Postprandial serum endotoxin in healthy humans is modulated by dietary fat in a randomized, controlled, cross-over study

Background: High-fat diets may contribute to metabolic disease via postprandial changes in serum endotoxin and inflammation. It is unclear how dietary fat composition may alter these parameters. We hypothesized that a meal rich in n-3 (ω3) fatty acids would reduce endotoxemia and associated inflammation but a saturated or n-6 (ω6) fatty acid-rich meal would increase postprandial serum endotoxin concentrations and systemic inflammation in healthy adults. Methods: Healthy adults (n = 20; mean age 25 ± 3.2 S.D. years) were enrolled in this single-blind, randomized, cross-over study. Participants were randomized to treatment and reported to the laboratory, after an overnight fast, on four occasions separated by at least one week. Participants were blinded to treatment meal and consumed one of four isoenergetic meals that provided: 1) 20 % fat (control; olive oil) or 35 % fat provided from 2) n-3 (ω3) (DHA = 500 mg; fish oil); 3) n-6 (ω6) (7.4 g; grapeseed oil) or 4) saturated fat (16 g; coconut oil). Baseline and postprandial blood samples were collected. Primary outcome was defined as the effect of treatment meal on postprandial endotoxemia. Serum was analyzed for metabolites, inflammatory markers, and endotoxin. Data from all 20 participants were analyzed using repeated-measures ANCOVA. Results: Participant serum endotoxin concentration was increased during the postprandial period after the consumption of the saturated fat meal but decreased after the n-3 meal (p  0.05). There was no treatment meal effect on participant postprandial serum biomarkers of inflammation. Postprandial serum triacylglycerols were significantly elevated following the n-6 meal compared to the n-3 meal. Non-esterified fatty acids were significantly increased after consumption of the saturated fat meal compared to other treatment meals. Conclusions: Meal fatty acid composition modulates postprandial serum endotoxin concentration in healthy adults. However, postprandial endotoxin was not associated with systemic inflammation in vivo. Trial registration: This study was retrospectively registered at clinicaltrials.gov as NCT02521779 on July 28, 2015

Gut microbiota and brain function: an evolving field in neuroscience

There is a growing appreciation of the importance of gut microbiota to health and disease. This has been driven by advances in sequencing technology and recent findings demonstrating the important role of microbiota in common health disorders such as obesity. Moreover, the potential role of gut microbiota in influencing brain function, behavior, and mental health has attracted the attention of neuroscientists and psychiatrists. At the 29th International College of Neuropsychopharmacology (CINP) World Congress held in Vancouver, Canada, in June 2014, a group of experts presented the symposium, “Gut microbiota and brain function: Relevance to psychiatric disorders” to review the latest findings in how gut microbiota may play a role in brain function, behavior, and disease. The symposium covered a broad range of topics, including gut microbiota and neuroendocrine function, the influence of gut microbiota on behavior, probiotics as regulators of brain and behavior, and imaging the gut-brain axis in humans. This report provides an overview of these presentations

Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs

peer-reviewedBackground: Carotid body (peripheral oxygen sensor) sensitisation is pivotal in the development of chronic intermittent hypoxia (CIH)-induced hypertension. We sought to determine if exposure to CIH, modelling human sleep apnoea, adversely affects cardiorespiratory control in guinea-pigs, a species with hypoxia-insensitive carotid bodies. We reasoned that CIH-induced disruption of gut microbiota would evoke cardiorespiratory morbidity. Methods: Adult male guinea-pigs were exposed to CIH (6.5% O2 at nadir, 6 cycles.hour−1) for 8 h.day−1 for 12 consecutive days. Findings: CIH-exposed animals established reduced faecal microbiota species richness, with increased relative abundance of Bacteroidetes and reduced relative abundance of Firmicutes bacteria. Urinary corticosterone and noradrenaline levels were unchanged in CIH-exposed animals, but brainstem noradrenaline concentrations were lower compared with sham. Baseline ventilation was equivalent in CIH-exposed and sham animals; however, respiratory timing variability, sigh frequency and ventilation during hypoxic breathing were all lower in CIH-exposed animals. Baseline arterial blood pressure was unaffected by exposure to CIH, but β-adrenoceptor-dependent tachycardia and blunted bradycardia during phenylephrine-induced pressor responses was evident compared with sham controls. Interpretation: Increased carotid body chemo-afferent signalling appears obligatory for the development of CIH-induced hypertension and elevated chemoreflex control of breathing commonly reported in mammals, with hypoxia-sensitive carotid bodies. However, we reveal that exposure to modest CIH alters gut microbiota richness and composition, brainstem neurochemistry, and autonomic control of heart rate, independent of carotid body sensitisation, suggesting modulation of breathing and autonomic homeostasis via the microbiota-gut-brainstem axis. The findings have relevance to human sleep-disordered breathing

Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri

Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2[superscript −/−] mice, indicating the effects of the stressor are CCL2-dependent. In addition, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through downregulation of the chemokine CCL2.National Cancer Institute (U.S.) (Grants AT006552-01A1, P30-CA016058, and T32-DE014320

A translational investigation into the role of dietary fatty acids in modulating endotoxemia and associated inflammation

The presence of bacterial endotoxin in the bloodstream, known as endotoxemia, may cause inflammation and play a role in the development of chronic disease. Dietary fatty acid composition has been demonstrated, albeit inconsistently in different animal species, to modulate endotoxemia potentially via altered lipopolysaccharide (LPS) absorption from the intestinal lumen. We first sought to uncover whether postprandial endotoxemia in healthy people is influenced by the consumption of meals rich in saturated or long-chain n(ω)-3 fatty acids, respectively. Considering the physiological similarity of the human and porcine gastrointestinal tracts, the effect on endotoxemia from long-term consumption of high fat diets distinct in fatty acid composition was examined in pigs. Mechanistic investigations were performed in porcine tissue in vitro and ex vivo to understand how dietary fatty acids might differently regulate LPS transport and LPS-induced inflammation at the intestinal epithelium. Previous studies using human participants have indicated that the consumption of a high-fat meal is associated with increased postprandial endotoxemia and circulating markers of inflammation. However, it was unclear whether this effect was dependent on high or low fat content or the fatty acid composition of the meal. To address this question, healthy adult men and women were recruited for a randomized cross-over study in which participants consumed a low-fat meal, or one of three high-fat meals containing saturated, n-3, or n-6 fatty acids. Serum endotoxin concentration was lower (p\u3c0.05) following the consumption of an n-3 fatty-acid rich meal compared to serum endotoxin concentration after the consumption of a saturated fatty acid-rich meal. Postprandial endotoxemia was not different depending on whether the participant had consumed a low-fat content or high fat content meal. Despite alterations in blood endotoxin, none of the meals were found to impact biomarkers of systemic inflammation. These results suggest the modulatory effect of a high fat meal on blood endotoxin concentration is dependent on the fatty acid composition, but not total fat content of a meal. Next, we used a porcine jejunum epithelial cell line, IPEC-J2, to investigate in vitro a potential mechanism for common dietary fatty acid mediation of LPS transit across the small intestine epithelium where fatty acids are absorbed in vivo. However, our investigation did not find LPS to transit across the IPEC-J2 polarized monolayer regardless of the presence of saturated, n-3, or n-6 fatty acids. Since chemically-purified LPS does not exist in vivo but is instead found within bacterial membrane fragments or in live bacteria, we also sought to determine whether the inflammatory effect of purified versus in vivo-relevant forms of LPS differently elicit inflammation and if these sources of inflammation are commonly modulated, and via what pathway, by dietary fatty acids. We found purified LPS to stimulate comparatively less (p\u3c0.05) inflammation than native forms of LPS. Moreover, long chain polyunsaturated fatty acids inhibited (p\u3c0.05) LPS-induced production of inflammatory cytokines via a TLR4 pathway, whereas medium chain saturated fatty acids did not alter (p\u3e0.05) normal inflammatory response. These results indicate that purified and native forms of LPS behave differently in in vitro cell culture suggesting mechanistic investigations for in vivo uptake of LPS from the gut lumen should use in vivoìì-relevant forms of LPS. Little is known about how long-term consumption of high fat diets that differ in dietary fatty acid composition alter endotoxemia. We used a pig model to investigate how daily consumption of a low fat, high fat, or high fat diet with n-3 fatty acids over 9 weeks influences endotoxemia. An effect of the fat composition of the diet on endotoxemia was not found (p\u3e0.05). Pig jejunum segments were harvested from these animals and mounted in Ussing chambers to assess the flux of LPS and live E. coli. It was found that while LPS did not cross the intestinal epithelium under any condition, the transit of live bacteria was influenced by diet. Significantly more (p\u3c0.05) E. coli transited across jejunum from a high fat diet animal than from either a low fat or high fat with n-3 fatty acid animal. This effect was due to the effect of a high fat diet in increasing passage of bacteria is mitigated by consumption of n-3 fatty acids via a TLR4-dependent pathway. These results suggest the acute modulatory effect of a novel high fat meal on postprandial endotoxemia may not persist with repeated consumption of the same meal-type. Moreover, endotoxemia from the gut may be related to passage of Gram negative bacteria but not uptake of LPS

