Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding Porphyromonadaceae, Campylobacteraceae, Prevotellaceae, Actimomycetaceae, Veillonellaceae, Anaerivoracaceae, Fusobacteriaceae, and the Clostridium family XI 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while Pseudomonadaceae and Micrococcacecae, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5-10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.

Metabolic syndrome (MetS) is a disease with complex and diverse etiologies. Extrinsic factors such as diet and lifestyle can induce dysbiosis of gut microbes, compromising intestinal barrier integrity and leading to inflammation and insulin resistance, thereby advancing MetS. Probiotic interventions have shown potential in ameliorating gut microbiota dysbiosis and regulating host metabolism by assimilating lipids, metabolizing carbohydrates, and producing short-chain fatty acids (SCFA), indole compounds, secondary bile acids, conjugated linoleic acid (CLA), and other active ingredients. An increasing number of new strains are being isolated and validated for their effective roles intervening on MetS in animal and population studies. This review aims to provide updated insights into the pathogenic mechanisms of MetS, highlight the newly identified probiotic strains that have demonstrated improvements in MetS, and elucidate their mechanisms of action, with the aim of offering contemporary perspectives for the future use of probiotics in mitigating MetS.

Polysaccharides from valuable mushroom Pleurotus citrinopileatus (PCP) have been considered to have health promoting effects. In this study, two main polysaccharides components with different molecular weights were isolated (PCP40 with 1000 kDa and PCP80 with 10 kDa, PCPs) and their anti-obesity effects were evaluated and compared. Results showed that PCPs could correct the abnormity of lipid and sugar metabolism, indicating by the decreased level of body weight, white fat weight, adipocyte size, serum lipid as well as the recovery of leptin resistance and insulin resistance in high-fat diet (HFD) mice. PCP40 exerted more remarkable lipid lowering effects than PCP80, which might due to its higher fat binding and pancreatic lipase inhibition capacity that inhibit lipid absorption, and the more active lipolysis activity. On the other hand, PCPs improved intestinal microecology and alleviate chronic inflammation in HFD mice. PCPs could promote SCFAs production and recover gut hypoxic condition through repairing the function of mitochondria. This changed condition also led to the increase of bacterial variety and distinct bacteria enrichment, such as Paracteroides goldsteinii (PCP40) and Lactobacillus (PCP80). These findings suggested PCPs, especially the high molecular component PCP40, had a promising anti-obesity effect.

The gut-brain axis (GBA) is a bidirectional communication network between the gastrointestinal tract and the brain, modulated by gut microbiota and related biomarkers. Malnutrition disrupts GBA homeostasis, exacerbating GBA dysfunction through gut dysbiosis, impaired neuroactive metabolite production, and systemic inflammation. Nutraceuticals, including probiotics, prebiotics, synbiotics, postbiotics, and paraprobiotics, offer a promising approach to improving GBA homeostasis by modulating the gut microbiota composition and related neuroactive metabolites. This review aims to elucidate the interplay between gut microbiota-derived biomarkers and GBA dysfunction in malnutrition and evaluate the potential of nutraceuticals in combating malnutrition. Furthermore, it explores the future of personalised nutraceutical interventions tailored to individual genetic and microbiome profiles, providing a targeted approach to optimise health outcomes. The integration of nutraceuticals into GBA health management could transform malnutrition treatment and improve cognitive and metabolic health.

Research has established links between the gut microbiome (GM) and both obesity and type 2 diabetes (T2D), which is much discussed, but underexplored. This study employed body mass index (BMI) as the measurement of obesity to delve deeper into the correlations from a genetic perspective.

We performed the Mendelian randomization (MR) analysis to examine the causal effects of GM on T2D and BMI, and vice versa. Genome-wide association study (GWAS) summary datasets were utilized for the analysis, including T2D (N = 933,970), BMI (N = 806,834), and two GM datasets from the international consortium MiBioGen (211 taxa, N = 18,340) and the Dutch Microbiome Project (DMP) (207 taxa, N = 7,738). These datasets mainly cover European populations, with additional cohorts from Asia and other regions. To further explore the potential mediating role of GM in the connections between BMI and T2D, their interaction patterns were summarized into a network.

MR analysis identified 9 taxa that showed protective properties against T2D. Seven species were within the Firmicutes and Bacteroidales phyla in the DMP, and two were from the MiBioGen (Odds Ratio (OR): 0.94-0.95). Conversely, genetic components contributing to the abundance of 12 taxa were associated with increased risks of T2D (OR: 1.04-1.12). Furthermore, T2D may elevate the abundance of seven taxa (OR: 1.03-1.08) and reduce the abundance of six taxa (OR: 0.93-0.97). In the analysis of the influence of the genetic component of BMI on GM composition, BMI affected 52 bacterial taxa, with 28 decreasing (OR: 0.75-0.92) and 24 increasing (OR: 1.08-1.27). Besides, abundances of 25 taxa were negatively correlated with BMI (OR: 0.95-0.99), while positive correlations were detected for 14 taxa (OR: 1.01-1.05). Notably, we uncovered 11 taxa genetically associated with both BMI and T2D, which formed an interactive network.

