Modulation Of Microbiota Composition Research Articles

Gut Microbiota Composition and Metabolites as the new Determinants of Cardiovascular Pathology Development

Chronic noncommunicable diseases represent one of the key medical problems of the XXI century. In this group cardiovascular diseases (CVD) are known to be the leading cause of death which pathogenesis still has the potential to be more profoundly revealed in order to discover its yet unknown but essential factors. The last decades are marked by the active investigation into the gut bacterial role in the initiation and progression of CVD. The result of this investigation has been the appreciation of microbiome as the potentially new cardiovascular risk factor. The development of sequencing techniques, together with bioinformatics analysis allowed the scientists to intensively broaden the understanding of the gut microbiota composition and functions of its metabolites in maintaining the health and the development of atherosclerosis, arterial hypertension and heart failure. The interaction between macro- and microorganisms is mediated through the variety of pathways, among which the key players are thought to be trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA) and secondary bile acids. TMAO is known due to its role in atherosclerosis development and the increase in major cardiovascular events. In the majority of research SCFA and secondary bile acids have demonstrated protective role in CVD. The great attention is being paid to the role of lipopolysaccharide of gram negative bacteria in the development of systemic low-grade inflammation due to the metabolic endotoxemia which contributes to the progression of CVD. The described interactions draw attention to the opportunity to influence on the certain mechanisms of CVD pathogenesis through the modulation of microbiota composition and function. The review is aimed at highlighting the current data about the mechanisms by which the gut microbiota and its metabolites may increase cardiovascular risk and events rate as well as discussing the existing results and future perspective of bacterial systemic effects modulation.

Fibroblast Growth Factor 19 modulates intestinal microbiota and inflammation in presence of Farnesoid X Receptor.

BackgroundDisruption of bile acid (BA) homeostasis plays a key role in intestinal inflammation. The gut-liver axis is the main site for the regulation of BA synthesis and BA pool size via the combined action of the nuclear Farnesoid X Receptor (FXR) and the enterokine Fibroblast Growth Factor 19 (FGF19). Increasing evidence have linked derangement of BA metabolism with dysbiosis and mucosal inflammation. Thus, here we aimed to investigate the potential action of an FGF19 analogue on intestinal microbiota and inflammation.MethodsA novel engineered non-tumorigenic variant of the FGF19 protein, M52-WO 2016/0168219 was generated. WT and FXRnull mice were injected with AAV-FGF19-M52 or the control AAV-GFP and subjected to Sodium Dextran Sulphate-induced colitis.FindingsFGF19-M52 reduced BA synthesis and pool size, modulated its composition and protected mice from intestinal inflammation. These events were coupled with preservation of the intestinal epithelial barrier integrity, inhibition of inflammatory immune response and modulation of microbiota composition. Interestingly, FGF19-M52-driven systemic and local anti-inflammatory activity was completely abolished in Farnesoid X Receptor (FXR)null mice, thus underscoring the need of FXR to guarantee enterocytes’ fitness and complement FGF19 anti-inflammatory activity. To provide a translational perspective, we also show that circulating FGF19 levels are reduced in patients with Crohn's disease.InterpretationReactivation of the FXR-FGF19 axis in a murine model of intestinal inflammation could bona fide provide positive changes in BA metabolism with consequent reduction of intestinal inflammation and modulation of microbiota. These results point to the therapeutic potential of FGF19 in the treatment of intestinal inflammation with concomitant derangement of BA homeostasis.FundingA. Moschetta is funded by MIUR-PRIN 2017 <- 2017J3E2W2; Italian Association for Cancer Research (AIRC, IG 23239); Interreg V-A Greece-Italy 2014-2020-SILVER WELLBEING, MIS5003627; HDHL-INTIMIC EuJPI-FATMAL; MIUR PON “R&I” 2014-2020-ARS01_01220. No money has been paid by NGM Biopharmaceuticals or any other agency to write this article.

Calcium Oxalate Nephrolithiasis and Gut Microbiota: Not just a Gut-Kidney Axis. A Nutritional Perspective.

