation of the Military Eating Behavior Survey. RESULTS: Among 440 US Army Soldiers, nutrition knowledge was positively and significantly associated with diet quality (b = 0.29, P < 0.001). For every 1-point increase in nutrition knowledge, the Healthy Eating Index-2015 score was expected to increase by 0.29 points. Nutrition knowledge was not significantly associated with skipping breakfast (odds ratio, 1.01; 95% confidence interval, 0.98-1.04) or dining out (odds ratio, 1.01; 95% confidence interval, 0.98-1.03). CONCLUSIONS AND IMPLICATIONS: The outcomes of this study warrant further investigation to determine what interventions provide the strongest outcomes for improving nutrition knowledge and diet quality, as well as create and support an environment that enhances healthy behaviors regarding nutrition that lead to improved diet quality among active-duty Soldiers.

Orally Ingested Probiotic, Prebiotic, and Synbiotic Interventions as Countermeasures for Gastrointestinal Tract Infections in Nonelderly Adults: A Systematic Review and Meta-Analysis.

Meta-analyses have not examined the prophylactic use of orally ingested probiotics, prebiotics, and synbiotics for preventing gastrointestinal tract infections (GTIs) of various etiologies in adult populations, despite evidence that these gut microbiota-targeted interventions can be effective in treating certain GTIs. This systematic review and meta-analysis aimed to estimate the effects of prophylactic use of orally ingested probiotics, prebiotics, and synbiotics on GTI incidence, duration, and severity in nonelderly, nonhospitalized adults. CENTRAL, PubMed, Scopus, and Web of Science were searched through January 2022. English-language, peer-reviewed publications of randomized, placebo-controlled studies testing an orally ingested probiotic, prebiotic, or synbiotic intervention of any dose for ≥1 wk in adults who were not hospitalized, immunosuppressed, or taking antibiotics were included. Results were analyzed using random-effects meta-analyses of intention-to-treat (ITT) and complete case (CC) cohorts. Heterogeneity was explored by subgroup meta-analysis and meta-regression. The risk of bias was assessed using the Cochrane risk-of-bias 2 tool. Seventeen publications reporting 20 studies of probiotics (n = 16), prebiotics (n = 3), and synbiotics (n = 1) were identified (n > 6994 subjects). In CC and ITT analyses, risk of experiencing ≥1 GTI was reduced with probiotics (CC analysis-risk ratio: 0.86; 95% CI: 0.73, 1.01) and prebiotics (risk ratio: 0.80; 95% CI: 0.66, 0.98). No effects on GTI duration or severity were observed. Sources of heterogeneity included the study population and number of probiotic strains administered but were often unexplained, and a high risk of bias was observed for most studies. The specific effects of individual probiotic strains and prebiotic types could not be assessed owing to a lack of confirmatory studies. Findings indicated that both orally ingested probiotics and prebiotics, relative to placebo, demonstrated modest benefit for reducing GTI risk in nonelderly adults. However, results should be interpreted cautiously owing to the low number of studies, high risk of bias, and unexplained heterogeneity that may include probiotic strain-specific or prebiotic-specific effects. This review was registered at PROSPERO as CRD42020200670.

Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.

Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals.We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free.These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.

Microbial metabolite indole-3-propionic acid supplementation does not protect mice from the cardiometabolic consequences of a Western diet.

