Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

Obesity is a prevalent chronic condition worldwide, posing a significant risk to public health. Polysaccharides derived from Platycodonis Radix (PR) have been identified as the primary bioactive compounds in combating obesity, although the underlying molecular mechanisms remain inadequately understood.

The purpose of the research is to analyze the potential anti-obesity influnces within PR polysaccharides (PG: PG1 and PG2) by analyzing their impact on gut microbiota (GM) composition, SCFA and BA metabolism, and the regulation of associated gene and protein expression.

In this research, 7-week-old male C57BL/6 mice were assigned to a HFD or a control chow diet for 90 days to evaluate the therapeutic effects of PG intervention. Metagenomic analysis was performed to assess GM alterations, while GC-MS and LC-MS were used to quantify SCFA and BA concentrations in cecal contents, respectively. Furthermore, the effects of PG on SCFA- and BA-associated metabolic pathways were examined through qRT-PCR and WB.

PG1 demonstrated superior efficacy compared to PG2 in reducing HFD-induced obesity and associated metabolic disturbances. High-dose PG1 treatment effectively inhibited weight gain, dyslipidemia, inflammation, liver damage, and fat deposition caused by the HFD. Additionally, PG1 treatment primarily promoted the abundance of SCFA-producing bacteria, enhanced the expression of GPR41 and GPR43 genes, significantly elevated levels of GLP-1 and PYY, and improved circulating leptin and adiponectin levels. The intervention with PG1 notably enhanced the relative abundances of bacteria involved in the production of secondary BAs, such as Lachnospiraceae_NK4A136 and Eubacterium coprostanoligenes. This augmentation facilitated the transformation of primary BAs into secondary forms, diminished the relative expression of intestinal FXR and FGF15, and reduced FGFR4 levels. Consequently, this led to an upregulation of hepatic CYP7A1, accelerating liver cholesterol metabolism and the synthesis of new BAs.

Supplementation with PG1 protects mice from obesity induced by an HFD. The observed protective effects of PG1 appear to be primarily mediated through the activation of the GM-SCFA-GPR pathway and the inhibition of the GM-BA-FXR-FGF15 signaling pathway.

Fermented dairy products are known for their efficiency in delivering and protecting probiotic microorganisms. However, there is a growing demand for diversification of the market with plant-based products. The aim of this study was to develop an oat beverage enriched with inulin and fermented with Lacticaseibacillus rhamnosus LR B and evaluate its synbiotic effects in vitro. For this purpose, the validated dynamic colon model (the TNO Intestinal Model TIM-2) was used with focus on the composition of the gut microbiota and its production of metabolites to evaluate the functionality. The fermentation kinetics, sugars, organic acids and inulin dosage in the fermented oat beverage were also evaluated. The acidification rate was 16.91 10-3 pH units.min-1, reaching the final pH of 4.5 in 2.38 ± 0.05 h. Dosages of sucrose, glucose and lactic acid were 23.35 ± 0.45 g.L-1, 21.37 ± 0.77 g.L-1, 0.94 ± 0.05 g.L-1, respectively. After simulated in vitro digestion, the inulin concentration was partially preserved with 20.11 ± 0.21 maltose equivalent (μg.mL-1). The fermented and pre-digested oat beverage (with 7.71 ± 0.44 log CFU.mL-1) was fed into TIM-2, which was previously inoculated with feces from healthy adults. The analysis identified nine bacterial taxa that were significantly modulated compared to the standard ileal effluent medium (SIEM) control. An increase in relative abundance of Lactobacillus and Catenibacterium, and reduction in Citrobacter, Escherichia-Shigella, and Klebsiella was observed. In addition, the cumulative means of short-chain fatty acids (SCFAs) increased, especially for acetate and butyrate. These findings suggest that the developed oat beverage can positively influence the gut microbiota and its activity, highlighting possible health benefits.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by hyperglycemia and insulin resistance. Plantain shell powder (PHP) serves as a high-quality source of dietary fiber, widely utilized in food additives and pharmaceutical applications. In this study, we investigated the hypoglycemic activity and underlying mechanisms of PHP by examining its effects on intestinal microbiota and metabolism in T2DM mice induced by a high-fat diet and streptozotocin (STZ). Our findings indicate that PHP significantly enhances blood glucose homeostasis and insulin sensitivity, reduces organ damage, and regulates blood lipid levels as well as short-chain fatty acid concentrations; notably, higher doses of PHP yielded optimal results. In addition, PHP can regulate the ratio of Bacteroidota to Firmicutes and increase the relative abundance of beneficial bacteria such as Bacteroidales, Muribaculaceae, and Parabacteroides. Furthermore, PHP enhances the enrichment of key metabolic pathways, including α-linolenic acid metabolism, monobactam biosynthesis, and PPAR signaling pathways, thereby promoting the production of beneficial metabolites. Complex interactions exist among these beneficial bacteria and metabolic pathways that are associated with improved metabolic function, regulation of glucose homeostasis, enhancement of insulin sensitivity, and reduction of inflammation. Our study demonstrates that PHP can ameliorate T2DM by reversing alterations in gut microbiota and metabolic profiles caused by T2DM while promoting the regulation of beneficial microbial populations.