Our findings provide evidence for the GM-mediated links between obesity and T2D. The identification of relevant GM taxa offers valuable insights into the potential role of the microbiome in these diseases.

Background: Probiotics alter gut microbiota and have beneficial effects on immune homeostasis. The role of probiotics in diabetes has been shown in some studies. Interleukin (IL)-21 and IL-22 have been implicated in the pathogenesis of type 1 diabetes mellitus (T1DM). Objectives: This study aimed to assess the effect of oral supplementation with probiotics on glycemic control and IL-21 and IL-22 levels in pediatric patients with T1DM. Methods: This randomized controlled trial was registered in ClinicalTrials (NCT04579341) and included 70 children and adolescents with T1DM. They were randomly assigned into two groups to receive either an oral probiotic tablet containing 0.5 mg Lactobacillus acidophilus once daily or a matching placebo. Both groups were followed up for 6 months with assessment of fasting blood glucose (FBG), lipids, hemoglobin A1c (HbA1c), and IL-21 and IL-22 levels. Results: Baseline clinical characteristics and laboratory parameters were similar between both groups (p > 0.05). After six months, probiotic supplementation for the intervention group resulted in significant decreases in FBG, HbA1c, total cholesterol, and IL-21 levels, while IL-22 was increased compared with baseline levels (p < 0.001) and compared with the placebo group (p < 0.001). No adverse reactions were reported. Baseline IL-21 was positively correlated to FBG, HbA1c, and total cholesterol while there were negative correlations between these variables and IL-22 levels. Conclusions: Probiotic supplementation improved glucose homeostasis and glycemic control, possibly through their immunomodulatory effects on cytokines IL-21 and IL-22. Thus, probiotics could be a safe adjuvant therapy to intensive insulin in pediatric patients with T1DM.

Radix Rehmanniae (RR) is a widely used herb in traditional Chinese Medicine with properties of tonifying the kidneys and nourishing the blood. Both raw and processed RR are effective for the treatment of diabetes in clinical practice. Oligosaccharides and iridoid glycosides are the primary active components responsible for the anti-diabetic effects of RR. In this study, a rapid and sensitive hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method was developed for simultaneous determination of oligosaccharides (raffinose, manninotriose and stachyose) and iridoid glycosides (catalpol and ajugol) in rat plasma. Significant analytical challenges were encountered during method development, including distinct retention behaviors of oligosaccharides and iridoid glycosides, low ionization and extraction efficiency of oligosaccharides, thermal instability of catalpol and reduced column performance. The strategies to overcome these challenges were presented by optimizing chromatographic separation, mass spectrometric detection and sample preparation. The best separation was achieved using an Accucore-150-Amide-HILIC column (100 mm × 2.1 mm, 2.6 μm) at 50 °C with mobile phase consisted of acetonitrile and ammonium acetate (2.5 mM) under gradient elution. Ammonium adduct ions produced by positive electrospray ionization were chosen as precursor ions for multiple reaction monitoring transitions. The established HILIC-MS/MS method exhibited good linearity (r > 0.9937) with the lower limits of quantification of 0.01-0.2 μg/mL using only 50 µL of plasma sample. The method was successfully applied to pharmacokinetic characterization of oligosaccharides and iridoid glycosides in normal and type 2 diabetic rats following intragastric administration of raw and processed RR extracts.

High fructose diet (HFrD) has been approved to be involved in the pathogenesis of insulin resistance. Mesenchymal stem cells have a vital role in the treatment of various diseases including metabolic disturbances. We investigated the effect of Adipose-derived mesenchymal stem cells (ADMSCs) against HFrD-induced metabolic disorders and the molecular mechanisms for this effect. Rats were divided into 3 groups; control, HFrD, and combined HFrD with ADMSCs. We assessed liver functions, gut microbiota activity, oxidative stress, adiponectin, and IL10 levels. Also, we measured SREBP-1, IRS-1 expression using Western blot, and Malat1 expression using rt-PCR. ADMSCs antagonized metabolic abnormalities induced by HFrD in the form of improvement of liver functions and alleviation of oxidative stress. In addition, ADMSCs ameliorated gut microbiota activity besides the elevation of adiponectin and IL10 levels. ADMSCs attenuated insulin resistance through upregulation of IRS1 and downregulation of SREBP-1 and Malat1. ADMSCs can protect against HFrD-induced metabolic hazards.

Aging is associated with immune senescence and gut dysbiosis, both of which are heavily influenced by the diet. In this review, we summarize current knowledge regarding the impact of diets high in fiber, protein, or fat, as well as different dietary components (tryptophan, omega-3 fatty acids, and galacto-oligosaccharides) on the immune system and the gut microbiome in aging. Additionally, this review discusses how aging alters tryptophan metabolism, contributing to changes in immune function and the gut microbiome. Understanding the relationship between diet, the gut microbiome, and immune function in the context of aging is critical to formulate sound dietary recommendations for older individuals, and these personalized nutritional practices will ultimately improve the health and longevity of the elderly.

