Dietary fiber intake and fecal short-chain fatty acid concentrations are associated with lower plasma lipopolysaccharide-binding protein and inflammation.

Consuming adequate dietary fiber is a promising strategy for reducing systemic inflammation. The objective was to evaluate relationships between dietary fiber intake, markers of metabolic endotoxemia, and systemic inflammation in adults. This was a cross-sectional study of 129 healthy participants (age 33.6 ± 6.1 yr, BMI 30.5 ± 6.9 kg/m2). Dietary fiber intake was assessed by food frequency questionnaire. Adiposity was measured using dual-energy X-ray absorptiometry (DXA). Fecal short-chain fatty acids (SCFA) were quantified using gas chromatography-mass spectrometry. Fecal microbiota sequence data (V4 region, 16S rRNA gene) were analyzed using DADA2 and QIIME2. Inflammatory cytokines were assessed with enzyme-linked immunosorbent assays; flow cytometry was conducted for monocyte surface marker quantification. Bivariate correlations and generalized step-wise linear modeling were used for statistical analyses. Plasma C-reactive protein (CRP) and interleukin (IL)-6 concentrations were positively related to whole body (CRP r = 0.45, P = <0.0001; IL-6 r = 0.34, P = 0.0002) and visceral adiposity (CRP r = 0.33, P = 0.0003; IL-6 r = 0.38, P = 0.0002). Plasma lipopolysaccharide-binding protein (LBP) concentrations were inversely related to dietary fiber intake (r = -0.22, P = 0.03) and fecal SCFA (acetate r = -0.25, P = 0.01; propionate r = -0.28, P = 0.003; butyrate r = -0.23, P = 0.02). Whole body adiposity, dietary fiber, and fecal SCFA were the most predictive of plasma LBS-BP concentrations. Novel findings included associations between dietary fiber intake, the gastrointestinal microbiota, and systemic inflammation.NEW & NOTEWORTHY Dietary fiber intake may reduce the inflammation associated with obesity and metabolic disease. Our cross-sectional analysis revealed that dietary fiber intake and fecal short-chain fatty acids are inversely associated with lipopolysaccharide-binding protein, a marker of systemic inflammation. In addition, plasma interleukin-6 and C-reactive protein were positively related to markers of adiposity.

Prebiotic Consumption Alters Microbiota but Not Biological Markers of Stress and Inflammation or Mental Health Symptoms in Healthy Adults: A Randomized, Controlled, Crossover Trial.

BACKGROUND: Chronic stress contributes to systemic inflammation and diminished mental health. Although animal work suggests strong links with the microbiota-gut-brain axis, clinical trials investigating the effectiveness of prebiotics in improving mental health and reducing inflammation are lacking. OBJECTIVES: We aimed to determine fructooligosaccharide (FOS) and galactooligosaccharide (GOS) effects on biological markers of stress and inflammation and mental health symptoms in adults. Secondary outcomes included fecal microbiota and metabolites, digestive function, emotion, and sleep. METHODS: Twenty-four healthy adults (25-45 y; 14 females, 10 males; BMI, 29.3 ± 1.8 kg/m2) from central Illinois participated in a 2-period, randomized, controlled, single-blinded crossover trial. Interventions included the prebiotic (PRE) treatment (237 mL/d Lactaid low-fat 1% milk, 5 g/d FOS, 5 g/d GOS) and control (CON) (237 mL/d Lactaid), which were consumed in counterbalanced order for 4 wk each, separated by ≥4-wk washout. Inflammatory markers were measured in blood plasma (>10-h fast) and cortisol in urine. The Depression Anxiety Stress Scales-42 assessed mental health symptoms. Fecal samples were collected for 16S rRNA gene (V4 region) sequencing and analysis. Emotion was measured by rating images from a computer task. Sleep was assessed using 7-d records and accelerometers. Change scores were analyzed using linear mixed models with treatment and baseline covariate as fixed effects and participant ID as the random effect. RESULTS: There were no differences in change scores between PRE and CON treatments on biological markers of stress and inflammation or mental health. PRE increased change in percent sequences (q = 0.01) of Actinobacteriota (CON: 0.46 ± 0.70%; PRE: 5.40 ± 1.67%) and Bifidobacterium (CON: -1.72 ± 0.43%; PRE: 4.92 ± 1.53%). There were also no differences in change scores between treatments for microbial metabolites, digestive function, emotion, or sleep quality. CONCLUSIONS: FOS+GOS did not affect biological markers of stress and inflammation or mental health symptoms in healthy adults; however, it increased Bifidobacterium. CLINICAL TRIAL REGISTRY: NCT04551937, www. CLINICALTRIALS: gov.

Consumption of a fermented dairy beverage improves hippocampal-dependent relational memory in a randomized, controlled cross-over trial.

Objectives: We aimed to determine whether consumption of a fermented dairy beverage containing probiotic microorganisms influences negative mood states, stress, and hippocampal memory performance in healthy adults. Methods: Adults (25-45 yrs, N = 26) free of gastrointestinal and mental illness were enrolled in a single-blind, randomized, controlled, crossover trial. Participants completed testing prior to and after 4-week consumption, with a 2-4 week washout between treatments of: (1) 8 oz of a dairy-based fermented beverage containing 25-30 billion colony forming units of live and active kefir cultures or (2) 8 oz isocaloric, non-fermented, 1% low-fat lactose-free dairy-based control beverage. Hippocampal-dependent relational memory was assessed using a spatial reconstruction task. Negative mood states of depression and anxiety were assessed using the Depression Anxiety Stress Scales-42 (DASS-42). Pooled 24-hour urine samples were analyzed using an enzyme-linked immunosorbent assay to determine urinary free-cortisol (UFC) concentrations. Fecal microbiota composition was assessed using 16S rRNA gene sequencing. Results: Lactobacillus was increased by 235% following fermented dairy consumption compared to the control (p < .01). Furthermore, the fermented dairy beverage improved performance on two metrics of relational memory, misplacement (p = .04) and object-location binding (p = .03). UFC and DASS-42 scores (all p's > .08) were not significantly changed by either arm of the intervention. No correlations were observed between the change in Lactobacillus and memory performance. Conclusions: Fermented dairy consumption increased the presence of certain microorganisms in the gut and improved relational memory in healthy adults. However, the benefits observed for relational memory were not related to changes in Lactobacillus.Trial registration: ClinicalTrials.gov identifier: NCT02849275.

