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Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition associated with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies NAFLD, the current nomenclature has been revised, and the term metabolic-associated fatty liver disease (MAFLD) has been proposed. The new definition emphasizes the bidirectional relationships and increases awareness in looking for fatty liver disease among patients with T2DM and CVD or its risk factors, as well as looking for these diseases among patients with NAFLD. The most recommended treatment method of NAFLD is lifestyle changes, including dietary fructose limitation, although other treatment methods of NAFLD have recently emerged and are being studied. Given the focus on the liver–gut axis targeting, bacteria may also be a future aim of NAFLD treatment given the microbiome signatures discriminating healthy individuals from those with NAFLD. In this review article, we will provide an overview of the associations of fructose consumption, gut microbiota, diabetes, and CVD in patients with NAFLD.

Gut microbiota dysbiosis is strongly associated with psychiatric disorders and inflammatory bowel disease (IBD). Herein, we examined whether the fecal microbiota of IBD patients with depression (IBDD) and their gut microbiota culture (iGm) could cause depression and colitis in mice and anti-inflammatory probiotics could mitigate depression in iGm-transplanted or immobilization stress (IS)-exposed mice. Fecal microbiota transplantation (FMT) from IBDD patients, which exhibited Enterobacteriaceae-rich gut microbiota, and its gut microbiota culture (iGm) increased depression-like behaviors in mice. Their treatments heightened the blood lipopolysaccharide (LPS) level and colonic IL-1β and IL-6 expression. However, FMT from healthy volunteers or sulfasalazine treatment alleviated cGm-induced depressive-like behaviors and hippocampal and colonic inflammation in mice. Moreover, oral administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175, which inhibited LPS-induced IL-6 expression in macrophages, alleviated cGm-induced depression-like behaviors, hippocampal NF-κB+Iba1+ cell numbers and IL-1β and IL-6 expression, blood LPS, IL-6, and creatinine levels, and colonic NF-κB+CD11c+ number and IL-1β and IL-6 expression in mice. Treatment with NK151, NK173, or NK175 mitigated immobilization stress (IS)-induced depressive-like behaviors, neuroinflammation, and gut inflammation in mice. NK151, NK173, or NK175 also decreased IS-induced blood LPS, IL-6, and creatinine levels. The transplantation of Enterobacteriaceae-rich gut microbiota can cause depression and colitis, as IS exposure, and anti-inflammatory NK151, NK173, and NK175, may alleviate stress-induced fatigue, depression, and colitis by regulating the expression of proinflammatory and anti-inflammatory cytokines through the suppression of gut bacterial LPS.

Cannabidiol (CBD) is widely available and marketed as having therapeutic properties. Over-the-counter CBD is unregulated, many of the therapeutic claims lack scientific support, and controversy exists as to the safety of CBD-liver interaction. The study aims were to compare the pharmacokinetics of commercial CBD and CBD metabolites following the ingestion of five different CBD formulations, determine the influence of CBD on food induced thermogenesis, determine the influence of food on CBD pharmacokinetics, and determine the influence of CBD on markers of liver function. Fourteen males (body mass index ≥ 25 kg/m2) were studied in a placebo-controlled, randomized, crossover design. On five occasions, different CBD formulations were ingested (one per visit). On two additional occasions, CBD or placebo was ingested following a meal. CBD servings were standardized to 30 mg. Considerable pharmacokinetic variability existed between formulations; this pharmacokinetic variability transferred to several of the metabolites. CBD did not influence food induced thermogenesis but did favorably modify early insulin and triglyceride responses. Food appreciably altered the pharmacokinetics of CBD. Finally, CBD did not evoke physiologically relevant changes in markers of liver function. Collectively, these data suggest that consumers should be aware of the appreciable pharmacokinetic differences between commercial CBD formulations, CBD is unlikely to influence the caloric cost of eating but may prove to be of some benefit to initial metabolic responses, consuming CBD with food alters the dynamics of CBD metabolism and increases systemic availability, and low-dose CBD probably does not represent a risk to normal liver function.

Oral cannabidiol (CBD) consumption is widespread in North America and Europe, as it has analgesic, neuroprotective and antitumor effects. Although oral CBD consumption in humans affords beneficial effects in epileptic and inflammatory states, its pharmacokinetics and subsequent uptake into tissue are largely unknown. This study investigated plasma pharmacokinetics and accumulation of CBD in gastrocnemius muscle, liver and adipose tissue in adult rats following oral gavage. CBD was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males and 6 females per dosing group. Pharmacokinetics were assessed on day 1 and day 28 in the group receiving CBD at 115 mg/Kg/day. The rise in tissue CBD was closely related to specific pharmacokinetic parameters, and adipose tissue levels were ~10 to ~100 fold greater than liver or muscle. Tissue CBD levels were moderately correlated between adipose and muscle, and adipose and liver, but were highly correlated for liver and muscle. CBD feeding resulted in several gender-specific effects, including changes in pharmacokinetics, relationships between pharmacokinetic parameters and tissue CBD and differences in tissue CBD levels. CBD accumulation in mammalian tissues has the potential to influence receptor binding and metabolism; therefore, the present findings may have relevance for developing oral dosing regimens.

