The Microbiota–Gut–Brain Axis and Alzheimer’s Disease: Neuroinflammation Is to Blame?

For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota–gut–brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is determined by increase in the permeability of the gut barrier and immune cell activation, leading to impairment in the blood–brain barrier function that promotes neuroinflammation, neuronal loss, neural injury, and ultimately AD. Numerous studies have shown that the gut microbiota plays a crucial role in brain function and changes in the behavior of individuals and the formation of bacterial amyloids. Lipopolysaccharides and bacterial amyloids synthesized by the gut microbiota can trigger the immune cells residing in the brain and can activate the immune response leading to neuroinflammation. Growing experimental and clinical data indicate the prominent role of gut dysbiosis and microbiota–host interactions in AD. Modulation of the gut microbiota with antibiotics or probiotic supplementation may create new preventive and therapeutic options in AD. Accumulating evidences affirm that research on MGB involvement in AD is necessary for new treatment targets and therapies for AD.     

Microbiome as Mediator of Diet on Colorectal Cancer Risk: The Role of Vitamin D,Markers of Inflammation and Adipokines

Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case–control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk—increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of “healthy” intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process.     

Magnesium in Obesity,Metabolic Syndrome,and Type 2 Diabetes

Magnesium (Mg²⁺) deficiency is probably the most underestimated electrolyte imbalance in Western countries. It is frequent in obese patients, subjects with type-2 diabetes and metabolic syndrome, both in adulthood and in childhood. This narrative review aims to offer insights into the pathophysiological mechanisms linking Mg²⁺ deficiency with obesity and the risk of developing metabolic syndrome and type 2 diabetes. Literature highlights critical issues about the treatment of Mg²⁺ deficiency, such as the lack of a clear definition of Mg²⁺ nutritional status, the use of different Mg²⁺ salts and dosage and the different duration of the Mg²⁺ supplementation. Despite the lack of agreement, an appropriate dietary pattern, including the right intake of Mg²⁺, improves metabolic syndrome by reducing blood pressure, hyperglycemia, and hypertriglyceridemia. This occurs through the modulation of gene expression and proteomic profile as well as through a positive influence on the composition of the intestinal microbiota and the metabolism of vitamins B1 and D.     

Effects of a Rice Bran Dietary Intervention on the Composition of the Intestinal Microbiota of Adults with a High Risk of Colorectal Cancer: A Pilot Randomised-Controlled Trial

Rice bran exhibits chemopreventive properties that may help to prevent colorectal cancer (CRC), and a short-term rice bran dietary intervention may promote intestinal health via modification of the intestinal microbiota. We conducted a pilot, double-blind, randomised placebo-controlled trial to assess the feasibility of implementing a long-term (24-week) rice bran dietary intervention in Chinese subjects with a high risk of CRC, and to examine its effects on the composition of their intestinal microbiota. Forty subjects were randomised into the intervention group (n = 19) or the control group (n = 20). The intervention participants consumed 30 g of rice bran over 24-h intervals for 24 weeks, whilst the control participants consumed 30 g of rice powder on the same schedule. High rates of retention (97.5%) and compliance (≥91.3%) were observed. No adverse effects were reported. The intervention significantly enhanced the intestinal abundance of Firmicutes and Lactobacillus, and tended to increase the Firmicutes/Bacteroidetes ratio and the intestinal abundance of Prevotella_9 and the health-promoting Lactobacillales and Bifidobacteria, but had no effect on bacterial diversity. Overall, a 24-week rice bran dietary intervention was feasible, and may increase intestinal health by inducing health-promoting modification of the intestinal microbiota. Further larger-scale studies involving a longer intervention duration and multiple follow-up outcome assessments are recommended.     