Recent studies have shown that patients with kidney stone disease, and particularly calcium oxalate nephrolithiasis, exhibit dysbiosis in their fecal and urinary microbiota compared with controls. The alterations of microbiota go far beyond the simple presence and representation of Oxalobacter formigenes, a well-known symbiont exhibiting a marked capacity of degrading dietary oxalate and stimulating oxalate secretion by the gut mucosa. Thus, alterations of the intestinal microbiota may be involved in the pathophysiology of calcium kidney stones. However, the role of nutrition in this gut-kidney axis is still unknown, even if nutritional imbalances, such as poor hydration, high salt, and animal protein intake and reduced fruit and vegetable intake, are well-known risk factors for kidney stones. In this narrative review, we provide an overview of the gut-kidney axis in nephrolithiasis from a nutritional perspective, summarizing the evidence supporting the role of nutrition in the modulation of microbiota composition, and their relevance for the modulation of lithogenic risk.

Sturgeon hydrolysates alleviate DSS-induced colon colitis in mice by modulating NF-κB, MAPK, and microbiota composition.

Sturgeon muscle byproduct collected after caviar production is usually not fully utilized, and sometimes may be discarded, thus causing a lot of waste. Yet dietary protein hydrolysates, which may be derived from sturgeon muscle, have been reported to have versatile beneficial biological activities. Studying the biological activities of sturgeon muscle-derived hydrolysates holds much promise for adding value to sturgeon. The current study aimed to study the therapeutic anti-inflammatory effects of sturgeon muscle-derived hydrolysates and the underlying mechanisms. The administration of sturgeon hydrolysates (SH) significantly decreased the severity of DSS-induced damage, evidenced by increased body weight, colon length, and decreased disease activity index (DAI) and histological scores. SH also inhibited myeloperoxidase (MPO) activity and reduced the serum levels of IL-6, IL-1β, and TNF-α. Western blotting results revealed that SH suppressed DSS-induced activation of the NF-κB and MAPK pathways in the colon. Furthermore, SH partially restored the alteration of the gut microbiota in colitic mice. SH increased the Bacteroidetes/Firmicutes ratio and the relative abundance of Ruminococcaceae, Porphyromonadaceae, and Bacteroidetes S24-7, while decreased the abundance of potentially harmful bacteria Erysipelotrichaceae and Enterococcaceae. These results suggest that SH inhibited DSS-induced colitis by regulating the NF-κB and MAPK pathways and modulating microbiota composition.

Impact of Buckwheat Fermented Milk Combined with High-Fat Diet on Rats' Gut Microbiota and Short-Chain Fatty Acids.

The aim of this study was to evaluate the effect of buckwheat fermented milk on intestinal flora and short-chain fatty acids (SCFAs) of rats fed a high-fat diet (HFD). Buckwheat fermented milk was made with Lactobacillus plantarum ST-Ⅲ, Lactobacillus bulgaricus, and Streptococcus thermophilus. Thirty-six males C57BL/6 rats (aged 3 weeks and with 9 to 12g weight) were subjected to a 2-week adaptive period on a normal diet. After a week of acclimatization, the rats were randomly divided into three groups with 12 rats in each group. The high-fat diet with fermented milk (HFDFM) group received HFD supplemented with fermented milk, and the high-fat diet supplemented with buckwheat fermented milk (HFDBFM) group received HFD plus buckwheat fermented milk. Besides, the gavage dose was 0.4mL/day. After the feedings, colon levels of cytokines and antioxidant indices of the liver, colon, and duodenum tissues were measured. The composition of intestinal flora of rats and the content of SCFAs were determined by gas chromatography-mass spectrometry and Illumina high-throughput sequencing technology. Supplementation with buckwheat fermented milk significantly inhibited the increases in lipopolysaccharide levels in colon and antioxidant indexes in the HFD-fed rats. In addition, buckwheat fermented milk could significantly enhance Firmicutes and decrease Bacteroidetes compared to HFDFM. In addition, SCFA concentrations in HFDBFM were higher than other groups. In conclusion, buckwheat fermented milk can alleviate the damage of HFD to intestinal flora of rats. It modulates microbiota composition and SCFA concentrations to balance the intestinal environment, which will benefit to rats' intestinal health. PRACTICAL APPLICATION: This study explored the effect of buckwheat fermented milk on the regulation of intestinal microflora and SCFAs in rats fed a high-fat diet. It provides new ideas for the development of buckwheat fermented food.