Harboring various proteins, lipids, and RNAs, the extracellular vesicles (EVs) in milk exert vital tissue-specific immune-protective functions in neonates via these bioactive cargos. This study aims to explore the anti-inflammatory effects of bovine milk-derived EVs on a dextran sulfate sodium (DSS)-induced colitis model and to determine the underlying molecular mechanisms. Sixty C57BL/6 mice were divided into the NC group (normal control), DSS group (DSS + PBS), DSS + LOW group (DSS + 1.5 × 108 p/g EVs), DSS + MID group (DSS + 1.5 × 109 p/g EVs), and DSS + HIG group (DSS + 1.0 × 1010 p/g EVs). Histopathological sections, the gut microbiota, and intestinal tissue RNA-Seq were used to comprehensively evaluate the beneficial functions in mitigating colitis. The morphology exhibited that the milk-derived EVs contributed to the integrity of the superficial epithelial structure in the intestine. Additionally, the concentrations of IL-6 and TNF-α in the colon tissues were significantly decreased in the EVs-treated mice. The abundances of the Dubosiella, Bifidobacterium, UCG-007, Lachnoclostridium, and Lachnospiraceae genera were increased in the gut after treatment with the milk-derived EVs. Additionally, the butyrate and acetate production were enriched in feces. In addition, 1659 genes were significantly down-regulated and 1981 genes were significantly up-regulated in the EVs-treated group. Meanwhile, 82 lncRNAs and 6 circRNAs were also differentially expressed. Overall, the milk-derived EVs could attenuate colitis through optimizing gut microbiota abundance and by manipulating intestinal gene expression, implying their application potential for colitis prevention.

Previous studies showed that diet and gut microbiota had a correlation with sleep. However, the potential interaction effects of diet and gut microbiota on sleep are still unclear. The phenotypic data of insomnia (including 374,505 subjects) and sleep duration (including 372,805 subjects) were obtained from the UK Biobank cohort. The Single Nucleotide Polymorphisms (SNPs) associated with 114 gut microbiota, 84 dietary habits, and 4 dietary compositions were derived from the published Genome-wide Association Study (GWAS). We used Linkage Disequilibrium Score Regression (LDSC) to estimate the genetic correlation and colocalization analysis to assess whether dietary habits and insomnia/sleep duration shared a causal variant in a region of the genome. Using UK Biobank genotype data, the polygenetic risk score of gut microbiota, dietary habits, and dietary compositions were calculated for each subject. Logistic regression and linear regression models were used to assess the potential effects of diet-gut microbiota interactions on sleep phenotypes, including insomnia and sleep duration. Insomnia and sleep duration were used as dependent variables, and sex, age, the Townsend Deprivation Index scores, and smoking and drinking habits were selected as covariates in the regression analysis. All statistical analyses were conducted using R-3.5.1 software. Significant genetic correlations were discovered between insomnia/sleep duration and dietary habits. Further, we found several significant dietary compositions-gut microbiota interactions associated with sleep, such as fat × G_Collinsella_RNT (p = 1.843 × 10−2) and protein × G_Collinsella_HB (p = 7.11 × 10−3). Besides, multiple dietary habits-gut microbiota interactions were identified for sleep, such as overall beef intake × G_Desulfovibrio_RNT (p = 3.26 × 10−4), cups of coffee per day × G_Escherichia_Shigella_RNT (p = 1.14 × 10−3), and pieces of dried fruit per day × G_Bifidobacterium_RNT (p = 5.80 × 10−3). This study reported multiple diet-gut microbiota interactions associated with sleep, which may provide insights into the biological mechanisms of diet and gut microbiota affecting sleep.

The gut microbiota has been shown in recent years to be involved in the development and severity of type 2 diabetes (T2D). The aim of the present study was to test the effect of a 2-week functional food intervention on the gut microbiota composition in prediabetic individuals. A randomized double-blind, cross-over trial was conducted on prediabetic subjects. Fifteen volunteers were provided products made of: (i) 50% taro flour + 50% wheat flour; (ii) these products and the probiotic L. plantarum IS-10506; or (iii) these products with beetroot adsorbed for a period of 2 weeks with 2 weeks wash-out in between. Stool and blood samples were taken at each baseline and after each of the interventions. The gut microbiota composition was evaluated by sequencing the V3–V4 region of the 16S rRNA gene and anthropometric measures were recorded. The total weight loss over the entire period ranged from 0.5 to 11 kg. The next-generation sequencing showed a highly personalized microbiota composition. In the principal coordinate analyses, the samples of each individual clustered closer together than the samples of each treatment. For six individuals, the samples clustered closely together, indicating a stable microbiota. For nine individuals, the microbiota was less resilient and, depending on the intervention, the beta-diversity transiently differed greatly only to return to the composition close to the baseline during the wash-out. The statistical analyses showed that 202 of the total 304 taxa were significantly different between the participants. Only Butyricimonas could be correlated with taro ingestion. The results of the study show that the highly variable interindividual variation observed in the gut microbiota of the participants clouded any gut microbiota modulation that might be present due to the functional food interventions.

International audience; Abstract: The human gut microbiota is currently the focus of converging interest in many diseasesand sports performance. This review presents gut microbiota as a real “orchestra conductor” in thehost’s physio(patho)logy due to its implications in many aspects of health and disease. Reciprocally,gut microbiota composition and activity are influenced by many different factors, such as diet andphysical activity. Literature data have shown that macro- and micro-nutrients influence gut microbiotacomposition. Cumulative data indicate that gut bacteria are sensitive to modulation by physicalactivity, as shown by studies using training and hypoactivity models. Sports performance studieshave also presented interesting and promising results. Therefore, gut microbiota could be considered a“pivotal” organ for health and sports performance, leading to a new concept: the nutrition-microbiotaphysical activity triad. The next challenge for the scientific and medical communities is to test thisconcept in clinical studies. The long-term aim is to find the best combination of the three elementsof this triad to optimize treatments, delay disease onset, or enhance sports performance. The manypossibilities offered by biotic supplementation and training modalities open different avenues forfuture research

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation is implicated in the pathogenesis of several gastrointestinal and extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through the increasingly defined gut microbiota brain axis, opening the possibility for new microbiota-based therapeutic options. Although several studies have been conducted to unravel the possible relationship between Alzheimer’s Disease (AD) pathogenesis and progression, the diagnostic and therapeutic potential of approaches aiming at restoring gut microbiota eubiosis remain to be fully addressed. In this narrative review, we briefly summarize the role of gut microbiota homeostasis in brain health and disease, and we present evidence for its dysregulation in AD patients. Based on these observations, we then discuss how dysbiosis might be exploited as a new diagnostic tool in early and advanced disease stages, and we examine the potential of prebiotics, probiotics, fecal microbiota transplantation, and diets as complementary therapeutic interventions on disease pathogenesis and progression, thus offering new insights into the diagnosis and treatment of this devastating and progressive disease.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.