Colonic permeability is a major consequence of dysbiosis and diseases affecting the colon, further contributing to inflammation and extraintestinal diseases. Recent advances have shed light on the association between colonocyte energy utilization and the mechanisms that support epithelial function and homeostasis. One unifying theme is the induction of colonocyte hypoxia, driven by the aerobic oxidation of microbial-derived butyrate, as a critical factor promoting multiple cellular processes that support intestinal barrier function, mucus secretion, and the maintenance of synergistic luminal microbes. Particular attention will be focused on experimental evidence supporting beta-oxidation via activation of peroxisome proliferators-activated receptor-γ (PPAR) and upregulation and activation of processes that promote barrier function by hypoxia-inducible factor (HIF) signaling. Growing evidence suggests that colonocyte energy utilization is tightly regulated and switches between beta-oxidation of butyrate and anaerobic glycolysis, the latter being associated with several disease states. As most of the primary literature associated with colonocyte energy utilization has focused on adult models, evidence supporting butyrate oxidation in the neonatal gut is lacking. Thus, this review details the current state of knowledge linking colonocyte substrate utilization to mechanisms supporting gut health, but also highlights the counterindications of colonic butyrate availability and utilization in developmental periods.

In recent years, the gut microbiota has been increasingly recognized for its influence on various central nervous system diseases mediated by microglia, yet the underlying mechanisms remain unclear. As key metabolites of the gut microbiota, short-chain fatty acids (SCFAs) have emerged as a focal point in understanding microglia-related interactions. In this review, we further refine the connection between the gut microbiota and microglia by introducing the concept of the "SCFAs-microglia" pathway. We summarize current knowledge on this pathway, recent discoveries regarding its role in neurological diseases, and potential pharmacological strategies targeting it. Finally, we outlined the current challenges and limitations in this field of research. We hope this review provides new insights into the role of the gut microbiota in neuroimmune regulation.

Oat beta-glucans (OBGs) lower postprandial blood glucose by increasing gastrointestinal viscosity, delaying gastric emptying, and slowing glucose absorption. While the European Food Safety Authority (EFSA) recommends a minimum intake of 4 g of OBGs per 30 g of available carbohydrates (avCHO) for a significant reduction in glycaemic response, this poses formulation challenges. This study investigated the effects of a commercially available OBG ingredient on postprandial glycemia and appetite sensations immediately after ingestion and following a standardized lunch 3.5 hours later, also exploring whether doses below 4 g of OBGs per 30 g of avCHO could be effective. Nineteen healthy subjects consumed test drinks containing 0 g (Ref), 2 g (BG2), 3 g (BG3), or 4 g (BG4) of OBGs, each providing 30 g of avCHO, in a crossover study. BG2 and BG4 reduced the incremental glucose peak (iPeak) compared to Ref (P < 0.05), with BG3 showing a trend (P = 0.09). BG4 reduced an early glucose incremental area under the curve (iAUC 0-60 min) and improved the post-lunch glycaemic response compared to Ref (P < 0.05). Insulin iPeaks and iAUC (0-120 min) were lower for BG3 and BG4 (P < 0.05). BG4 enhanced satiety and reduced hunger throughout the experimental period (P < 0.05). Doses below 4 g of OBGs per 30 g of avCHO improved postprandial glycemia and appetite, and OBG intake at breakfast enhanced post-lunch glycaemic regulation, suggesting that a lower threshold may be effective in blood glucose management and appetite control.

Obesity is a major global health issue, and novel dietary approaches are needed for prevention and management. This study investigates the effect of insoluble konjac glucomannan (iKGM) derived from edible konnyaku, a traditional Japanese food, on weight gain suppression in mice. Mice treated with iKGM showed increased fecal volume, reduced food intake, and suppressed weight gain (Day 21; p < 0.01). This weight-suppression effect was prebiotic rather than physical properties of iKGM, as antibiotic treatment abolished the weight-suppressing effect despite increased fecal volume. iKGM treatment altered the gut microbiota, notably increasing Akkermansia muciniphila (Day 21; p < 0.01), a bacterium associated with weight loss, along with elevated levels of short-chain fatty acids (SCFAs) such as butyrate and propionate (Day 21; p < 0.01). Furthermore, iKGM-induced weight suppression was linked to elevated leptin levels (Day 21; p < 0.01), an appetite suppressant induced by SCFAs. These results suggest that iKGM modulates gut microbiota, increases A. muciniphila, induces leptin production, and reduces food intake, inhibiting weight gain. This study indicates that iKGM may represent a promising approach for obesity prevention through gut microbiota modulation. Future research should investigate the mechanisms of iKGM's effects on microbiota and explore its long-term safety and efficacy in clinical trials.

Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) (P < 0.05). Interestingly, gender-specific analysis showed that per standard deviation (SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio (95% confidence interval) of 1.16 (1.05-1.29) for total SCFAs and 1.18 (1.07-1.31) for propionate, respectively (P < 0.05, false discovery rate (FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate (P interaction < 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant (P < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.

Public concern over drug resistance has led to governmental regulations banning the use of antibiotics as growth promoters, stimulating interest in developing complementary strategies to maintain animal production, mitigate infections, and enhance muscle characteristics and quality parameters, especially in meat-producing animals. Probiotics are recognized as a potential strategy for improving growth, primarily by promoting intestinal homeostasis. These microorganisms are suggested to modulate gut microbiota, preserving their ecosystem and influencing secondary metabolite production, which can directly or indirectly regulate skeletal muscle metabolism by influencing the expression of key muscle-related genes and the activity of various signaling factors. Several studies have documented the potential benefits of various strains of Bacillus, Enterococcus, and members of the Lactobacillaceae family on muscle characteristics. These studies have shown that probiotics not only modulated myogenic factors but also influenced proteins and enzymes involved in signaling pathways related to carbon metabolism, inflammatory response, mitochondrial dynamics, and antioxidant activity. These effects have been associated with improvements in meat quality parameters and enhanced growth performance. This manuscript seeks to present a brief overview of the impact of probiotic supplementation on muscle health and the quality of meat in broiler chickens.

With its increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major global public health concern over the past few decades. Growing evidence has proposed the microbiota-derived metabolites short-chain fatty acids (SCFAs) as a potential factor in the pathophysiology of MASLD and related metabolic conditions, such as obesity and type 2 diabetes mellitus (T2DM). By influencing key pathways involved in energy homeostasis, insulin sensitivity, and inflammation, SCFAs play an important role in gut microbiota composition, intestinal barrier function, immune modulation, and direct metabolic signaling. Furthermore, recent animal and human studies on therapeutic strategies targeting SCFAs demonstrate their potential for treating these metabolic disorders.

Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.

Evidence is accumulating that short-chain fatty acids (SCFAs) produced by the gut microbiota play pivotal roles in host metabolism. They contribute to the metabolic regulation and energy homeostasis of the host not only by preserving intestinal health and serving as energy substrates but also by entering the systemic circulation as signaling molecules, affecting the gut-brain axis and neuroendocrine-immune network. This review critically summarizes the current knowledge regarding the effects of SCFAs in the fine-tuning of the pathogenesis of type 2 diabetes mellitus (T2DM) and insulin resistance, with an emphasis on the complex relationships among diet, microbiota-derived metabolites, T2DM inflammation, glucose metabolism, and the underlying mechanisms involved. We hold an optimistic view that elucidating how diet can influence gut bacterial composition and activity, SCFA production, and metabolic functions in the host will advance our understanding of the mutual interactions of the intestinal microbiota with other metabolically active organs, and may pave the way for harnessing these pathways to develop novel personalized therapeutics for glucometabolic disorders.

The gut microbiome, comprising bacteria, viruses, fungi, and bacteriophages, is one of the largest microbial ecosystems in the human body and plays a crucial role in various physiological processes. This review explores the interaction between the gut microbiome and enteroendocrine cells (EECs), specialized hormone-secreting cells within the intestinal epithelium. EECs, which constitute less than 1% of intestinal epithelial cells, are key regulators of gut-brain communication, energy metabolism, gut motility, and satiety. Recent evidence shows that gut microbiota directly influence EEC function, maturation, and hormone secretion. For instance, commensal bacteria regulate the production of hormones like glucagon-like peptide 1 and peptide YY by modulating gene expression and vesicle cycling in EE cells. Additionally, metabolites such as short-chain fatty acids, derived from microbial fermentation, play a central role in regulating EEC signaling pathways that affect metabolism, gut motility, and immune responses. Furthermore, the interplay between gut microbiota, EECs, and metabolic diseases, such as obesity and diabetes, is examined, emphasizing the microbiome's dual role in promoting health and contributing to disease states. This intricate relationship between the gut microbiome and EECs offers new insights into potential therapeutic strategies for metabolic and gut disorders.