A pilot study on the effects of probiotic supplementation on neuropsychological performance and microRNA-29a-c levels in antiretroviral-treated HIV-1-infected patients

The gut microbiota is involved in the regulation of cognition, mood, anxiety, and pain, and can impact cognitive functions by producing neuroactive substances or releasing bacterial by-products and metabolites. No information is available on the effects of a probiotic supplementation on brain function of HIV+ subjects. In light of the above considerations, we performed a pilot study in cART-treated HIV-1-positive patients with long-term virologic suppression. The aims were to analyze the effect of high-concentration multistrain probiotic supplementation (Vivomixx®; Visbiome®) on several neurocognitive abilities and to evaluate the safety of this supplementation

Understanding the Barriers, Bridges and Bases to Inclusion Instruction for Secondary Students with Mild to Moderate Disabilities

Inclusion is the practice of educating students with disabilities and students without disabilities in the same learning environment. For secondary students with mild/moderate disabilities, inclusion is rooted in the philosophical mindset of social justice, equity, and legislation. Inclusion is a complex and sometimes controversial topic few educational systems want to tackle. The purpose of this multi-method research was to gather and analyze secondary site administrators\u27 and teachers’ opinions on the barriers, bridges, and bases needed for the furtherance of inclusion practices and the elimination of the segregated classrooms for students with mild-moderate disabilities. A plethora of research on this topic exists, yet there remains a gap in the literature of understanding what secondary staff needs for inclusion to move from theory to practice. One hundred and seven teachers and administrators participated in this research with mixed results. This study found that positive beliefs about inclusion are necessary but not sufficient to override the need for collaboration time, preservice training, qualified personnel, and district level administrative support

Peptides as quorum sensing molecules : measurement techniques and obtained levels in vitro and in vivo

The expression of certain bacterial genes is regulated in a cell-density dependent way, a phenomenon called quorum sensing. Both Gram-negative and Gram-positive bacteria use this type of communication, though the signal molecules (auto-inducers) used by them differ between both groups: Gram-negative bacteria use predominantly N-acyl homoserine lacton (AHL) molecules (autoinducer-1, AI-1) while Gram-positive bacteria use mainly peptides (autoinducer peptides, AIP or quorum sensing peptides). These quorum sensing molecules are not only involved in the inter-microbial communication, but can also possibly cross-talk directly or indirectly with their host. This review summarizes the currently applied analytical approaches for quorum sensing identification and quantification with additionally summarizing the experimentally found in vivo concentrations of these molecules in humans