It can be assumed that changes in the gut microbiota play a crucial role in the development of type 2 diabetes mellitus (T2DM). It is generally accepted that regular physical activity is beneficial for the prevention and therapy of T2DM. Therefore, this review analyzes the effects of exercise training on the gut microbiota composition and the intestinal barrier function in T2DM. The current literature shows that regular exercise can influence the gut microbiota composition and the intestinal barrier function with ameliorative effects on T2DM. In particular, increases in the number of short-chain fatty acid (SCFA)-producing bacteria and improvements in the gut barrier integrity with reduced endotoxemia seem to be key points for positive interactions between gut health and T2DM, resulting in improvements in low-grade systemic inflammation status and glycemic control. However, not all aspects are known in detail and further studies are needed to further examine the efficacy of different training programs, the role of myokines, SCFA-producing bacteria, and SCFAs in the relevant metabolic pathways. As microbial signatures differ in individuals who respond differently to exercise training programs, one scientific focus could be the development of computer-based methods for the personalized analysis of the gut microbiota in the context of a microbiota/microbiome-based training program.

The gut microbiota is a complex community of microorganisms that has become a new focus of attention due to its association with numerous human diseases. Research over the last few decades has shown that the gut microbiota plays a considerable role in regulating intestinal homeostasis, and disruption to the microbial community has been linked to chronic disease conditions such as inflammatory bowel disease (IBD), colorectal cancer (CRC), and obesity. Obesity has become a global pandemic, and its prevalence is increasing worldwide mostly in Western countries due to a sedentary lifestyle and consumption of high-fat/high-sugar diets. Obesity-mediated gut microbiota alterations have been associated with the development of IBD and IBD-induced CRC. This review highlights how obesity-associated dysbiosis can lead to the pathogenesis of IBD and CRC with a special focus on mechanisms of altered absorption of short-chain fatty acids (SCFAs).

The effect of diet on the composition of gut microbiota and the consequent impact on disease risk have been of expanding interest. The present review focuses on current insights of changes associated with dietary protein-induced gut microbial populations and examines their potential roles in the metabolism, health, and disease of animals. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol was used, and 29 highly relevant articles were obtained, which included 6 mouse studies, 7 pig studies, 15 rat studies, and 1 in vitro study. Analysis of these studies indicated that several factors, such as protein source, protein content, dietary composition (such as carbohydrate content), glycation of protein, processing factors, and protein oxidation, affect the digestibility and bioavailability of dietary proteins. These factors can influence protein fermentation, absorption, and functional properties in the gut and, consequently, impact the composition of gut microbiota and affect human health. While gut microbiota can release metabolites that can affect host physiology either positively or negatively, the selection of quality of protein and suitable food processing conditions are important to have a positive effect of dietary protein on gut microbiota and human health.

The microbiota–gut–brain axis is a bidirectional communication pathway that enables the gut microbiota to communicate with the brain through direct and indirect signaling pathways to influence brain physiology, function, and even behavior. Research has shown that probiotics can improve several aspects of health by changing the environment within the gut, and several lines of evidence now indicate a beneficial effect of probiotics on mental and brain health. Such evidence has prompted the arrival of a new term to the world of biotics research: psychobiotics, defined as any exogenous influence whose effect on mental health is bacterially mediated. Several taxonomic changes in the gut microbiota have been reported in neurodevelopmental disorders, mood disorders such as anxiety and depression, and neurodegenerative disorders such as Alzheimer’s disease. While clinical evidence supporting the role of the gut microbiota in mental and brain health, and indeed demonstrating the beneficial effects of probiotics is rapidly accumulating, most of the evidence to date has emerged from preclinical studies employing different animal models. The purpose of this review is to focus on the role of probiotics and the microbiota–gut–brain axis in relation to mood disorders and to review the current translational challenges from preclinical to clinical research.

Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.

Maternal metabolic disorder during early pregnancy may give rise to emotional and behavioral disorders in the child, vulnerable to bullying. Placental tryptophan fluctuation consequently disrupts offspring gut microbiome and brain neurogenesis with long-lasting physiological and social behavioral impacts. The aim of this study was to examine the hypothesis that the excess gestational tryptophan may affect children’s mental and physical development via modifying the microbiota-gut-brain axis, which lays the foundation of their mental status. Chicken embryo was employed due to its robust microbiota and independence of maternal influences during embryogenesis. The results indicated that embryonic tryptophan exposure reduced body weight and aggressiveness in the male offspring before and during adolescence. Additionally, the relative gut length and crypt depth were increased, while the villus/crypt ratio was decreased in tryptophan treated roosters, which was corresponding to the changes in the cecal microbiota composition. Furthermore, the catecholamine concentrations were increased in tryptophan group, which may be associated with the alterations in the gut microbiome and the gut-brain axis’s function. These changes may underlie the sociometric status of bullying; clarify how gestational tryptophan fluctuation compromises bullying and provide a strategy to prevent bullying by controlling dietary tryptophan and medication therapy during pregnancy.