Dietary administration of resistant starch improved caecal barrier function by enhancing intestinal morphology and modulating microbiota composition in meat duck.

Resistant starch (RS) was recently approved to exert a powerful influence on gut health, but the effect of RS on the caecal barrier function in meat ducks has not been well defined. Thus, the effect of raw potato starch (RPS), a widely adopted RS material, on microbial composition and barrier function of caecum for meat ducks was determined. A total of 360 Cherry Valley male ducks of 1-d-old were randomly divided and fed diets with 0 (control), 12, or 24 % RPS for 35d. Diets supplemented with RPS significantly elevated villus height and villus height:crypt depth ratio in the caecum. The 16S rRNA sequence analysis indicated that the diet with 12 % RPS had a higher relative abundance of Firmicutes and the butyrate-producing bacteria Faecalibacterium, Subdoligranulum, and Erysipelatoclostridium were enriched in all diets. Lactobacillus and Bifidobacterium were significantly increased in the 24 % RPS diet v. the control diet. When compared with the control diet, the diet with 12 % RPS was also found to notably increase acetate, propionate and butyrate contents and up-regulated barrier-related genes including claudin-1, zonula occludens-1, mucin-2 and proglucagon in the caecum. Furthermore, the addition of 12 % RPS significantly reduced plasma TNF-α, IL-1β and endotoxin concentrations. These data revealed that diets supplemented with 12 % RPS partially improved caecal barrier function in meat ducks by enhancing intestinal morphology and barrier markers expression, modulating the microbiota composition and attenuating inflammatory markers.

Gut-liver axis signaling in portal hypertension

Portal hypertension (PHT) in advanced chronic liver disease (ACLD) results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition (structural component) and intrahepatic vasoconstriction (functional component). PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding. Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns (PAMPs) that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways. Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability: The intestinal barrier function is affected by impaired microcirculation, neoangiogenesis, and abnormal vascular and mucosal permeability. The close bidirectional relationship between the gut and the liver has been termed “gut-liver axis”. Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function, intestinal barrier integrity, as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects. The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments, however, further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed. In this review, we summarize the clinical impact of PHT on the course of liver disease, discuss the underlying pathophysiological link of PHT to gut-liver axis signaling, and provide insight into molecular mechanisms that may represent novel therapeutic targets.

Inflamm-aging microRNAs may integrate signals from food and gut microbiota by modulating common signalling pathways

Human gut microbiota, which comprises an extremely diverse and complex community of microorganisms inhabiting the intestinal tract, may be associated with inflammation and age-related chronic health conditions. However, the mechanism underlying this association is only recently beginning to emerge. Transfer and modulation of gene expression by diet-derived microRNAs (miRs) in mammals might be involved in this communication. Through a bioinformatics approach, using on line tools and repositories, we searched for evidences that food-containing miRs, actually involved in the modulation of the inflammatory process, (inflamma-miRs), may contribute to mediate the anti-inflammatory effects exerted by some foods through the modulation of aging-related pathways and gut microbiota composition in a bidirectional communication. Supported by a “Pubmed” search and our previous research, a trio of experimentally validated inflamma-miRs were considered: miR-155, miR-146a and miR-21. Our in silico study supports the hypothesis that these inflamma-miRs could modulate some pathways, such as lysine degradation and lengthening of fatty acids which are involved in the modulation of microbiota composition, i.e. prevotella, ruminococcus and oscillibacter and vice versa. Food homologues to human miR-21, miR-155 and miR-146a were found in cow fat, cow milk, and eggs suggesting that they may be able of targeting, and probably exacerbating, inflammation related pathways. If these data will be experimentally validated, they will further support the relevance of a nutraceutical approach for a healthy aging.

Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.

Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti-inflammatory and immune-regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium-treated mice. In particular, this agent significantly elevated the abundance of short-chain fatty acid (SCFA)-producing gut microbiota, causatively related with the enhanced development of Treg cells and the reduced proinflammatory Th17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA-producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.-Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.