Postbiotic Supplementation for Children and Newborn’s Health

It is now well known how the microbiota can positively or negatively influence humans health, depending on its composition. The microbiota’s countless beneficial effects have allowed it to be defined as a genuine symbiont for our species. In an attempt to positively influence the microbiota, research has focused on probiotics and prebiotics. Probiotics are viable beneficial bacteria of various strains. Prebiotics are specific substances able to favor the development of advantageous bacteria strains. Postbiotics are a new category of compounds capable of affecting the microbiota. According to the different definitions, postbiotics include both nonviable bacteria and substances deriving from bacterial metabolism. Postbiotics are particularly promising in pediatric settings, as they offer some advantages over probiotics, including the absence of the risk of intestinal translocation or worsening of local inflammation. For these reasons, their use in fragile population categories such as newborns, and even more prematures, seems to be the best solution for improving microbiota’s health in this population. This narrative review aims to collect the research conducted so far on postbiotics’ potential in the first stages of life.     

Colonic In Vitro Model Assessment of the Prebiotic Potential of Bread Fortified with Polyphenols Rich Olive Fiber

The use of olive pomace could represent an innovative and low-cost strategy to formulate healthier and value-added foods, and bakery products are good candidates for enrichment. In this work, we explored the prebiotic potential of bread enriched with Polyphenol Rich Fiber (PRF), a defatted olive pomace byproduct previously studied in the European Project H2020 EcoProlive. To this aim, after in vitro digestion, the PRF-enriched bread, its standard control, and fructo-oligosaccharides (FOS) underwent distal colonic fermentation using the in vitro colon model MICODE (multi-unit colon gut model). Sampling was done prior, over and after 24 h of fermentation, then metabolomic analysis by Solid Phase Micro Extraction Gas Chromatography Mass Spectrometry (SPME GCMS), 16S-rDNA genomic sequencing of colonic microbiota by MiSeq, and absolute quantification of main bacterial species by qPCR were performed. The results indicated that PRF-enriched bread generated positive effects on the host gut model: (i) surge in eubiosis; (ii) increased abundance of beneficial bacterial groups, such as Bifidobacteriaceae and Lactobacillales; (iii) production of certain bioactive metabolites, such as low organic fatty acids; (iv) reduction in detrimental compounds, such as skatole. Our study not only evidenced the prebiotic role of PRF-enriched bread, thereby paving the road for further use of olive by-products, but also highlighted the potential of the in vitro gut model MICODE in the critical evaluation of functionality of food prototypes as modulators of the gut microbiota.     

Ingestion of High β-Glucan Barley Flour Enhances the Intestinal Immune System of Diet-Induced Obese Mice by Prebiotic Effects

The prebiotic effect of high β-glucan barley (HGB) flour on the innate immune system of high-fat model mice was investigated. C57BL/6J male mice were fed a high-fat diet supplemented with HGB flour for 90 days. Secretory immunoglobulin A (sIgA) in the cecum and serum were analyzed by enzyme-linked immunosorbent assays (ELISA). Real-time PCR was used to determine mRNA expression levels of pro- and anti-inflammatory cytokines such as interleukin (IL)-10 and IL-6 in the ileum as well as the composition of the microbiota in the cecum. Concentrations of short-chain fatty acids (SCFAs) and organic acids were analyzed by GC/MS. Concentrations of sIgA in the cecum and serum were increased in the HGB group compared to the control. Gene expression levels of IL-10 and polymeric immunoglobulin receptor (pIgR) significantly increased in the HGB group. HGB intake increased the bacterial count of microbiota, such as Bifidobacterium and Lactobacillus. Concentrations of propionate and lactate in the cecum were increased in the HGB group, and a positive correlation was found between these organic acids and the IL-10 expression level. Our findings showed that HGB flour enhanced immune function such as IgA secretion and IL-10 expression, even when the immune system was deteriorated by a high-fat diet. Moreover, we found that HGB flour modulated the gut microbiota, which increased the concentration of SCFAs, thereby stimulating the immune system.     