Recent interest in the gut-brain-axis has highlighted the potential of prebiotics to impact wellbeing, and to affect behavioral change in humans. In this clinical trial, we examined the impact of four-weeks daily supplementation of galacto-oligosaccharides (GOS) on self-reported nutrient intake and relationships on gut microbiota in a four-week two-armed parallel double-blind placebo controlled GOS supplement trial in young adult females. Food diaries and stool samples were collected prior to and following 28 days of supplement consumption. It was found that four weeks of GOS supplementation influenced macronutrient intake, as evident by reduced carbohydrate and sugars and increased fats intake. Further analysis showed that the reduction in carbohydrates was predicted by increasing abundances of Bifidobacterium in the GOS group in comparison to the placebo group. This suggests that Bifidobacterium increase via GOS supplementation may help improve the gut microbiota composition by altering the desire for specific types of carbohydrates and boosting Bifidobacterium availability when fiber intake is below recommended levels, without compromising appetite for fiber from food.

Gluten-induced T-cell-mediated immune response damages the villous structure that significantly affects the functioning of the small intestinal mucosa [...]

Gut microbiota changes correlate with health status. Literature data on gut microbiota show that all dietary changes can induce the alteration of gut microbiota composition. Mediterranean diet (MD) is associated with a reduction of all-cause mortality and in this review, we analyzed its interactions with human microbiota. In particular, we explored the modulation of the human microbiota, in response to MD adherence, focusing the attention on polyphenols, polyunsaturated fatty acids (PUFA) ω-3 and fiber. Evidences suggest that MD is able to modulate the gut microbiota, increasing its diversity. In fact, a Mediterranean-type dietary pattern is associated with specific gut microbiota characteristics. The available evidence, suggests that gut microbiota of subjects that follow a MD is signif­icantly different from subjects that follow a Western diet model. In fact, the latter show an increased gut permeability, which is responsible for metabolic endotoxemia. For this reason, we can speculate that the gut microbiota of the subjects following a MD is able to prevent the onset of chronic non-communicable degenerative diseases, such as cardiovascular diseases and some types of cancer. However, in order to understand these correlations with dietary patterns, controlled intervention studies on the gut microbiota composition and activity are needed.

Premature infants have a fragile ecology of the gut microbiota, which is associated with many health problems and may be influenced by formula versus breast feeding. The present study investigated differences in the process of gut microbiota colonisation in preterm infants fed with breastmilk or formula with or without probiotics before 12 weeks. This cohort study recruited 138 premature infants, 31 in the breastmilk (BM) group, 59 in the probiotics formula (PF) group and 48 in the non-probiotics formula (NPF) group, according to the feeding practice they received at birth. Gut bacterial composition was identified with 16S rRNA gene sequencing in faecal samples collected at 1 week, 6 weeks and 12 weeks after birth. The alpha diversity was higher in the PF group compared to the other groups at week 1 and 6 (both p &lt, 0.01) but showed no difference at week 12. The beta diversity of the three groups showed a trend towards similarity at the first two stages (p &lt, 0.001 and p = 0.009, respectively) and finally showed no difference at week 12. Canonical redundancy analysis showed that feeding type could explain the difference in gut microbiota composition at week one and six (both p &lt, 0.01). At genus level, Bifidobacterium was enriched in the PF group, while the Enterococcus and Streptococcus was enriched in the NPF group. In summary, formula with probiotics feeding after birth can affect gut microbiota colonisation and lead to a bacterial community with less potential pathogens.

This cross-sectional study aimed to clarify the characteristic gut microbiota of Japanese patients with type 2 diabetes (T2DM) using t-distributed stochastic neighbor embedding analysis and the k-means method and to clarify the relationship with background data, including dietary habits. The gut microbiota data of 383 patients with T2DM and 114 individuals without T2DM were classified into red, blue, green, and yellow groups. The proportions of patients with T2DM in the red, blue, green, and yellow groups was 86.8% (112/129), 69.8% (81/116), 76.3% (90/118), and 74.6% (100/134), respectively, the red group had the highest prevalence of T2DM. There were no intergroup differences in sex, age, or body mass index. The red group had higher percentages of the Bifidobacterium and Lactobacillus genera and lower percentages of the Blautia and Phascolarctobacterium genera. Higher proportions of patients with T2DM in the red group used α-glucosidase inhibitors and glinide medications and had a low intake of fermented soybean foods, including miso soup, than those in the other groups. The gut microbiota pattern of the red group may indicate characteristic changes in the gut microbiota associated with T2DM in Japan. These results also suggest that certain diabetes drugs and fermented foods may be involved in this change. Further studies are needed to confirm the relationships among traditional dietary habits, the gut microbiota, and T2DM in Japan.

The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient, MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD+) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.

The metaproteome profiling of cecal contents collected from neonatal piglets fed pasteurized human milk (HM) or a dairy-based infant formula (MF) from postnatal day (PND) 2 to 21 were assessed. At PND 21, a subset of piglets from each group (n = 11/group) were euthanized, and cecal contents were collected for further metaproteome analysis. Cecal microbiota composition showed predominantly more Firmicutes phyla and Lachnospiraceae family in the lumen of cecum of HM-fed piglets in comparison to the MF-fed group. Ruminococcus&nbsp, gnavus was the most abundant species from the Firmicutes phyla in the cecal contents of the HM-fed piglets at 21 days of age. A greater number of expressed proteins were identified in the cecal contents of the HM-fed piglets relative to the MF-fed piglets. Greater abundances of proteins potentially expressed by Bacteroides spp. such as glycoside enzymes were noted in the cecal lumen of HM-fed piglets relative to the MF. Additionally, lyases associated with Lachnospiraceae family were abundant in the cecum of the HM group relative to the MF group. Overall, our findings indicate that neonatal diet impacts the gut bacterial taxa and microbial proteins prior to weaning. The metaproteomics data were deposited into PRIDE, PXD025432 and 10.6019/PXD025432.

Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2′-O-fucosyllactose and lacto-N-neotetraose (2′FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2′FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (β-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2′FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2′FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2′FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2′FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.

