Search Results (355)

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management. Full article

The enteroendocrine system of the gastrointestinal (GI) tract is the largest endocrine organ in the human body, playing a central role in the regulation of hunger, satiety, digestion, and energy homeostasis. Numerous factors—including dietary components, physical activity, and the gut microbiota—affect the secretion of GI hormones. This study aims to analyze how these factors modulate enteroendocrine function and influence systemic metabolic regulation. This review synthesizes the current scientific literature on the physiology and distribution of enteroendocrine cells and mechanisms of hormone secretion in response to macronutrients, physical activity, and microbial metabolites. Special attention is given to the interactions between gut-derived signals and central nervous system pathways involved in appetite control. Different GI hormones are secreted in specific regions of the digestive tract in response to meal composition and timing. Macronutrients, particularly during absorption, stimulate hormone release, while physical activity influences hormone concentrations, decreasing ghrelin and increasing GLP-1, PYY, and leptin levels. The gut microbiota, through fermentation and metabolite production (e.g., SCFAs and bile acids), modulates enteroendocrine activity. Species such as Akkermansia muciniphila are associated with improved gut barrier integrity and enhanced GLP-1 secretion. These combined effects contribute to appetite regulation and energy balance. Diet composition, physical activity, and gut microbiota are key modulators of gastrointestinal hormone secretion. Their interplay significantly affects appetite regulation and metabolic health. A better understanding of these relationships may support the development of personalized strategies for managing obesity and related disorders. Full article

The recent identification of early-onset mutational signatures with geographic variations by Diaz-Gay et al. is a significant finding, since early-onset colorectal cancer has emerged as an alarming public health challenge in the past two decades, and the pathomechanism remains unclear. Environmental risk factors, including lifestyle and diet, are highly suspected. The identification of colibactin from Escherichia coli as a potential pathogenic source is a major step forward in addressing this public health challenge. Therefore, the following opinion manuscript aims to outline the likely onset of the pathomechanism and the critical role of acquired Piezo2 channelopathy in early-onset colorectal cancer, which skews proton availability and proton motive force regulation toward E. coli within the microbiota–host symbiotic relationship. In addition, the colibactin produced by the pks island of E. coli induces host DNA damage, which likely interacts at the level of Wnt signaling with Piezo2 channelopathy-induced pathological remodeling. This transcriptional dysregulation eventually leads to tumorigenesis of colorectal cancer. Mechanotransduction converts external physical cues to inner chemical and biological ones. Correspondingly, the proposed quantum mechanical free-energy-stimulated ultrafast proton-coupled tunneling, initiated by Piezo2, seems to be the principal and essential underlying novel oscillatory signaling that could be lost in colorectal cancer onset. Hence, Piezo2 channelopathy not only contributes to cancer initiation and impaired circadian regulation, including the proposed hippocampal ultradian clock, but also to proliferation and metastasis. Full article

Colorectal cancer (CRC) is associated with factors such as an unhealthy diet, physical inactivity, obesity, diabetes, and chronic inflammatory conditions like inflammatory bowel disease (IBD), as well as TP53 mutations, which are observed in a broad spectrum of CRC. Additionally, alteration in the composition of the gut microbiome community and metabolism plays a significant role in the development of colorectal cancer and its therapeutic effects. It is well known that treatment with sodium butyrate (NaB), an intestinal microbial metabolite, can induce apoptosis by activating histone deacetylase (HDAC) in cancer cells. Therefore, this study examined the relationship between NaB-induced apoptosis and p53 protein level in colorectal cancer cells. Treatment with NaB triggered cell death in the HCT116 cell line. Furthermore, a notable elevation in p53 protein level was detected following treatment with a high concentration of NaB, compared to both the control group and the low concentration NaB. Furthermore, apoptotic cell death was diminished in a p53-deficient cell line (HCT 116 p53^−/−) and p53 protein expression was more stabilized. Although p53 mRNA expression was not affected, acetylation of p53 protein was clearly observed by high concentration NaB treatment. To demonstrate the relationship between p53 acetylation and cell death, HT29 cells were treated with a high concentration of NaB. In HT29 cells with a mutation in the p53 gene, increased cell viability, overproduction p53 protein, and hyperacetylation of p53 were observed compared to the control. The results of this study suggest that p53 protein expression plays an important role in the effectiveness of therapy utilizing gut microbiota metabolites. Full article