Emerging evidence suggests that intestinal microbes regulate host physiology and cardiometabolic health, although the mechanism(s) by which they do so is unclear. Indoles are a group of compounds produced from bacterial metabolism of the amino acid tryptophan. In light of recent data suggesting broad physiological effects of indoles on host physiology, we examined whether indole-3-propionic acid (IPA) would protect mice from the cardiometabolic consequences of a Western diet. Male C57BL/6J mice were fed either a standard diet (SD) or Western diet (WD) for 5 mo and received normal autoclaved drinking water or water supplemented with IPA (0.1 mg/mL; SD + IPA and WD + IPA). WD feeding led to increased liver triglycerides and makers of inflammation, with no effect of IPA. At 5 mo, arterial stiffness was significantly higher in WD and WD + IPA compared with SD (WD: 485.7 ± 6.7 and WD + IPA: 492.8 ± 8.6 vs. SD: 436.9 ± 7.0 cm/s, P < 0.05) but not SD + IPA (SD + IPA: 468.1 ± 6.6 vs. WD groups, P > 0.05). Supplementation with IPA in the SD + IPA group significantly increased glucose AUC compared with SD mice (SD + IPA: 1,763.3 ± 92.0 vs. SD: 1,397.6 ± 64.0, P < 0.05), and no significant differences were observed among either the WD or WD + IPA groups (WD: 1,623.5 ± 77.3 and WD + IPA: 1,658.4 ± 88.4, P > 0.05). Gut microbiota changes were driven by WD feeding, whereas IPA supplementation drove differences in SD-fed mice. In conclusion, supplementation with IPA did not improve cardiometabolic outcomes in WD-fed mice and may have worsened some parameters in SD-fed mice, suggesting that IPA is not a critical signal mediating WD-induced cardiometabolic dysfunction downstream of the gut microbiota.NEW & NOTEWORTHY The gut microbiota has been shown to mediate host health. Emerging data implicate gut microbial metabolites of tryptophan metabolism as potential important mediators. We examined the effects of indole-3-propionic acid in Western diet-fed mice and found no beneficial cardiometabolic effects. Our data do not support the supposition that indole-3-propionic acid (IPA) mediates beneficial metabolic effects downstream of the gut microbiota and may be potentially deleterious in higher circulating levels.

Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity.

The gut microbiota has emerged as an important regulator of host physiology, with recent data suggesting a role in modulating cardiovascular health. The present study determined if gut microbial signatures could transfer cardiovascular risk phenotypes between lean and obese mice using cecal microbiota transplantation (CMT). Pooled cecal contents collected from obese leptin-deficient (Ob) mice or C57Bl/6j control (Con) mice were transplanted by oral gavage into cohorts of recipient Ob and Con mice maintained on identical low-fat diets for 8 wk (n = 9-11/group). Cardiovascular pathology was assessed as the degree of arterial stiffness (aortic pulse wave velocity) and myocardial infarct size following a 45/120 min ex vivo global cardiac ischemia-reperfusion protocol. Gut microbiota was characterized by 16S rDNA sequencing, along with measures of intestinal barrier function and cecal short-chain fatty acid (SCFA) composition. Following CMT, the gut microbiota of recipient mice was altered to resemble that of the donors. Ob CMT to Con mice increased arterial stiffness, left ventricular (LV) mass, and myocardial infarct size, which were associated with greater gut permeability and reduced cecal SCFA concentrations. Conversely, Con CMT to Ob mice increased cecal SCFA, reduced LV mass, and attenuated myocardial infarct size, with no effects on gut permeability or arterial stiffness. Collectively, these data demonstrate that obesity-related changes in the gut microbiota, independent of dietary manipulation, regulate hallmark measures of cardiovascular pathology in mice and highlight the potential of microbiota-targeted therapeutics for reducing cardiovascular pathology and risk in obesity.NEW & NOTEWORTHY These data are the first to demonstrate that cecal microbiota transplantation (CMT) can alter cardiovascular pathology in lean and obese mice independent from alterations in dietary intake. Myocardial infarct size was reduced in obese mice receiving lean CMT and worsened in lean mice receiving obese CMT. Lean mice receiving obese CMT also displayed increased aortic stiffness. These changes were accompanied by alterations in short-chain fatty acids and gut permeability.

Monounsaturated fatty acids protect against palmitate-induced lipoapoptosis in human umbilical vein endothelial cells.