N-(1-carbamoyl-2-phenylethyl) butyramide reduces antibiotic-induced intestinal injury, innate immune activation and modulates microbiota composition

The use/misuse of antibiotics leads to pathological features referring to antibiotic-induced intestinal injury (AIJ), a clinical issue that plays a prominent role in the development of severe digestive disturbances. AIJ is characterized by loss of intestinal architecture and function, dysbiosis and bacterial translocation into the liver, triggering hepatic inflammation. This study aimed at determining the beneficial effect of N-(1-carbamoyl-2-phenylethyl) butyramide (FBA), a butyrate releasing compound, in ceftriaxone-induced intestinal injury. To this purpose, mice receiving ceftriaxone (8 g∙kg−1/die, per os) for five days, were treated with FBA (212,5 mg∙kg−1/die, per os) for five or fifteen days. FBA modulated key players of innate immunity in antibiotic-injured gut tissues, reducing inflammatory process and improving the anti-inflammatory and resolving pattern. FBA also improved colonic architecture and intestinal integrity. Interestingly, we also observed a remodeling of gut microbiota composition related to an increase of metabolic pathways related to lactate and butyrate production. At mechanistic level, FBA induced histone acetylation and increased the expression of GPR43 and monocarboxylate transporter 1 in colon. Our data clearly demonstrated that FBA has multiple converging mechanisms in limiting intestinal and hepatic alterations to counteract AIJ.

Short-chain fructo-oligosaccharides enhances intestinal barrier function by attenuating mucosa inflammation and altering colonic microbiota composition of weaning piglets

Short-chain fructo-oligosaccharides (scFOS) exert beneficial effects on growth performance and immune function of piglets. However, the effects of scFOS on intestinal integrity of piglets remain to be understood. This study was conducted to investigate the protective effects of scFOS on the intestinal barrier function of piglets. A total of 16 castrated male piglets weaned at 28 d were randomly allocated into 1 of 2 dietary treatments (n = 8): a control diet (CON) or a scFOS-supplemented diet (4 g/kg scFOS substituted the same amount of maize in CON). The experiment lasted 28 d. The average daily scFOS intake of treated group was 1.94 g. Results showed that scFOS consumption increased average daily gain and decreased feed to gain ratio and diarrhoea index (p < .05). scFOS-fed piglets had lower serum D-lactate, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-α) concentrations than CON-fed piglets (p < .05). scFOS consumption increased intestinal expression of zona occludens 1 (ZO1), occluding (OCLN) and claudin 1 (CLDN1) (p < .05). scFOS supplementation down-regulated IL-1β expression in jejunal mucosa and IL-6 expression in ileal mucosa (p < .05). scFOS-fed piglets had higher acetic acid level in colonic chyme than their counterparts (p < .05). scFOS consumption increased relative abundances of Bacteroidetes, Lactobacillus spp., Prevotella spp. and Bifidobacterium spp. in colonic chyme (p < .05). In conclusion, post-weaning scFOS consumption improved performance and intestinal integrity of piglets by suppressing mucosal inflammation, increasing production of short-chain fatty acids and modulating microbiota composition in the hindgut.HighlightsDietary supplementation of 4 g/kg short-chain fructo-oligosaccharides (scFOS) improved growth performance of weaning piglets.Dietary scFOS inclusion enhanced gut integrity and ameliorated intestinal inflammatory response.scFOS consumption resulted in increased short-chain fatty acids production and altered microbiota composition in the hindgut of piglets.

Nourishing the gut microbiota: The potential of prebiotics in microbiota-gut-brain axis research

Abstract Dietary fiber and prebiotics consistently modulate microbiota composition and function and hence may constitute a powerful tool in microbiota-gut-brain axis research. However, this is largely ignored in Hooks et al.’s analysis, which highlights the limitations of probiotics in establishing microbiome-mediated effects on neurobehavioral functioning and neglects discussing the potential of prebiotics in warranting the microbiota's role in such effects.

Effect of combined bifidobacteria supplementation and resistance training on cognitive function, body composition and bowel habits of healthy elderly subjects.