The S100B protein, known for its role in the central and enteric nervous systems, has recently been identified in dietary sources such as milk, dairy products, fruits, and vegetables. Given its potential interaction with the gut microbiota, this study explores the relationship between dietary intake of S100B and microbiota biodiversity across different diets. A comprehensive study was conducted, estimating S100B concentrations in 13 dietary patterns recommended in different countries. This is the first study to provide a comparative estimation of S100B exposure from the diet and to explore its potential ecological and epidemiological relevance. The association between S100B levels and microbiota biodiversity was statistically analyzed, showing a direct correlation. Microbial diversity was assessed using the Shannon index, based on data extracted from studies reporting microbiota composition across dietary patterns. Additionally, the relative risk of Crohn’s disease was assessed in different populations to examine potential links between dietary patterns, S100B, and chronic disease prevention. A moderate positive correlation (R² = 0.537) was found between S100B concentration and Shannon index, suggesting that diets higher in S100B (e.g., Mediterranean diet) were associated with higher microbial alpha-diversity. Furthermore, Western-style diets, with the lowest S100B levels, exhibited a higher relative risk for Crohn’s disease (R² = 0.780). These findings highlight the potential role of dietary S100B content in modulating gut microbiota diversity and reducing chronic disease risk. Full article

The gut microbiota plays an important role in maintaining the body’s homeostasis, and its disruption has been linked to the pathogenesis of coronary atherosclerosis and cognitive decline. This review attempted to assess whether the composition of the gut microbiota differs significantly according to the severity of coronary atherosclerosis and whether the presence of specific cytokines and inflammatory markers in the microbiota of patients with atherosclerosis may correlate with cognitive impairment. In addition, it considered whether increased dietary fiber intake may contribute to lower levels of inflammatory markers compared to a low-fiber diet. This review included publications from 2015 to 2024, searched in the PubMed and Scopus databases. Only studies meeting the quality criteria were included. The pooled data indicate that intestinal dysbiosis can lead to increased intestinal barrier permeability and lipopolysaccharide (LPS) translocation, which promotes chronic inflammation. This process plays an important role in both atherosclerosis and neurodegeneration. In addition, some studies indicate a beneficial effect of dietary fiber in reducing inflammatory markers. The conclusions of this review highlight the need for further, well-designed studies to identify the causal relationship between the microbiota, its metabolites, atherosclerosis, and cognitive deficits, which may provide the basis for new therapeutic strategies. Full article

The gut microbiota, dominated by bacteria from the Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla, plays an essential role in fermenting indigestible carbohydrates, regulating metabolism, synthesizing vitamins, and maintaining immune functions and intestinal barrier integrity. Dysbiosis is associated with obesity development. Shifts in the ratio of Firmicutes to Bacteroidetes, particularly an increase in Firmicutes, may promote enhanced energy storage, appetite dysregulation, and increased inflammatory processes linked to insulin resistance and other metabolic disorders. The purpose of this literature review is to summarize the current state of knowledge on the relationship between the development and treatment of obesity and overweight and the gut microbiota. Current evidence suggests that probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) can influence gut microbiota composition and metabolic parameters, including body weight and BMI. The most promising effects are observed with probiotic supplementation, particularly when combined with prebiotics, although efficacy depends on strain type, dose, and duration. Despite encouraging preclinical findings, FMT has shown limited and inconsistent results in human studies. Diet and physical activity are key modulators of the gut microbiota. Fiber, plant proteins, and omega-3 fatty acids support beneficial bacteria, while diets low in fiber and high in saturated fats promote dysbiosis. Aerobic exercise increases microbial diversity and supports growth of favorable bacterial strains. While microbiota changes do not always lead to immediate weight loss, modulating gut microbiota represents an important aspect of obesity prevention and treatment strategies. Further research is necessary to better understand the mechanisms and therapeutic potential of these interventions. Full article

Neuroinflammation is a hallmark of many neuropsychiatric disorders (NPD), which are among the leading causes of disability worldwide. Emerging evidence highlights the significant role of the gut microbiota (GM)–immune system–brain axis in neuroinflammation and the pathogenesis of NPD, primarily through epigenetic mechanisms. Gut microbes and their metabolites influence immune cell activity and brain function, thereby contributing to neuroinflammation and the development and progression of NPD. The enteric nervous system, the autonomic nervous system, neuroendocrine signaling, and the immune system all participate in bidirectional communication between the gut and the brain. Importantly, the interaction of each of these systems with the GM influences epigenetic pathways. Here, we first explore the intricate relationship among intestinal microbes, microbial metabolites, and immune cell activity, with a focus on epigenetic mechanisms involved in NPD pathogenesis. Next, we provide background information on the association between inflammation and epigenetic aberrations in the context of NPD. Additionally, we review emerging therapeutic strategies—such as prebiotics, probiotics, methyl-rich diets, ketogenic diet, and medications—that may modulate the GM–immune system–brain axis via epigenetic regulation for the prevention or treatment of NPD. Finally, we discuss the challenges and future directions in investigating the critical role of this axis in mental health. Full article