Dietary fiber can suppress excess adipose tissue and weight gain in rodents and humans when fed high fat diets. The gut microbiome is thought to have a key role, although exactly how remains unclear. In a tightly controlled murine study, we explored how different types of dietary fiber and doses affect the gut microbiota and gut epithelial gene expression. We show that 10% pectin and 10% FOS suppress high fat diet (HFD)-induced weight gain, effects not seen at 2% doses. Furthermore, 2 and 10% mixtures of dietary fiber were also without effect. Each fiber treatment stimulated a distinct gut microbiota profile at the family and operational taxonomic unit (OTU) level. Mechanistically it is likely that the single 10% fiber dose shifted selected bacteria above some threshold abundance, required to suppress body weight, which was not achieved by the 10% Mix, composed of 4 fibers each at 2.5%. Plasma levels of the gut hormone PYY were elevated by 10% pectin and FOS, but not 10% mixed fibers, and similarly RNA seq revealed some distinct effects of the 10% single fibers on gut epithelial gene expression. These data show how the ability of dietary fiber to suppress HFD-induced weight gain is dependent upon both fiber type and dose. It also shows that the microbial response to dietary fiber is distinct and that there is not a single microbial response associated with the inhibition of adiposity and weight gain. PYY seems key to the latter response, although the role of other factors such as Reg3γ and CCK needs to be explored.

This study aimed to investigate the changes in fecal short-chain fatty acids (SCFAs) content in UCP1 knock-in pigs (KI pigs) and their effect on adipogenesis. Fecal samples from five 6-month-old wild-type (WT) and KI pigs were collected for targeted metabolomics and 16s rRNA sequencing analyses to identify differences in SCFAs and gut microbiota that may contribute to regulating fat deposition in pigs. The metabolome of pig fecal samples targeted for an analysis of SCFAs identified seven SCFAs, with caproic acid (except isovaleric acid) being the significantly different one. The results of the fecal 16s rRNA analysis demonstrated a notable reduction in the abundance of Streptococcus spp. in the KI pigs in comparison to the WT pigs, with a statistically significant difference. Correlation analyses demonstrated a statistically significant positive correlation between the abundance of Streptococcus spp. and SCFAs, as well as pig body weight and fatness. It was postulated that the reduction in SCFAs in the intestinal tracts of KI pigs may be associated with a reduction in Streptococcus spp. abundance. Compared to WT pigs, the concentration of fecal SCFAs in KI pigs was significantly reduced, which may be related to the decreased abundance of Streptococcus. The in vitro experiments showed that caproic acid could significantly enhance the differentiation efficiency of porcine SVF cells into mature adipocytes by activating the FFAR4 gene.

Recent advances in understanding the modulatory functions of gut and gut microbiota on human diseases facilitated our focused attention on the contribution of the gut to the pathophysiological alterations of many extraintestinal organs, including the liver, heart, brain, lungs, kidneys, bone, skin, reproductive, and endocrine systems. In this review, we applied the "gut-X axis" concept to describe the linkages between the gut and other organs and discussed the latest findings related to the "gut-X axis," including the underlying modulatory mechanisms and potential clinical intervention strategies.

Osteoarthritis (OA) is the most common chronic degenerative joint disease, characterized by cartilage damage, synovial inflammation, subchondral bone sclerosis, marginal bone loss, and osteophyte development. Clinical manifestations include inflammatory joint pain, swelling, osteophytes, and limitation of motion. The pathogenesis of osteoarthritis has not yet been fully uncovered. With ongoing research, however, it has been gradually determined that OA is not caused solely by mechanical injury or aging, but rather involves chronic low-grade inflammation, metabolic imbalances, dysfunctional adaptive immunity, and alterations in central pain processing centers. The main risk factors for OA include obesity, age, gender, genetics, and sports injuries. In recent years, extensive research on gut microbiota has revealed that gut dysbiosis is associated with some common risk factors for OA, and that it may intervene in its pathogenesis through both direct and indirect mechanisms. Therefore, gut flora imbalance as a pathogenic factor in OA has become a hotspot topic of research, with potential therapeutic connotations. In this paper, we review the role of the gut microbiota in the pathogenesis of OA, describe its relationship with common OA risk factors, and address candidate gut microbiota markers for OA diagnosis. In addition, with focus on OA therapies, we discuss the effects of direct and indirect interventions targeting the gut microbiota, as well as the impact of gut bacteria on the efficacy of OA drugs.