The gut microbiota is a crucial factor in maintaining homeostasis. The presence of commensal microorganisms leads to the stimulation of the immune system and its maturation. In turn, dysbiosis with an impaired intestinal barrier leads to accelerated contact of microbiota with the host’s immune cells. Microbial structural parts, i.e., pathogen-associated molecular patterns (PAMPs), such as flagellin (FLG), peptidoglycan (PGN), lipoteichoic acid (LTA), and lipopolysaccharide (LPS), induce inflammation via activation of pattern recognition receptors. Microbial metabolites can also develop chronic low-grade inflammation, which is the cause of many metabolic diseases. This article aims to systematize information on the influence of microbiota on chronic inflammation and the benefits of microbiota modification through dietary changes, prebiotics, and probiotic intake. Scientific research indicates that the modification of the microbiota in various disease states can reduce inflammation and improve the metabolic profile. However, since there is no pattern for a healthy microbiota, there is no optimal way to modify it. The methods of influencing microbiota should be adapted to the type of dysbiosis. Although there are studies on the microbiota and its effects on inflammation, this subject is still relatively unknown, and more research is needed in this area.

Background: Protein intake has been associated with the development of pre-diabetes (pre-T2D) and type 2 diabetes (T2D). The gut microbiota has the capacity to produce harmful metabolites derived from dietary protein. Furthermore, both the gut microbiota composition and metabolic status (e.g., insulin resistance) can be modulated by diet and ethnicity. However, to date most studies have predominantly focused on carbohydrate and fiber intake with regards to metabolic status and gut microbiota composition. Objectives: To determine the associations between dietary protein intake, gut microbiota composition, and metabolic status in different ethnicities. Methods: Separate cross-sectional analysis of two European cohorts (MetaCardis, n = 1759, HELIUS, n = 1528) including controls, patients with pre-T2D, and patients with T2D of Caucasian/non-Caucasian origin with nutritional data obtained from Food Frequency Questionnaires and gut microbiota composition. Results: In both cohorts, animal (but not plant) protein intake was associated with pre-T2D status and T2D status after adjustment for confounders. There was no significant association between protein intake (total, animal, or plant) with either gut microbiota alpha diversity or beta diversity, regardless of ethnicity. At the species level, we identified taxonomical signatures associated with animal protein intake that overlapped in both cohorts with different abundances according to metabolic status and ethnicity. Conclusions: Animal protein intake is associated with pre-T2D and T2D status but not with gut microbiota beta or alpha diversity, regardless of ethnicity. Gut microbial taxonomical signatures were identified, which could function as potential modulators in the association between dietary protein intake and metabolic status.

Pectin, a soluble fiber, improves non-alcoholic fatty-liver disease (NAFLD), but its mechanisms are unclear. We aimed to investigate the role of pectin-induced changes in intestinal microbiota (IM) in NAFLD. We recovered the IM from mice fed a high-fat diet, treated or not with pectin, to perform a fecal microbiota transfer (FMT). Mice fed a high-fat diet, which induces NAFLD, were treated with pectin or received a fecal microbiota transfer (FMT) from mice treated with pectin before (preventive FMT) or after (curative FMT) being fed a high-fat diet. Pectin prevented the development of NAFLD, induced browning of adipose tissue, and modified the IM without increasing the abundance of proteobacteria. Preventive FMT also induced browning of white adipose tissue but did not improve liver steatosis, in contrast to curative FMT, which induced an improvement in steatosis. This was associated with an increase in the concentration of short-chain fatty acids (SCFAs), in contrast to preventive FMT, which induced an increase in the concentration of branched SCFAs. Overall, we show that the effect of pectin may be partially mediated by gut bacteria.

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid–gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.

Background: High-fat diet (HFD) consumption induced gut dysbiosis, inflammation, obese-insulin resistance. Perilla seed oil (PSO) is a rich source of omega-3 polyunsaturated fatty acids with health promotional effects. However, the effects of PSO on gut microbiota/inflammation and metabolic disturbance in HFD-induced obesity have not been investigated. Therefore, we aimed to compare the effects of different doses of PSO and metformin on gut microbiota/inflammation, and metabolic parameters in HFD-fed rats. Methods: Thirty-six male Wistar rats were fed either a normal diet or an HFD for 24 weeks. At week 13, HFD-fed rats received either 50, 100, and 500 mg/kg/day of PSO or 300 mg/kg/day metformin for 12 weeks. After 24 weeks, the metabolic parameters, gut microbiota, gut barrier, inflammation, and oxidative stress were determined. Results: HFD-fed rats showed gut dysbiosis, gut barrier disruption with inflammation, increased oxidative stress, metabolic endotoxemia, and insulin resistance. Treatment with PSO and metformin not only effectively attenuated gut dysbiosis, but also improved gut barrier integrity and decreased gut inflammation. PSO also decreased oxidative stress, metabolic endotoxemia, and insulin resistance in HFD-fed rats. Metformin had greater benefits than PSO. Conclusion: PSO and metformin had the beneficial effect on attenuating gut inflammation and metabolic disturbance in obese-insulin resistance.

Background: Protein intake has been associated with the development of pre-diabetes (pre-T2D) and type 2 diabetes (T2D). The gut microbiota has the capacity to produce harmful metabolites derived from dietary protein. Furthermore, both the gut microbiota composition and metabolic status (e.g., insulin resistance) can be modulated by diet and ethnicity. However, to date most studies have predominantly focused on carbohydrate and fiber intake with regards to metabolic status and gut microbiota composition. Objectives: To determine the associations between dietary protein intake, gut microbiota composition, and metabolic status in different ethnicities. Methods: Separate cross-sectional analysis of two European cohorts (MetaCardis, n = 1759; HELIUS, n = 1528) including controls, patients with pre-T2D, and patients with T2D of Caucasian/non-Caucasian origin with nutritional data obtained from Food Frequency Questionnaires and gut microbiota composition. Results: In both cohorts, animal (but not plant) protein intake was associated with pre-T2D status and T2D status after adjustment for confounders. There was no significant association between protein intake (total, animal, or plant) with either gut microbiota alpha diversity or beta diversity, regardless of ethnicity. At the species level, we identified taxonomical signatures associated with animal protein intake that overlapped in both cohorts with different abundances according to metabolic status and ethnicity. Conclusions: Animal protein intake is associated with pre-T2D and T2D status but not with gut microbiota beta or alpha diversity, regardless of ethnicity. Gut microbial taxonomical signatures were identified, which could function as potential modulators in the association between dietary protein intake and metabolic status.