HIV-associated neurocognitive disorders (HANDs) refer to a range of cognitive deficits that afflict people living with the Human Immunodeficiency Virus (HIV). The fundamental processes of HAND include persistent inflammation, immunological activation, and direct viral impact on the central nervous system. Emerging research shows that nutritional status, especially food consumption and body weight, is critical in determining the course and severity of HAND. Malnutrition exacerbates neurocognitive impairment by increasing inflammation and oxidative stress, while obesity may contribute to HAND through the promotion of metabolic disruption, gut microbiota alterations, and systemic inflammation. Additionally, the introduction of antiretroviral treatment (ART) has substantially enhanced the prognosis of people living with HIV by lowering viral load and improving immune function. However, depending on the regimen, ART can cause changes in body weight, which may influence the progression of HAND. This emphasizes the intricate interplay between HIV, nutrition, body weight, and neurocognitive health. As a result, various dietary approaches are currently being investigated to improve the quality of life of individuals with HIV and possibly help prevent neurocognitive decline in this population. This review aims to elucidate the relationship between nutrition and neurocognitive function in individuals living with HIV, shedding light on aspects of HANDs related to diet, body weight fluctuations, and metabolic syndrome. It explores the shift from current pharmacological treatments to innovative non-pharmacological interventions, including specific dietary strategies, to support overall health and cognitive well being in HIV-positive people. Full article

Gut microbiota “enterotypes” are strongly associated with diet and host health. For grazing animals, plant species richness and nutrient content of vegetation may alter the food supply and diet composition of animals. Understanding this relationship is critical to clarify the adaption of gut microbiota to changes in vegetation quantity and quality in grassland ecosystems. Here, we studied the relationship between dietary and gut microbiota composition of sheep (lambs) over a growing season in a grassland ecosystem in northern China. Variation in vegetation composition among grazing intensities was greatest in September: and sheep preferred forbs and Rosaceae throughout the grazing period in all grazing treatments, yet their preference for Fabaceae was reduced in HG treatments in September. Grazing intensity and seasonal variations in food resource availability influenced dietary patterns, which in turn affected gut bacterial community composition. Enterotype 1, dominated by Christensenellaceae_R_7_group and Clostridia_UCG_014_unclassified, predominated during the warm season (July) for both LG and HG treatments. In contrast, Enterotype 2, dominated by Escherichia_Shigella, prevailed during the cool season (September) in HG. Diversity of Enterotype 1 exceeded (p < 0.001) that of Enterotype 2. For MG, Enterotype 1 and Enterotype 2 were evenly distributed over the grazing period. Our results highlight the importance of regulating grazing intensity to maintain the balance and health of gut microbiota according to temporal changes in plant nutrients and aboveground biomass of grassland ecosystems. Full article

Chronic kidney disease (CKD) has a high prevalence worldwide, with an increasing incidence. One of the mechanisms of CKD progression involves a disordered inter-organ relationship between the kidneys and the intestine, known as the kidney-gut axis. In CKD, two pathological gut conditions—disturbed gut microbiota composition called uremic dysbiosis and leaky gut—contribute to the progression of CKD. Dysbiosis is associated with the increased production of gut-derived uremic toxins, leaky gut, and chronic systemic inflammation, leading to worsening uremia, which in turn aggravates the gut condition. This vicious cycle should be a target of the therapeutic strategy against CKD. The modulation of uremic dysbiosis, including prebiotics, probiotics, and synbiotics, has been a typical treatment approach, although clinical evidence for their efficacy has been insufficient. Some non-antibiotic drugs have an impact on human gut bacteria that are believed to play a role in their clinical efficacy on kidney function. Nutrition therapies, including a low-protein diet, dietary fiber, a Mediterranean diet, and whole grains, positively influence gut microbiota composition and have been linked to a decreased risk of CKD. Novel strategies are currently being explored, involving the use of postbiotics, microbiome sequencing techniques, and fecal microbiota transplantation, although clinical application remains to be tested. Human trials investigating the above-mentioned interventions remain inconclusive due to several limitations, including dietary variability and genetic factors. Future research should focus on the development of more effective probiotics, prebiotics, and microbial metabolism-modifying drugs, not only for CKD but for other systemic diseases as well. Full article