Systemic inflammation mediates the negative relationship between visceral adiposity and cognitive control.

Elevated visceral adipose tissue (VAT) has been associated with cardiometabolic risk factors including chronic systemic low-grade inflammation. Whereas the cognitive implications of inflammation have been extensively studied in preclinical models, the influence of inflammatory cytokines on cognitive function in humans is unclear. This study aimed to investigate the relations among VAT, inflammatory cytokines, and cognitive control. We hypothesized that inflammatory markers would mediate the negative influence of VAT on selective attention. Participants between 25 and 46 years (N = 115, 43 females) underwent a DXA scan to estimate VAT. A modified Eriksen Flanker task was used to assess attentional inhibitory control while event-related potentials were recorded. ELISA was used to quantify plasma C-reactive protein (CRP) and Interleukin-6 (IL-6) concentrations. Mediation modeling while controlling for diet quality and education level revealed that CRP concentrations significantly mediated the relationship between VAT and incongruent trial accuracy (indirect effect 95% CI {-0.24, -0.01}). Further, IL-6 concentrations had a significant mediation effect on the relationship between VAT and incongruent P3 peak latency (indirect effect 95% CI {0.05, 1.39}). These results suggest that mechanisms by which visceral adiposity exerts a negative influence on cognitive function includes systemic inflammation.

Avocado Consumption Alters Gastrointestinal Bacteria Abundance and Microbial Metabolite Concentrations among Adults with Overweight or Obesity: A Randomized Controlled Trial.

BACKGROUND: Avocados are rich in dietary fiber and monounsaturated fatty acids (MUFAs), nutrients that have been independently connected to metabolic health benefits and the gastrointestinal microbiota. OBJECTIVES: We aimed to evaluate the impact of avocado consumption on the gastrointestinal microbiota and microbial metabolites, secondary outcomes of the Persea americana for Total Health (PATH) study, and conduct exploratory analyses to assess relations between the fecal microbiota, fecal metabolites, and health markers. METHODS: Adults [n = 163, 25-45 y, BMI (kg/m2) ≥ 25.0] were enrolled in the PATH study, a 12-wk investigator-blinded trial where participants were batch randomized to match the 2 groups by age, sex, visceral adiposity, and fasting glucose concentrations. Participants consumed isocaloric meals with or without avocado (175 g, men; 140 g, women) once daily for 12 wk. The fecal microbiota was assessed with 16S ribosomal RNA gene (V4 region) sequencing and analysis using DADA2 and QIIME2. Fecal fatty acid and bile acid concentrations were quantified using GC and LC-MS. Per-protocol (≥80% meal consumption) and intent-to-treat analyses were conducted using univariate ANOVA and Mann-Whitney U tests. Bivariate correlations were conducted between fecal microbiota, fecal metabolites, and health measures. RESULTS: The avocado treatment increased ɑ diversity and enriched Faecalibacterium, Lachnospira, and Alistipes between 26% and 65% compared with the control group. The avocado group had 18% greater fecal acetate, 70% greater stearic acid, and 98% greater palmitic acid concentrations than the control group, while the concentrations of the bile acids cholic and chenodeoxycholic acid were 91% and 57% lower, respectively. CONCLUSIONS: Daily avocado consumption resulted in lower fecal bile acid concentrations, greater fecal fatty acid and SCFAs, and greater relative abundances of bacteria capable of fiber fermentation, providing evidence that this nutrient-dense food affects digestive physiology, as well as the composition and metabolic functions of the intestinal microbiota. This trial was registered at www.clinicaltrials.gov as NCT02740439.

Microbiome-Mediated Effects of the Mediterranean Diet on Inflammation.

The Mediterranean diet pattern is increasingly associated with improved metabolic health. Two mechanisms by which consuming a Mediterranean diet pattern may contribute to improved metabolic health are modulation of the gastrointestinal (GI) microbiota and reduction of metabolic endotoxemia. Metabolic endotoxemia, defined as a 2- to 3-fold increase in circulating levels of bacterial endotoxin, has been proposed as a cause of inflammation during metabolic dysfunction. As the largest source of endotoxins in the human body, the GI microbiota represents a crucial area for research on strategies for reducing endotoxemia. Diets high in saturated fat and low in fiber contribute to metabolic endotoxemia through several mechanisms, including changes in the GI microbiome and bacterial fermentation end products, intestinal physiology and barrier function, and enterohepatic circulation of bile acids. Thus, the Mediterranean diet pattern, rich in unsaturated fats and fiber, may be one dietary strategy to reduce metabolic endotoxemia. Preclinical studies have demonstrated the differential effects of dietary saturated and unsaturated fats on the microbiota and metabolic health, but human studies are lacking. The role of dietary fiber and the GI microbiome in metabolic endotoxemia is underinvestigated. Clinical research on the effects of different types of dietary fat and fiber on the GI microbiota and GI and systemic inflammation is necessary to determine efficacious dietary strategies for reducing metabolic endotoxemia, inflammation, and subsequent metabolic disease.