Metabolic diseases are serious threats to public health and related to gut microbiota. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are powerful regulators of gut microbiota, thus possessing prospects for preventing metabolic diseases. Therefore, the effects and mechanisms of PPSP on metabolic diseases targeting gut microbiota are worth discussing and clarifying. Generally, PPSP benefit metabolic diseases management, especially obesity and type 2 diabetes mellitus. The underlying gut microbial-related mechanisms are mainly the modulation of gut microbiota composition, regulation of gut microbial metabolites, and improvement of intestinal barrier function. Moreover, clinical trials showed the benefits of PPSP on patients with metabolic diseases, while the clinical strategies for gestational diabetes mellitus, optimal formula of synbiotics and health benefits of postbiotics need further study. This review fully summarizes the relationship between probiotics, prebiotics, synbiotics, postbiotics, and metabolic diseases, presents promising results and the one in dispute, and especially attention is paid to illustrates potential mechanisms and clinical effects, which could contribute to the next research and development of PPSP.

(1) Background: The use of antibiotics affects the composition of gut microbiota. Studies have suggested that the colonization of gut microbiota in early life is related to later food allergies. Still, the relationship between altered intestinal microbiota in adulthood and food allergies is unclear. (2) Methods: We established three mouse models to analyze gut microbiota dysbiosis’ impact on the intestinal barrier and determine whether this effect can increase the susceptibility to and severity of food allergy in later life. (3) Results: The antibiotic-induced gut microbiota dysbiosis significantly reduced Lachnospiraceae, Muribaculaceae, and Ruminococcaceae, and increased Enterococcaceae and Clostridiales. At the same time, the metabolic abundance was changed, including decreased short-chain fatty acids and tryptophan, as well as enhanced purine. This change is related to food allergies. After gut microbiota dysbiosis, we sensitized the mice. The content of specific IgE and IgG1 in mice serum was significantly increased, and the inflammatory response was enhanced. The dysbiosis of gut microbiota caused the sensitized mice to have more severe allergic symptoms, ruptured intestinal villi, and a decrease in tight junction proteins (TJs) when re-exposed to the allergen. (4) Conclusions: Antibiotic-induced gut microbiota dysbiosis increases the susceptibility and severity of food allergies. This event may be due to the increased intestinal permeability caused by decreased intestinal tight junction proteins and the increased inflammatory response.

Nowadays, caffeine is one of the most commonly consumed substances, which presents in many plants and products. It has both positive and negative effects on the human body, and its activity concerns a variety of systems including the central nervous system, immune system, digestive system, respiratory system, urinary tract, etc. These effects are dependent on quantity, the type of product in which caffeine is contained, and also on the individual differences among people (sex, age, diet etc.). The main aim of this review was to collect, present, and analyze the available information including the latest discoveries on the impact of caffeine on human health and the functioning of human body systems, taking into account the role of caffeine in individual disease entities. We present both the positive and negative sides of caffeine consumption and the healing properties of this purine alkaloid in diseases such as asthma, Parkinson’s disease, and others, not forgetting about the negative effects of excess caffeine (e.g., in people with hypertension, children, adolescents, and the elderly). In summary, we can conclude, however, that caffeine has a multi-directional influence on various organs of the human body, and because of its anti-oxidative properties, it was, and still is, an interesting topic for research studies including those aimed at developing new therapeutic strategies.

This efficacy trial evaluated the effects of two polyphenolic stilbenes, resveratrol and pterostilbene, mostly found in grapes, on the brush border membrane functionality, morphology and gut microbiome. This study applied the validated Gallus gallus intra-amniotic approach to investigate the effects of stilbene administration versus the controls. Three treatment groups (5% resveratrol; 5% pterostilbene; and synergistic: 4.75% resveratrol and 0.25% pterostilbene) and three controls (18 MΩ H2O; no injection; 5% inulin) were employed. We observed beneficial morphological changes, specifically an increase in the villus length, diameter, depth of crypts and goblet cell diameter in the pterostilbene and synergistic groups, with concomitant increases in the serum iron and zinc concentrations. Further, the alterations in gene expression of the mineral metabolism proteins and pro-inflammatory cytokines indicate a potential improvement in gut health and mineral bioavailability. The cecal microbiota was analyzed using 16S rRNA sequencing. A lower α-diversity was observed in the synergistic group compared with the other treatment groups. However, beneficial compositional and functional alterations in the gut microbiome were detected. Several key microbial metabolic pathways were differentially enriched in the pterostilbene treatment group. These observations demonstrate a significant bacterial–host interaction that contributed to enhancements in intestinal functionality, morphology and physiological status. Our data demonstrate a novel understanding of the nutritional benefits of dietary stilbenes and their effects on intestinal functionality, morphology and gut microbiota in vivo.