The primary source of short-chain fatty acids (SCFAs), now recognized as critical mediators of host health, particularly in the context of neurobiology and cancer development, is the gut microbiota's fermentation of dietary fibers. Recent research highlights the complex influence of SCFAs, such as acetate, propionate, and butyrate, on brain cancer progression. These SCFAs impact immune modulation and the tumor microenvironment, particularly in brain tumors like glioma. They play a critical role in regulating cellular processes, including apoptosis, cell differentiation, and inflammation. Moreover, studies have linked SCFAs to maintaining the integrity of the blood-brain barrier (BBB), suggesting a protective role in preventing tumor infiltration and enhancing anti-tumor immunity. As our understanding of the gut-brain axis deepens, it becomes increasingly important to investigate SCFAs' therapeutic potential in brain cancer management. Looking into how SCFAs affect brain tumor cells and the environment around them could lead to new ways to prevent and treat these diseases, which could lead to better outcomes for people who are dealing with these challenging cancers.

Traditionally, transformed cell line monolayers have been the standard model for studying epithelial barrier and transport function. Recently, intestinal organoids were proposed as superior in recapitulating the intestine. Typically, 3D organoids are digested and seeded as monolayers on gelatinous matrix pre-coated surfaces for anchorage. As this coat could potentially act as a diffusion barrier, we aimed to generate robust human duodenum-derived organoid monolayers that do not need a gelatinous matrix for anchorage to improve upon existing models to study epithelial transport and barrier function.

We characterized these monolayers phenotypically regarding polarization, tight junction formation and cellular composition, and functionally regarding uptake of nutrients, ion transport and cytokine-induced barrier dysfunction. The organoid monolayers recapitulated the duodenum phenotypically as well as functionally regarding glucose and short-chain fatty acid uptake. Tumour necrosis factor-alpha induced paracellular transport of 4-kDa Dextran and transcytosis of 44-kDa horseradish peroxidase. Notably, forskolin-stimulated chloride secretion was consistently lower when organoid monolayers were seeded on a layer of basement membrane extract (BME).

BME-free organoid monolayers represent an improved model for studying transcytotic, paracellular but especially transcellular transport. As BME is extracted from mice, our model furthers efforts to make organoid culture more animal-free.

Enteroendocrine cells (EECs) are a rare cell type of the intestinal epithelium. Various subtypes of EECs produce distinct repertoires of monoamines and neuropeptides which modulate intestinal motility and other physiologies. EECs also possess neuron-like properties, suggesting a potential vulnerability to ingested environmental neurotoxicants. One such group of toxicants are pyrethroids, a class of prevalent insecticides used residentially and agriculturally. Pyrethroids agonize voltage-gated sodium channels (VGSCs), inducing neuronal excitotoxicity, and affect the function of monoamine-producing neurons. Given their anatomical location at the interface with the environment and their expression of VGSCs, EECs likely represent a vulnerable cell-type to oral pyrethroid exposure. In this study, we used the EEC cell line, STC-1 cells, to evaluate the effects of the common pyrethroid deltamethrin on the functional status of EECs. We find that deltamethrin impacts both expression of serotonergic pathways and inhibits the adrenergic-evoked release of an EEC hormone, GLP-1, in vitro. In a mouse model of oral exposure, we found that deltamethrin induced an acute, yet transient, loss of intestinal motility, in both fed and fasted conditions. This constipation phenotype was accompanied by a significant decrease in peripheral serotonin production and an inhibition of nutrient-evoked intestinal hormone release. Together, these data demonstrate that deltamethrin alters monoaminergic signaling pathways in EECs and regulates intestinal motility. This work demonstrates a mechanistic link between pyrethroid exposure and intestinal impacts relevant to pyrethroid-associated diseases, including inflammatory bowel disease, neurodegenerative disease, and metabolic disorders.

Nowadays, obesity has become a major health issue. In addition to negatively affecting body composition and metabolic health, recent evidence shows unfavorable shifts in gut microbiota in individuals with obesity. However, the effects of weight loss on gut microbes and metabolites remain controversial. Therefore, the purpose of this study was to investigate the effects of a 12-week program on gut microbiota and metabolic health in patients with obesity.

We conducted a controlled trial in 23 male and female patients with obesity. Twelve participants completed a 12-week program of caloric restriction combined with strength and HIIT training (INT, pre-BMI 37.33 ± 6.57 kg/m2), and eleven participants were designated as non-intervention controls (pre-BMI 38.65 ± 8.07 kg/m2). Metagenomic sequencing of the V3-V4 region of the 16S rDNA gene from fecal samples allowed for gut microbiota classification. Nuclear magnetic resonance spectroscopy characterized selected serum and fecal metabolite concentrations.

Within INT, we observed a significant improvement in body composition; a significant decrease in liver enzymes (AST, ALT, and GMT); a significant increase in the relative abundance of the commensal bacteria (e.g., Akkermansia muciniphila, Parabacteroides merdae, and Phocaeicola vulgatus); and a significant decrease in the relative abundance of SCFA-producing bacteria (e.g., the genera Butyrivibrio, Coprococcus, and Blautia). In addition, significant correlations were found between gut microbes, body composition, metabolic health biomarkers, and SCFAs. Notably, the Random Forest Machine Learning analysis identified predictors (Butyrivibrio fibrisolvens, Blautia caecimuris, Coprococcus comes, and waist circumference) with a moderate ability to discriminate between INT subjects pre- and post-intervention.