Physical exercise exerts favourable effects on brain health and quality of life of the elderly; some of these positive health effects are induced by the modulation of microbiota composition. We therefore conducted a randomised, double blind, placebo-controlled trial that assessed whether a combination of Bifidobacterium spp. supplementation and moderate resistance training improved the cognitive function and other health-related parameters in healthy elderly subjects. Over a 12-week period, 38 participants (66-78 years) underwent resistance training and were assigned to the probiotic Bifidobacterium supplementation (n=20; 1.25×1010 cfu each of Bifidobacterium longum subsp. longum BB536, B. longum subsp. infantis M-63, Bifidobacterium breve M-16V and B. breve B-3) or the placebo (n=18) group. At baseline and at 12 weeks, we assessed the cognitive function, using the Japanese version of the Montreal Cognitive Assessment instrument (MoCA-J); modified flanker task scores; depression-anxiety scores; body composition; and bowel habits. At 12 weeks, the MoCA-J scores showed a significant increase in both the groups, while the flanker task scores of the probiotic group increased more significantly than those of the placebo group (0.35±0.9 vs -0.29±1.1, P=0.056). Only the probiotic group showed a significant decrease in the depression-anxiety scores (5.2±6.3 to 3.4±5.5, P=0.012) and body mass index (24.0±2.8 to 23.5±2.8 kg/m2, P<0.001), with a significant increase in the defecation frequency (5.3±2.3 to 6.4±2.3 times/5 days, P=0.023) at 12 weeks. Thus, in healthy elderly subjects, combined probiotic bifidobacteria supplementation and moderate resistance training may improve the mental condition, body weight and bowel movement frequency.

The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis.

The microbiota, the gut, and the brain communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (VN), the principal component of the parasympathetic nervous system, is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN, because of its role in interoceptive awareness, is able to sense the microbiota metabolites through its afferents, to transfer this gut information to the central nervous system where it is integrated in the central autonomic network, and then to generate an adapted or inappropriate response. A cholinergic anti-inflammatory pathway has been described through VN's fibers, which is able to dampen peripheral inflammation and to decrease intestinal permeability, thus very probably modulating microbiota composition. Stress inhibits the VN and has deleterious effects on the gastrointestinal tract and on the microbiota, and is involved in the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) which are both characterized by a dysbiosis. A low vagal tone has been described in IBD and IBS patients thus favoring peripheral inflammation. Targeting the VN, for example through VN stimulation which has anti-inflammatory properties, would be of interest to restore homeostasis in the microbiota-gut-brain axis.

Effect of dietary nucleosides and yeast extracts on composition and metabolic activity of infant gut microbiota in PolyFermS colonic fermentation models.

Nucleotides (NT) and nucleosides (NS) are added to infant formula to mimic the content of breast milk, but little is known about their impact on infant gut microbiota. In this study, we tested the effect of NS and of yeast extracts (YE) with different NT content using PolyFermS continuous fermentation models mimicking formula-fed, healthy and enteropathogen-contaminated infant gut microbiota. Microbiota composition, short-chain fatty acid (SCFA) formation and gene expression were determined. NS, and to a larger extend YE modulated microbiota composition and increased metabolic activity in both models. Anaerococcus, Peptoniphilus, Fusobacterium, Lactobacillus/Pediococcus/Leuconostoc and Veillonella were enhanced when YE and/or NS were added. The production of SCFA increased with the level of supplied NT equivalents. Addition of NS and YE reduced colonization of Salmonella compared to control periods. Gene expression analysis confirmed taxonomical changes and indicated functional responses to YE. Transcripts related to NT and sulfur metabolism and iron acquisition increased while biosynthesis of co-factors and vitamins decreased after YE addition. Elevated butyrate formation correlated with increased transcripts encoding key enzymes of the two major butyrate synthesis pathways. Our results uncover a strong dose-dependent modulation of NS and YE on infant gut microbiota composition and metabolic activity.

Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring’s birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease.