Diets high in saturated fatty acids are linked to increased cardiovascular disease risk, whereas monounsaturated fatty acids have been associated with improved cardiovascular outcomes. Accordingly, cell culture studies have demonstrated that saturated fatty acids, particularly long chain saturated fatty acids such as palmitate, induce dysfunction and cell death in a variety of cell types, and monounsaturated fatty acids may confer protection against palmitate-mediated damage. The aim of the present study was to examine whether monounsaturated fatty acids could protect against palmitate-mediated cell death in endothelial cells, to determine if AMPK inactivation and activation (via compound C and AICAR, respectively) underlies both palmitate-induced damage and monounsaturated fatty acid-mediated protection, and to explore the role of ER stress in this context. Human umbilical vein endothelial cells were examined for cell viability and apoptosis following treatment for 24 hours with palmitate (0.25 and 0.5mM) alone or in combination with the monounsaturated fatty acids oleate or palmitoleate (0.25 and 0.5mM), AICAR, compound C, 4µ8C, or TUDCA. Compared to control cells, palmitate significantly decreased cell viability and increased apoptosis in a dose-dependent manner. The monounsaturated fatty acids oleate and palmitoleate completely prevented the cytotoxic effects of palmitate. Although palmitate induced markers of ER stress, chemical inhibition of ER stress did not prevent palmitate-induced lipoapoptosis. Conversely, the AMPK activator AICAR (0.1 and 0.5mM) conferred protection from palmitate mediated-alterations in viability, apoptosis and ER stress, whereas the AMPK inhibitor compound C (20 and 40µM) significantly exacerbated palmitate-mediated damage. Lastly, co-incubation with palmitate, monounsaturated fatty acids, and compound C significantly mitigated the protective effects of both oleate and palmitoleate. In conclusion, monounsaturated fatty acids confer protection against the cytotoxic effects of palmitate in vascular endothelial cells; and palmitate-mediated damage, as well as monounsaturated-mediated protection, are due in part to inactivation and activation, respectively, of the metabolic regulator AMPK. These results may have implications for understanding the deleterious effects of high saturated fat diets on cardiovascular dysfunction and disease risk.

SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice.

BACKGROUND: Type 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism. The aim of the current study was to examine if dapagliflozin, a widely prescribed STLT2i, improves generalized vascular dysfunction in type 2 diabetic mice. In light of several studies demonstrating a bi-directional relation between orally ingested medications and the gut microbiota, a secondary aim was to determine the effects of dapagliflozin on the gut microbiota. METHODS: Male diabetic mice (Db, n = 24) and control littermates (Con; n = 23) were randomized to receive either a standard diet or a standard diet containing dapagliflozin (60 mg dapagliflozin/kg diet; 0.006%) for 8 weeks. Arterial stiffness was assessed by aortic pulse wave velocity; endothelial function and vascular smooth muscle dysfunction were assessed by dilatory responses to acetylcholine and sodium nitroprusside, respectively. RESULTS: Compared to untreated diabetic mice, diabetic mice treated with dapagliflozin displayed significantly lower arterial stiffness (Db = 469 cm/s vs. Db + dapa = 435 cm/s, p < 0.05), and improvements in endothelial dysfunction (area under the curve [AUC] Db = 57.2 vs. Db + dapa = 117.0, p < 0.05) and vascular smooth muscle dysfunction (AUC, Db = 201.7 vs. Db + dapa = 285.5, p < 0.05). These vascular improvements were accompanied by reductions in hyperglycemia and circulating markers of inflammation. The microbiota of Db and Con mice were distinctly different, and dapagliflozin treatment was associated with minor alterations in gut microbiota composition, particularly in Db mice, although these effects did not conclusively mediate the improvements in vascular function. CONCLUSIONS: Dapagliflozin treatment improves arterial stiffness, endothelial dysfunction and vascular smooth muscle dysfunction, and subtly alters microbiota composition in type 2 diabetic mice. Collectively, the improvements in generalized vascular function may represent an important mechanism underlying the cardiovascular benefits of SGLT2i treatment.

The gut microbiota as a novel regulator of cardiovascular function and disease.

The gut microbiome has emerged as a critical regulator of human physiology. Deleterious changes to the composition or number of gut bacteria, commonly referred to as gut dysbiosis, has been linked to the development and progression of numerous diet-related diseases, including cardiovascular disease (CVD). Most CVD risk factors, including aging, obesity, certain dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites that may facilitate the development of CVD. The aim of the current review is to summarize the available data regarding the role of the gut microbiome in regulating CVD function and disease processes. Particular emphasis is placed on nutrition-related alterations in the microbiome, as well as the underlying cellular mechanisms by which the microbiome may alter CVD risk.

Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction.