Bifidobacterium adolescentis Isolated from Different Hosts Modifies the Intestinal Microbiota and Displays Differential Metabolic and Immunomodulatory Properties in Mice Fed a High-Fat Diet

The incidence of obesity, which is closely associated with the gut microbiota and chronic inflammation, has rapidly increased in the past 40 years. Therefore, the probiotic-based modification of the intestinal microbiota composition has been developed as a strategy for the treatment of obesity. In this study, we selected four Bifidobacterium adolescentis strains isolated from the feces of newborn and elderly humans to investigate whether supplementation with B. adolescentis of various origins could alleviate obesity in mice. Male C57BL/6J mice fed a high-fat diet (HFD, 60% energy as fat) received one of the following 14-week interventions: (i) B. adolescentis N4_N3, (ii) B. adolescentis Z25, (iii) B. adolescentis 17_3, (iv) B. adolescentis 2016_7_2, and (v) phosphate-buffered saline. The metabolic parameters, thermogenesis, and immunity of all treated mice were measured. Cecal and colonic microbial profiles were determined by 16S rRNA gene sequencing. Intestinal concentrations of short-chain fatty acids (SCFAs) were measured by gas chromatography-mass spectrometry (GC-MS). The B. adolescentis strains isolated from the feces of elderly humans (B. adolescentis Z25, 17_3, and 2016_7_2) decreased the body weight or weight gain of mice, whilst the strain isolated from the newborn (B. adolescentis N4_N3) increased the body weight of mice. The B. adolescentis strains isolated from the elderly also increased serum leptin concentrations and induced the expression of thermogenesis- and lipid metabolism-related genes in brown adipose tissue. All the B. adolescentis strains alleviated inflammations in the spleen and brain and modified the cecal and colonic microbiota. Particularly, all strains reversed the HFD-induced depletion of Bifidobacterium and reduced the development of beta-lactam resistance. In addition, the B. adolescentis strains isolated from the elderly increased the relative abundances of potentially beneficial genera, such as Bacteroides, Parabacteroides, and Faecalibaculum. We speculate that such increased abundance of commensal bacteria may have mediated the alleviation of obesity, as B. adolescentis supplementation decreased the intestinal production of SCFAs, thereby reducing energy delivery to the host mice. Our results revealed that certain strains of B. adolescentis can alleviate obesity and modify the gut microbiota of mice. The tested strains of B. adolescentis showed different effects on lipid metabolism and immunity regulation, with these effects related to whether they had been isolated from the feces of newborn or elderly humans. This indicates that B. adolescentis from different sources may have disparate effects on host health possibly due to the transmission of origin-specific functions to the host.     

Effects of Anthocyanin on Intestinal Health: A Systematic Review

Intestinal health relies on the association between the mucosal immune system, intestinal barrier and gut microbiota. Bioactive components that affect the gut microbiota composition, epithelial physical barrier and intestinal morphology were previously studied. The current systematic review evaluated evidence of anthocyanin effects and the ability to improve gut microbiota composition, their metabolites and parameters of the physical barrier; this was conducted in order to answer the question: “Does food source or extract of anthocyanin promote changes on intestinal parameters?”. The data analysis was conducted following the PRISMA guidelines with the search performed at PubMed, Cochrane and Scopus databases for experimental studies, and the risk of bias was assessed by the SYRCLE tool. Twenty-seven studies performed in animal models were included, and evaluated for limitations in heterogeneity, methodologies, absence of information regarding allocation process and investigators’ blinding. The data were analyzed, and the anthocyanin supplementation demonstrated positive effects on intestinal health. The main results identified were an increase of Bacteroidetes and a decrease of Firmicutes, an increase of short chain fatty acids production, a decrease of intestinal pH and intestinal permeability, an increase of the number of goblet cells and tight junction proteins and villi improvement in length or height. Thus, the anthocyanin supplementation has a potential effect to improve the intestinal health. PROSPERO (CRD42020204835).