Our results indicate that a 12-week caloric restriction combined with strength and HIIT training positively influences body composition, metabolic health biomarkers, gut microbiota, and microbial metabolites, demonstrating significant correlations among these variables. We observed a significant increase in the relative abundance of bacteria linked to obesity, e.g., Akkermansia muciniphila. Additionally, our study contributes to the ongoing debate about the role of SCFAs in obesity, as we observed a significant decrease in SCFA producers after a 12-week program.

The trial was registered on [05/12/2014] with ClinicalTrials.gov (No: NCT02325804).

Diabetic bone disease, a form of secondary osteoporosis, is characterized by weakened bones and an increased risk of fractures, especially in patients with type 2 diabetes (T2D). This review explores the key mechanisms driving this condition, including hyperglycemia, insulin resistance, advanced glycation end products (AGEs), and proinflammatory cytokines, all of which disturb normal bone turnover by disrupting the functions of osteoblasts and osteoclasts. We examine the roles of bone turnover and mineralization, as well as how microvascular complications affect bone microarchitecture. Additionally, the influence of gut hormones, such as GLP-1 and GIP, and gut microbiota, particularly species like Akkermansia muciniphila, on the gut-bone axis is discussed, as these factors play a role in regulating bone density and structure. While T2D patients may show normal or even elevated bone mineral density (BMD), the underlying quality of bone is often compromised, leading to increased fragility. This review integrates current knowledge on the molecular, hormonal, and microbial interactions contributing to diabetic bone disease. By highlighting these pathways, we aim to offer insights into potential therapeutic strategies and inform future research aimed at improving the diagnosis, treatment, and overall management of this condition.

The gut microbiota is an important factor responsible for the physiological processes as well as pathogenesis of host. The communication between central nervous system (CNS) and microbiota occurs by different pathways i.e., chemical, neural, immune, and endocrine. Alteration in gut microbiota i.e., gut dysbiosis causes alteration in the bidirectional communication between CNS and gut microbiota and linked to the pathogenesis of neurological and neurodevelopmental disorder. Therefore, now-a-days microbiota-gut-brain-axis (MGBA) has emerged as therapeutic target for the treatment of metabolic disorder. But, experimental data available on MGBA from basic research has limited application in clinical study. In present study we first summarized molecular mechanism of microbiota interaction with brain physiology and pathogenesis via collecting data from different sources i.e., PubMed, Scopus, Web of Science. Furthermore, evidence shows that adipose tissue (AT) is active during metabolic activities and may also interact with MGBA. Hence, in present study we have focused on the relationship among MGBA, brown adipose tissue, and white adipose tissue. Along with this, we have also studied functional specificity of AT, and understanding heterogeneity among MGBA and different types of AT. Therefore, molecular interaction among them may provide therapeutic target for the treatment of neurological disorder.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and seriously affects the quality of life of elderly patients. PD is characterized by the loss of dopaminergic neurons in the substantia nigra as well as abnormal accumulation of α-synuclein in neurons. Recent research has deepened our understanding of the gut microbiota, revealing that it participates in the pathological process of PD through the gut-brain axis, suggesting that the gut may be the source of PD. Therefore, studying the relationship between gut microbiota and PD is crucial for improving our understanding of the disease's prevention, diagnosis, and treatment. In this review, we first describe the bidirectional regulation of the gut-brain axis by the gut microbiota and the mechanisms underlying the involvement of gut microbiota and their metabolites in PD. We then summarize the different species of gut microbiota found in patients with PD and their correlations with clinical symptoms. Finally, we review the most comprehensive animal and human studies on treating PD through fecal microbiota transplantation (FMT), discussing the challenges and considerations associated with this treatment approach.

The rising prevalence of metabolic diseases, such as diabetes and obesity, presents a significant global health challenge. Dietary interventions, with their minimal side effects, hold great promise as effective strategies for blood sugar management. Highland barley (HB) boasts a comprehensive and unique nutritional composition, characterized by high protein, high fiber, high vitamins, low fat, low sugar, and diverse bioactive components. These attributes make it a promising candidate for alleviating high blood sugar. This review explores the mechanisms underlying the glucose-lowering properties of HB, emphasizing its nutritional profile and bioactive constituents. Additionally, it examines the impact of common HB processing techniques on its nutrient composition and highlights its applications in food products. By advancing the understanding of HB's value and mechanisms in diabetes prevention, this review aims to facilitate the development of HB-based foods suitable for diabetic patients.