It has been hypothesized that alterations in the composition of the gut microbiota might be associated with the onset of certain human pathologies, such as Alzheimer disease, a neurodegenerative syndrome associated with cerebral accumulation of amyloid-β fibrils. It has been shown that bacteria populating the gut microbiota can release significant amounts of amyloids and lipopolysaccharides, which might play a role in the modulation of signaling pathways and the production of proinflammatory cytokines related to the pathogenesis of Alzheimer disease. Additionally, nutrients have been shown to affect the composition of the gut microbiota as well as the formation and aggregation of cerebral amyloid-β. This suggests that modulating the gut microbiome and amyloidogenesis through specific nutritional interventions might prove to be an effective strategy to prevent or reduce the risk of Alzheimer disease. This review examines the possible role of the gut in the dissemination of amyloids, the role of the gut microbiota in the regulation of the gut-brain axis, the potential amyloidogenic properties of gut bacteria, and the possible impact of nutrients on modulation of microbiota composition and amyloid formation in relation to the pathogenesis of Alzheimer disease.

Activation of Immune and Defense Responses in the Intestinal Mucosa by Outer Membrane Vesicles of Commensal and Probiotic Escherichia coli Strains.

The influence of microbiota in human health is well-known. Imbalances in microbiome structure have been linked to several diseases. Modulation of microbiota composition through probiotic therapy is an attempt to harness the beneficial effects of commensal microbiota. Although, there is wide knowledge of the responses induced by gut microbiota, the microbial factors that mediate these effects are not well-known. Gram-negative bacteria release outer membrane vesicles (OMVs) as a secretion mechanism of microbial factors, which have an important role in intercellular communication. Here, we investigated whether OMVs from the probiotic Escherichia coli strain Nissle 1917 (EcN) or the commensal E. coli strain ECOR12 trigger immune responses in various cellular models: (i) peripheral blood mononuclear cells (PBMCs) as a model of intestinal barrier disruption, (ii) apical stimulation of Caco-2/PMBCs co-culture as a model of intact intestinal mucosa, and (iii) colonic mucosa explants as an ex vivo model. Stimulations with bacterial lysates were also performed. Whereas, both OMVs and lysates activated expression and secretion of several cytokines and chemokines in PBMCs, only OMVs induced basolateral secretion and mRNA upregulation of these mediators in the co-culture model. We provide evidence that OMVs are internalized in polarized Caco-2 cells. The activated epithelial cells elicit a response in the underlying immunocompetent cells. The OMVs effects were corroborated in the ex vivo model. This experimental study shows that OMVs are an effective strategy used by beneficial gut bacteria to communicate with and modulate host responses, activating signaling events through the intestinal epithelial barrier.

Diet quality improves for parents and children when almonds are incorporated into their daily diet: a randomized, crossover study

The health benefits of nuts may, in part, be due to the fiber that provides substrate for the maintenance of a healthy and diverse microbiota. We hypothesized that consuming almonds would benefit immune status through improving diet quality and modulation of microbiota composition in parents and their children, while improving gastrointestinal function. In a crossover trial, 29 parents (35 ± 0.6 years) and their children (n = 29; 4 ± 0.2 years; pairs) consumed 1.5 and 0.5 oz, respectively, of almonds and/or almond butter or control (no almonds) for 3 weeks followed by 4-week washouts. Parents completed daily questionnaires of stool frequency and compliance with nut intake. The Gastrointestinal Symptom Response Scale was administered weekly. Participants provided stools for microbiota analysis and saliva for secretory immunoglobulin A. Serum antioxidant/proinflammatory balance was determined in parents. From weekly dietary recalls (Automated Self-Administered 24-Hour Dietary Recall), nutrient and energy intake were assessed and Healthy Eating Index-2010 scores were calculated. Consuming almonds increased total Healthy Eating Index score from 53.7 ± 1.8 to 61.4 ± 1.4 (parents) and 53.7 ± 2.6 to 61.4 ± 2.2 (children; P < .001). Minimal changes in gastrointestinal symptoms and no change in stool frequency were noted with the almond intervention. Microbiota was stable at the phylum and family level, but genus-level changes occurred with nut intake, especially in children. No differences were observed for immune markers. Although higher intakes of almonds or longer interventions may be needed to demonstrate effects on immune status, a moderate intake of almonds improves diet quality in adults and their young children and modulates microbiota composition.

The Role of Low FODMAP Diet in the Management of Irritable Bowel Syndrome

The Role of Low FODMAP Diet in the Management of Irritable Bowel Syndrome