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with decreased insulin sensitivity. However, the association between NAFLD and pancreatic β-cell function is still ambiguous. Here, we assessed whether pancreatic β-cell function is associated with NAFLD. Method: The data of NHANES III from 1988 to 1994 were used. NAFLD was diagnosed when subjects had ultrasonographically hepatic steatosis without other liver diseases. Disposition index (DI) was employed to assess pancreatic β-cell function. A total of 6168 participants were included in this study. Results: NAFLD participants had much higher HOMA2-%B (weighted mean, 124.1, standard error, 1.8) than the non-NAFLD participants (weighted mean, 100.7, standard error, 0.9). However, when evaluating the β-cell function in the context of insulin resistance by using DI index, DI levels were much lower in NAFLD subjects (weighted mean, 79.5, standard error, 1.0) compared to non-NAFLD (weighted mean, 95.0, standard error, 0.8). Multivariate logistic regression analyses showed that DI was inversely associated with NAFLD prevalence. The adjusted OR (95% CI) for quartile 1 versus quartile 4 was 1.81 (1.31–2.50) (p &lt, 0.001 for trend). Moreover, DI was also inversely associated with the presence of moderate to severe hepatic steatosis. The multivariable-adjusted ORs across quartiles of DI were 2.47, 1.44, 0.96 and 1.00 for the presence of moderate to severe hepatic steatosis (p &lt, 0.001 for trend). Conclusions: Pancreatic β-cell function might be a new predictor for the presence of NAFLD, and insufficient compensatory β-cell function is associated with NAFLD.

Malnutrition continues to threaten the lives of millions across the world, with children being hardest hit. Although inadequate access to food and infectious disease are the primary causes of childhood malnutrition, the gut microbiota may also contribute. This review considers the evidence on the role of diet in modifying the gut microbiota, and how the microbiota impacts childhood malnutrition. It is widely understood that the gut microbiota of children is influenced by diet, which, in turn, can impact child nutritional status. Additionally, diarrhoea, a major contributor to malnutrition, is induced by pathogenic elements of the gut microbiota. Diarrhoea leads to malabsorption of essential nutrients and reduced energy availability resulting in weight loss, which can lead to malnutrition. Alterations in gut microbiota of severe acute malnourished (SAM) children include increased Proteobacteria and decreased Bacteroides levels. Additionally, the gut microbiota of SAM children exhibits lower relative diversity compared with healthy children. Thus, the data indicate a link between gut microbiota and malnutrition in children, suggesting that treatment of childhood malnutrition should include measures that support a healthy gut microbiota. This could be of particular relevance in sub-Saharan Africa and Asia where prevalence of malnutrition remains a major threat to the lives of millions.

Dietary habits and gut microbiota play an essential role in non-alcoholic fatty liver disease (NAFLD) and related factors such as insulin resistance and de novo lipogenesis. In this study, we investigated the protective effects of Bacteroides uniformis CBA7346, isolated from the gut of healthy Koreans, on mice with high-fat diet (HFD)-induced NAFLD. Administration of B. uniformis CBA7346 reduced body and liver weight gain, serum alanine aminotransferase and aspartate aminotransferase levels, liver steatosis, and liver triglyceride levels in mice on an HFD, the strain also decreased homeostatic model assessment for insulin resistance values, as well as serum cholesterol, triglyceride, lipopolysaccharide, leptin, and adiponectin levels in mice on an HFD. Moreover, B. uniformis CBA7346 controlled fatty liver disease by attenuating steatosis and inflammation and regulating de novo lipogenesis-related proteins in mice on an HFD. Taken together, these findings suggest that B. uniformis CBA7346 ameliorates HFD-induced NAFLD by reducing insulin resistance and regulating de novo lipogenesis in obese mice.

Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.

Pharmacological treatment modalities for non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are scarce, and discoveries are challenged by lack of predictive animal models adequately reflecting severe human disease stages and co-morbidities such as obesity and type 2 diabetes. To mimic human NAFLD/NASH etiology, many preclinical models rely on specific dietary components, though metabolism may differ considerably between species, potentially affecting outcomes and limiting comparability between studies. Consequently, understanding the physiological effects of dietary components is critical for high translational validity. This study investigated the effects of high fat, cholesterol, and carbohydrate sources on NASH development and metabolic outcomes in guinea pigs. Diet groups (n = 8/group) included: low-fat low-starch (LF-LSt), low-fat high-starch (LF-HSt), high-fat (HF) or HF with 4.2%, or 8.4% sugar water supplementation. The results showed that caloric compensation in HF animals supplied with sugar water led to reduced feed intake and a milder NASH phenotype compared to HF. The HF group displayed advanced NASH, weight gain and glucose intolerance compared to LF-LSt animals, but not LF-HSt, indicating an undesirable effect of starch in the control diet. Our findings support the HF guinea pig as a model of advanced NASH and highlights the importance in considering carbohydrate sources in preclinical studies of NAFLD.

Cyclophosphamide (CTX) is widely applied in cancer treatment. However, the outcome is often compromised by lymphopenia, myelosuppression, and gut dysbiosis. Here, we used jujube powder to enhance CTX efficiency through nurturing gut microbiota in order to facilitate favorable metabolisms. It was observed that the oral administration of jujube powder enriched CD8+ T cells in mouse MC38 colon tumor microenvironment and increased the diversity of gut microbiota and the abundance of Bifidobacteriales, which is helpful to the production of butyrate in the cecum content. The application of jujube powder also stimulated the production of white blood cells, especially CD8+ T cells in peripheral and bone marrow, while inhibiting the growth of eosinophils in peripheral blood and the production of IL-7 and GM-CSF in serum. All these are conductive to the significant inhibition of the tumor growth, suggesting the high potential of nurturing gut microbiota with natural products for improving the efficiency of chemotherapy.

Changes in the composition and proportions of the gut microbiota may be associated with numerous diseases, including cognitive impairment. Over the recent years, the growing interest in this relation is observed, but there are still many unknowns, especially in the elderly. To the best of our knowledge, this is the first work that synthesizes and critically evaluates existing evidence on the possible association between human gut microbiota and cognitive function in the elderly. For this purpose, comprehensive literature searches were conducted using the electronic databases PubMed, Google Scholar, and ScienceDirect. The gut microbiota of cognitively healthy and impaired elderly people may differ in the diversity and abundance of individual taxes, but specific taxes cannot be identified. However, some tendencies to changing the Firmicutes/Bacteroidetes ratio can be identified. Currently, clinical trials involving probiotics, prebiotics, and synbiotics supplementation have shown that there are premises for the claim that these factors can improve cognitive functions, however there is no single intervention beneficial to the elderly population. More reliable evidence from large-scale, long-period RCT is needed. Despite proposing several potential mechanisms of the gut microbiota’s influence on the cognitive function impairment, prospective research on this topic is extremely difficult to conduct due to numerous confounding factors that may affect the gut microbiota. Heterogeneity of research outcomes impairs insight into these relations.