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) play critical roles in co-ordinating postprandial metabolism, including modulation of insulin secretion and food intake. They are secreted from enteroendocrine cells in the intestinal epithelium following food ingestion, and act at multiple target sites including pancreatic islets and the brain. With the recent development of agonists targeting GLP-1 and GIP receptors for the treatment of type 2 diabetes and obesity, and the ongoing development of new incretin-based drugs with improved efficacy, there is great interest in understanding the physiology and pharmacology of these hormones.

Obesity is a complex disease that increases the risk of other pathologies. Its prevention and long-term weight loss maintenance are problematic. Gut microbiome is considered a potential obesity modulator. The objective of the present study was to summarize recent findings regarding the relationships between obesity, gut microbiota, and diet (vegetable/animal proteins, high-fat diets, restriction of carbohydrates), with an emphasis on dietary fiber and resistant starch. The composition of the human gut microbiome and the methods of its quantification are described. Products of the gut microbiome metabolism, such as short-chain fatty acids and secondary bile acids, and their effects on the gut microbiota, intestinal barrier function and immune homeostasis are discussed in the context of obesity. The importance of dietary fiber and resistant starch is emphasized as far as effects of the host diet on the composition and function of the gut microbiome are concerned. The complex relationships between human gut microbiome and obesity are finally summarized.

Type 2 diabetes (T2D) is a chronic metabolic disorder with a heterogeneous etiology encompassing societal and behavioral risk factors in addition to genetic and environmental susceptibility. The cardiovascular consequences of diabetes account for more than two-thirds of mortality among people with T2D. Not only does T2D shorten life expectancy, but it also lowers quality of life and is associated with extremely high health expenditures since diabetic complications raise both direct and indirect healthcare costs. An increasing body of research indicates a connection between T2D and gut microbial traits, as numerous alterations in the intestinal microorganisms have been noted in pre-diabetic and diabetic individuals. These include pro-inflammatory bacterial patterns, increased intestinal permeability, endotoxemia, and hyperglycemia-favoring conditions, such as the alteration of glucagon-like peptide-1 (GLP-1) secretion. Restoring microbial homeostasis can be very beneficial for preventing and co-treating T2D and improving antidiabetic therapy outcomes. This review summarizes the characteristics of a "diabetic" microbiota and the metabolites produced by microbial species that can worsen or ameliorate T2D risk and progression, suggesting gut microbiota-targeted strategies to restore eubiosis and regulate blood glucose. Nutritional supplementation, diet, and physical exercise are known to play important roles in T2D, and here their effects on the gut microbiota are discussed, suggesting non-pharmacological approaches that can greatly help in diabetes management and highlighting the importance of tailoring treatments to individual needs.

The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes and enzymes for microbial and host-produced compounds, establishing a symbiotic link between the external environment and the host at both the gut and systemic levels. The gut microbiome, which is primarily made up of commensal bacteria, is critical for maintaining the healthy host's immune system, aiding digestion, synthesizing essential nutrients, and protecting against pathogenic bacteria, as well as influencing endocrine, neural, humoral, and immunological functions and metabolic pathways. Qualitative, quantitative, and/or topographic shifts can alter the gut microbiome, resulting in dysbiosis and microbial dysfunction, which can contribute to a variety of noncommunicable illnesses, including hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel disease, cancer, and irritable bowel syndrome. While most evidence to date is observational and does not establish direct causation, ongoing clinical trials and advanced genomic techniques are steadily enhancing our understanding of these intricate interactions. This review will explore key aspects of the relationship between gut microbiota, eubiosis, and dysbiosis in human health and disease, highlighting emerging strategies for microbiome engineering as potential therapeutic approaches for various conditions.

Energy-dense foods are commonly rich in fat and simple sugars and poor in dietary fiber and micronutrients; regularly consuming them decreases the concentration and/or effect of anorexigenic hormones and may increase that of orexigenic ones, thereby decreasing satiety. In contrast, plant-derived phenolic-rich foods exert positive effects on satiety. In silico, in vitro, and in vivo investigations on some of most representative phenolic acids like chlorogenic acid (CGA), gallic acid (GA), ferulic acid (FA), and protocatechuic acid (PCA) have shown that they are able to modulate various hunger and satiety processes; however, there are few studies that show how their chemical structure contributes to achieve such effects. The objective of this review is to summarize how these phenolic acids can favorably modulate hormones and other satiety mediators, with emphasis on the chemical interactions exerted between the core of these compounds and their biological targets. The evidence suggests that they form interactions with certain hormones, their receptors, and/or enzymes involved in regulating hunger and satiety, which are attributed to their chemical structure (such as the position of hydroxyl groups). Further research is needed to continue understanding these molecular mechanisms of action and to utilize the knowledge in the development of health-promoting foods.