Background: Food allergy (FA) is associated with dietary habits, antibiotic use, living environment, and delivery method. Pregnancy and lactation represent critical periods for neonatal immune system development. Methods: This study investigated the relationship between maternal dietary habits and FA risk in offspring. Pregnant C57BL/6J mice (8-week-old males and females) were fed either a high-fat diet (HFD) or HFD supplemented with fermented apple juice (FAJ) during pregnancy and lactation. Offspring were nursed by their respective dams until weaning at 21 days postpartum, followed by ovalbumin (OVA) sensitization. Lipid profiles, acylcarnitines, immunological, and histopathological analyses were performed. Gut microbiota composition and serum markers were also assessed. Results: The findings indicated that maternal HFD had a negative impact on OVA-sensitized offspring mice. Early-life FAJ intervention modulated gut microbiota alterations and alleviated maternal HFD-worsened allergic symptoms through Th1/Th2 and Th17/Treg immunity balance and intestinal barrier repair. Maternal serum triglyceride and total cholesterol levels, along with gut microbiota profiles, significantly influenced offspring gut microbiota composition. Moreover, reduced short-chain and medium-chain acylcarnitines in offspring may be associated with increased allergy risk. Conclusions: Maternal HFD during pregnancy and lactation disrupted gut microbiota balance and exacerbated offspring FA susceptibility. These findings provide a scientific foundation for developing early-life FA prevention strategies. Full article

Precision nutrition-targeted gut microbiota (GM) may have therapeutic potential not only for age-related diseases but also for slowing the aging process and promoting longer healthspan. Recent studies have shown that restoring a healthy symbiosis of GM by counteracting dysbiosis (DYS) through precise nutritional intervention is becoming a major target for extending healthspan. Microbiota-accessible borate (MAB) complexes, such as boron (B)–pectins (rhamnogalacturonan–borate) and borate–phenolic esters (diester chlorogenoborate), have a significant impact on healthy host–microbiota symbiosis (HMS). The mechanism of action of MABs involves the biosynthesis of the autoinducer-2–borate (AI-2B) signaling molecule, B fortification of the mucus gel layer by the MABs diet, inhibition of pathogenic microbes, and reversal of GM DYS, strengthening the gut barrier structure, enhancing immunity, and promoting overall host health. In fact, the lack of MAB complexes in the human diet causes reduced levels of AI-2B in GM, inhibiting the Firmicutes phylum (the main butyrate-producing bacteria), with important effects on healthy HMS. It can now be argued that there is a relationship between MAB-rich intake, healthy HMS, host metabolic health, and longevity. This could influence the deployment of natural prebiotic B-based nutraceuticals targeting the colon in the future. Our review is based on the discovery that MAB diet is absolutely necessary for healthy HMS in humans, by reversing DYS and restoring eubiosis for longer healthspan. Full article

Exercise and diet modulate the gut microbiota, which is involved in the regulation of orthopaedic diseases and synthesises a wide range of metabolites that modulate cellular function and play an important role in bone development, remodelling and disease. G protein-coupled receptors (GPCRs), the largest family of transmembrane receptors in the human body, interact with gut microbial metabolites to regulate relevant pathological processes. This paper provides a review of different dietary and exercise effects on the pathogenic gut microbiota and their metabolites associated with GPCRs in orthopaedic diseases. RESULTS: Generally, metabolites produced by gut microbiota contribute to the maintenance of bone health by activating the corresponding GPCRs, which are involved in bone metabolism, regulation of immune response, and maintenance of gut flora homeostasis. Exercise and diet can influence gut microbiota, and an imbalance in gut microbiota homeostasis can trigger a series of adverse immune and metabolic responses by affecting GPCR function, ultimately leading to the onset and progression of various orthopaedic diseases. Understanding these relationships is crucial for elucidating the pathogenesis of orthopaedic diseases and developing personalised probiotic-based therapeutic strategies. In the future, we should further explore how to prevent and treat orthopaedic diseases through GPCR-based modulation of gut microbes and their interactions. The development of substances that precisely modulate gut microbes through different exercises and diets will provide more effective interventions to improve bone health in patients. Full article

The existing body of evidence has highlighted gut microbiota as a versatile regulator of body wellness affecting not only multiple physiological metabolisms but also the function of remote organs. Emerging studies revealed a reciprocal relationship between physical exercise and intestinal microbiota, suggesting that physical exercise could enhance gut health, including regulating intestinal barrier integrity, increasing microbial diversity, and promoting beneficial microbial metabolism. Furthermore, the beneficial outcomes of exercise on the intestine may also promote brain health through the gut–brain axis. Diet is an important factor in boosting exercise performance and also greatly impacts the structure of gut microbiota. Abundant research has reported that diet alongside exercise could exert beneficial effects on metabolism, immune regulation, and the neuropsychiatric system. In this paper, we used a narrative review, primarily searching PubMed, Web of Science, and Elsevier, to review the existing research on how moderate-intensity exercise promotes gut health, and we introduced the effects of exercise on the nervous system through the gut–brain axis. We also proposed dietary strategies targeting the regulation of gut microbiota to provide guidelines for boosting brain health. This review highlights that moderate exercise and a healthy diet promote gut and brain health. Full article