Patients suffering from critical illness have host inflammatory responses against injuries, such as infection and trauma, that can lead to tissue damage, organ failure, and death. Modulation of host immune response as well as infection and damage control are detrimental factors in the management of systemic inflammation. The gut is the motor of multiple organ failure following injury, and it is recognized that gut dysfunction is one of the causative factors of disease progression. The gut microbiota has a role in maintaining host immunity, and disruption of the gut microbiota might induce an immunosuppressive condition in critically ill patients. Treatment with probiotics and synbiotics has been reported to attenuate systemic inflammation by maintaining gut microbiota and to reduce postoperative infectious complications and ventilator-associated pneumonia. The administration of prophylactic probiotics/synbiotics could be an important treatment option for preventing infectious complications and modulating immunity. Further basic and clinical research is needed to promote intestinal therapies for critically ill patients.

Cardiovascular diseases (CVDs) can originate from early life. Accumulating evidence suggests that gut microbiota in early life is linked to CVDs in later life. Gut microbiota-targeted therapy has gained significant importance in recent decades for its health-promoting role in the prevention (rather than just treatment) of CVDs. Thus far, available gut microbiota-based treatment modalities used as reprogramming interventions include probiotics, prebiotics, and postbiotics. The purpose of this review is, first, to highlight current studies that link dysbiotic gut microbiota to the developmental origins of CVD. This is followed by a summary of the connections between the gut microbiota and CVD behind cardiovascular programming, such as short chain fatty acids (SCFAs) and their receptors, trimethylamine-N-oxide (TMAO), uremic toxins, and aryl hydrocarbon receptor (AhR), and the renin-angiotensin system (RAS). This review also presents an overview of how gut microbiota-targeted reprogramming interventions can prevent the developmental origins of CVD from animal studies. Overall, this review reveals that recent advances in gut microbiota-targeted therapy might provide the answers to reduce the global burden of CVDs. Still, additional studies will be needed to put research findings into practice.

Vitamin K (VK) is a ligand of the pregnane X receptor (PXR), which plays a critical role in the detoxification of xenobiotics and metabolism of bile acids. VK1 may reduce the risk of death in patients with chronic liver failure. VK deficiency is associated with intrahepatic cholestasis, and is already being used as a drug for cholestasis-induced liver fibrosis in China. In Japan, to treat osteoporosis in patients with primary biliary cholangitis, VK2 formulations are prescribed, along with vitamin D3. Animal studies have revealed that after bile duct ligation-induced cholestasis, PXR knockout mice manifested more hepatic damage than wild-type mice. Ligand-mediated activation of PXR improves biochemical parameters. Rifampicin is a well-known human PXR ligand that has been used to treat intractable pruritus in severe cholestasis. In addition to its anti-cholestatic properties, PXR has anti-fibrotic and anti-inflammatory effects. However, because of the scarcity of animal studies, the mechanism of the effect of VK on cholestasis-related liver disease has not yet been revealed. Moreover, the application of VK in cholestasis-related diseases is controversial. Considering this background, the present review focuses on the effect of VK in cholestasis-related diseases, emphasizing its function as a modulator of PXR.

The human gut microbiota are the microorganisms (generally bacteria and archaea) that live in the digestive tracts of humans. Due to their numerous functions, the gut microbiota can be considered a virtual organ of the body, playing a pivotal role in health maintenance. Dietary habits contribute to gut microbiota composition, and evidence from observational and intervention studies suggest that vegan diets may promote health, potentially through affecting the diverse ecosystem of beneficial bacteria in the gut. A systematic literature search was conducted on PubMed and Scopus to identify studies investigating the microbiota composition in vegans. Vegans are defined as people excluding food products that are derived from animals from their diet. Nine observational studies were identified. The main outcome of the systematic review was an increase in Bacteroidetes on the phylum level and a higher abundance of Prevotella on the genus level. In conclusion, the present systematic literature review highlighted some benefits of a vegan diet but also demonstrated the complexity of evaluating results from gut microbiota research. The available evidence only consisted of cross-sectional studies, therefore suggesting the need for well-designed randomised controlled trials. Furthermore, the quality assessment of the studies included in the review suggested a lack of standardised and validated methods for participant selection as well as for faecal sampling and faecal analysis.

Gut microbiota dysbiosis is a common feature in colorectal cancer (CRC) and inflammatory bowel diseases (IBD). Adoption of the Mediterranean diet (MD) has been proposed as a therapeutic approach for the prevention of multiple diseases, and one of its mechanisms of action is the modulation of the microbiota. We aimed to determine whether MD can be used as a preventive measure against cancer and inflammation-related diseases of the gut, based on its capacity to modulate the local microbiota. A joint meta-analysis of publicly available 16S data derived from subjects following MD or other diets and from patients with CRC, IBD, or other gut-related diseases was conducted. We observed that the microbiota associated with MD was enriched in bacteria that promote an anti-inflammatory environment but low in taxa with pro-inflammatory properties capable of altering intestinal barrier functions. We found an opposite trend in patients with intestinal diseases, including cancer. Some of these differences were maintained even when MD was compared to healthy controls without a defined diet. Our findings highlight the unique effects of MD on the gut microbiota and suggest that integrating MD principles into a person’s lifestyle may serve as a preventive method against cancer and other gut-related diseases.