The gut is traditionally recognized as the central organ for the digestion and absorption of nutrients, however, it also functions as a significant endocrine organ, secreting a variety of hormones such as glucagon-like peptide 1, serotonin, somatostatin, and glucocorticoids. These gut hormones, produced by specialized intestinal epithelial cells, are crucial not only for digestive processes but also for the regulation of a wide range of physiological functions, including appetite, metabolism, and immune responses. While gut hormones can exert systemic effects, they also play a pivotal role in maintaining local homeostasis within the gut. This review discusses the role of the gut as an endocrine organ, emphasizing the stimuli, the newly discovered functions, and the clinical significance of gut-secreted hormones. Deciphering the emerging role of gut hormones will lead to a better understanding of gut homeostasis, innovative treatments for disorders in the gut, as well as systemic diseases.

The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.

Multiple studies over the last decade have established that Alzheimer's disease and related dementias (ADRD) are associated with changes in the gut microbiome. These alterations in organismal composition result in changes in the abundances of functions encoded by the microbial community, including metabolic capabilities, which likely impact host disease mechanisms. Gut microbes access dietary components and other molecules made by the host and produce metabolites that can enter circulation and cross the blood-brain barrier (BBB). In recent years, several microbial metabolites have been associated with or have been shown to influence host pathways relevant to ADRD pathology. These include short chain fatty acids, secondary bile acids, tryptophan derivatives (such as kynurenine, serotonin, tryptamine, and indoles), and trimethylamine/trimethylamine N-oxide. Notably, some of these metabolites cross the BBB and can have various effects on the brain, including modulating the release of neurotransmitters and neuronal function, inducing oxidative stress and inflammation, and impacting synaptic function. Microbial metabolites can also impact the central nervous system through immune, enteroendocrine, and enteric nervous system pathways, these perturbations in turn impact the gut barrier function and peripheral immune responses, as well as the BBB integrity, neuronal homeostasis and neurogenesis, and glial cell maturation and activation. This review examines the evidence supporting the notion that ADRD is influenced by gut microbiota and its metabolites. The potential therapeutic advantages of microbial metabolites for preventing and treating ADRD are also discussed, highlighting their potential role in developing new treatments.

Excessive body weight is associated with many chronic metabolic diseases and weight loss, so far, remains the gold standard treatment. However, despite tremendous efforts exploring optimal treatments for obesity, many individuals find losing weight and maintaining a healthy body weight difficult. Weight loss is often not sustainable resulting in weight regain and subsequent efforts to lose weight. This cyclic pattern of weight loss and regain is termed "yoyo dieting" and predisposes individuals to obesity and metabolic comorbidities. How yoyo dieting might worsen obesity complications during the weight recurrence phase remains unclear. In particular, there is limited data on the role of the gut microbiome in yoyo dieting. Gut health distress, especially gut inflammation and microbiome perturbation, is strongly associated with metabolic dysfunction and disturbance of energy homeostasis in obesity. In this review, we summarise current evidence of the crosstalk between the gastrointestinal system and energy balance, and the effects of yoyo dieting on gut inflammation and gut microbiota reshaping. Finally, we focus on the potential effects of post-dieting weight loss in improving gut health and identify current knowledge gaps within the field, including gut-derived peptide hormones and their potential suitability as targets to combat weight regain, and how yoyo dieting and associated changes in the microbiome affect the gut barrier and the enteric nervous system, which largely remain to be determined.

Traditional Chinese medical literature contains numerous records of many traditional Chinese herbal medicines that exhibit efficacy in enhancing resistance to cold, yet there is a lack of scientific explanation. Lycium barbarum is among the herbal medicines that are explicitly documented to enhance resistance to cold in the "Ben Cao Gang Mu (Compendium of Materia Medica)". Herein, we investigated L. barbarum polysaccharide (LBP)-induced browning of inguinal white adipose tissue (iWAT), energy expenditure and thermogenic function in a long-term (4 months) treatment mouse model. LBP supplementation resulted in a significant reduction in weight and adipocyte size in iWAT, along with increased gut microbiota diversity. Specifically, the levels of Lachnospiraceae, Ruminococcaceae and Bacteroidaceae (short-chain fatty acid-producing bacteria) were elevated, leading to a higher level of short-chain fatty acids (SCFAs) in the caecal content. These effects subsequently triggered the release of glucagon-like peptide-1 (GLP-1) and activated the CREB/PGC1α signaling pathway in iWAT, thereby increasing energy expenditure and enhancing thermogenic function. The antibiotic treatment experiments confirmed that the LBP-mediated gut microbiota participated in the process of iWAT browning. In summary, our findings provide the first scientific explanation and mechanistic insights into the cold resistance of L. barbarum and identify potentially safe natural product supplements for individuals in alpine areas.