Vascular dysfunction represents a critical preclinical step in the development of cardiovascular disease. We examined the role of the gut microbiota in the development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed either a standard diet (SD) ( n = 12) or Western diet (WD) ( n = 24) for 5 mo, after which time WD mice were randomized to receive either unsupplemented drinking water or water containing a broad-spectrum antibiotic cocktail (WD + Abx) ( n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased arterial stiffness (SD 412.0 ± 6.0 vs. WD 458.3 ± 9.0 cm/s, P < 0.05) and endothelial dysfunction (28% decrease in max dilation, P < 0.05), and reduced l-NAME-inhibited dilation. Vascular dysfunction was accompanied by significant increases in circulating LPS-binding protein (LBP) (SD 5.26 ± 0.23 vs. WD 11 ± 0.86 µg/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 ± 0.25 vs. WD 7.09 ± 1.07 pg/ml, P < 0.05); aortic expression of phosphorylated nuclear factor-κB (p-NF-κB) ( P < 0.05); and perivascular adipose expression of NADPH oxidase subunit p67phox ( P < 0.05). Impairments in vascular function correlated with reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated the gut microbiota and reversed WD-induced arterial stiffness and endothelial dysfunction. These improvements were accompanied by significant reductions in LBP, IL-6, p-NF-κB, and advanced glycation end products (AGEs), and were independent from changes in body weight and glucose tolerance. These results indicate that gut dysbiosis contributes to the development of WD-induced vascular dysfunction, and identify the gut microbiota as a novel therapeutic target for obesity-related vascular abnormalities.

Tauroursodeoxycholic Acid Reduces Arterial Stiffness and Improves Endothelial Dysfunction in Type 2 Diabetic Mice.

BACKGROUND/AIMS: Endoplasmic reticulum (ER) stress has emerged as a potential mechanism contributing to diabetes and its comorbidities. However, the importance of ER stress in diabetic vascular dysfunction is unclear. The purpose of this study was to examine the effects of the ER stress inhibitor, tauroursodeoxycholic acid (TUDCA), on arterial stiffness and endothelial dysfunction in type 2 diabetic mice. METHODS: Carotid and mesenteric artery endothelial function were assessed via ex vivo pressure myography, and arterial stiffness was measured by aortic pulse wave velocity. The effects of TUDCA were examined both acutely (ex vivo) and chronically (250 mg/kg/day; i.p., 4 weeks). RESULTS: Compared to control C57BL/6J mice, db/db (DB) mice did not display carotid artery endothelial dysfunction; however, mesenteric artery endothelial function was markedly impaired. Acute incubation and chronic administration of TUDCA improved endothelium-dependent dilation in DB mesenteric arteries, without affecting endothelium-independent dilation. Chronic TUDCA administration also reduced arterial stiffness and was associated with reductions in ER stress markers in aortic and perivascular adipose tissue. CONCLUSIONS: These results suggest that ER stress may represent a novel cause of, and therapeutic target for, diabetic vascular dysfunction.

Fuzhuan tea reverses arterial stiffening after modest weight gain in mice.

OBJECTIVES: The aim of this study was to examine the effects of a Western diet (WD) and supplementation with Fuzhuan tea on large artery stiffness, as determined by aortic pulse wave velocity (aPWV). METHODS: Mice were subjected to a standard diet (SD; n = 12) or WD (n = 10) for 7 mo, and were then separated to receive nonsupplemented drinking water (SD-W and WD-W) or water supplemented with Fuzhuan tea (SD-T and WD-T) (200 mg/kg daily); mice were then maintained on their respective diets for an additional 2 mo. RESULTS: After the initial 7-mo feeding period, WD elicited a modest and significantly greater increase in body weight than did SD (39.6 ± 0.71 versus 34.5 ± 1.16 g; P < 0.01). PWV was significantly elevated in WD but not in SD (459.3 ± 4.8 versus 422.4 ± 6.4 cm/s; P < 0.001). Following an additional 2 mo, PWV continued to increase in WD-W, but returned to control levels in WD-T (WD-W: 519.8 ± 12.8; WD-T: 426.5 ± 18.6; SD-W: 429.7 ± 8.6; SD-T: 429.1 ± 6.1 cm/s; P < 0.001, WD-W versus all groups). The increase in PWV in WD-W was accompanied by an increase in aortic collagen (WD-W: 38.8 ± 4.6 versus SD-W: 17.5 ± 5.1 percent cross-sectional area; P < 0.05). CONCLUSION: The results of the present study suggest that the increase in arterial stiffness after modest, diet-induced weight gain can be reversed by supplementation with Fuzhuan tea.