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.

Takeda G protein-coupled receptor 5 (TGR5), also known as G protein-coupled bile acid receptor 1 (GPBAR1), is a cell surface receptor involved in key physiological processes, including glucose homeostasis and energy metabolism. Recent research has focused on the role of TGR5 activation in preventing or treating diabetes while also highlighting its potential impact on the progression of diabetic complications. Functional foods and edible plants have emerged as valuable sources of natural compounds that can activate TGR5, offering potential therapeutic benefits for diabetes management. Despite growing interest, studies on the activation of TGR5 by dietary bioactive compounds remain scattered. This Review aims to provide a comprehensive analysis of how dietary bioactives act as potential agents for TGR5 activation in managing diabetes and its complications. It explores the mechanisms of TGR5 activation through both direct agonistic effects and indirect pathways via modulation of the gut microbiota and bile acid metabolism.

Recent studies have emphasized the relationship between mental health and the human intestine microbiota. In this study, we evaluate the effect of consuming Biotics, on levels of depression, anxiety, and cognitive function.

This meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. We searched MEDLINE (PubMed), Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov. All full-text articles and major reviews were manually searched for additional studies.

The initial analysis was based on the concept that consuming Biotics causes changes in anxiety, measured using various instruments. This analysis showed that consuming Biotics significantly reduced anxiety in our study participants (SMD = 0.2894, Z = 2.46, P = 0.0139, I^2 = 92.4%). The meta-analysis included 4295 samples (2194 in the experimental group and 2101 in the control group). In terms of depression, the analysis showed that consuming Biotics significantly reduced depression in our study participants (SMD = 0.2942, Z = 2.13, P = 0.0335, I^2 = 91.7%). The meta-analysis included 3179 samples (1603 in the experimental group and 1576 in the control group). Regarding cognitive function, the analysis showed that consuming Biotics significantly improved cognitive function in our study participants (SMD = 0.4819, Z = 3.00, P = 0.0027, I^2 = 77.9%). The meta-analysis included 915 samples (470 in the experimental group and 445 in the control group).

Our results indicate that most recent studies support the effectiveness of probiotics in reducing symptoms of anxiety, depression, and cognitive issues despite some discrepancies in the findings. People with mild symptoms may experience greater benefits from taking probiotics.

PROSPERO registration ID: CRD42024589507.

The gut microbiota, the complex community of microorganisms that inhabit the gastrointestinal tract, has emerged as a key player in the pathogenesis of neurodegenerative disorders, including Alzheimer's disease (AD). AD is characterized by progressive cognitive decline and neuronal loss, associated with the accumulation of amyloid-β plaques, neurofibrillary tangles, and neuroinflammation in the brain. Increasing evidence suggests that alterations in the composition and function of the gut microbiota, known as dysbiosis, may contribute to the development and progression of AD by modulating neuroinflammation, a chronic and maladaptive immune response in the central nervous system. This review aims to comprehensively analyze the current role of the gut microbiota in regulating neuroinflammation and glial cell function in AD. Its objective is to deepen our understanding of the pathogenesis of AD and to discuss the potential advantages and challenges of using gut microbiota modulation as a novel approach for the diagnosis, treatment, and prevention of AD.

Excessive salt intake has been associated with gut dysbiosis and increased cardiovascular risk. This study investigates the role of gut dysbiosis induced by a high-salt diet in the progression of atherosclerosis in ApoE-deficient mice. Sixteen-week-old male ApoE-deficient mice were fed either a high-fat, high-sucrose diet or high-fat, high-sucrose diet supplemented with 4% NaCl for eight weeks. The group on the HFHSD with high salt showed significant progression of atherosclerosis compared to the high-fat, high-sucrose diet group. Analysis of the gut microbiota revealed reduced abundance of beneficial bacteria such as Allobaculum spp., Lachnospiraceae, and Alphaproteobacteria in the high-salt group. Additionally, this group exhibited increased expression of the Cd36 gene, a transporter of long-chain fatty acids, in the small intestine. Serum and aortic levels of saturated fatty acids, known contributors to atherosclerosis, were markedly elevated in the high-salt group. These findings suggest that a high-salt diet exacerbates atherosclerosis by altering gut microbiota and increasing the absorption of saturated fatty acids through upregulation of intestinal fatty acid transporters. This study provides new insights into how dietary salt can influence cardiovascular health through its effects on the gut microbiome and lipid metabolism.

This review discusses findings related to neurological disorders, gut microbiota, and bariatric surgery, focusing on neurotransmitters, neuroendocrine, the pathophysiology of bacteria contributing to disorders, and possible therapeutic interventions. Research on neurotransmitters suggests that their levels are heavily influenced by gut microbiota, which may link them to neurological disorders such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Depression, and Autism spectrum disorder. The pathophysiology of bacteria that reach and influence the central nervous system has been documented. Trends in microbiota are often observed in specific neurological disorders, with a prominence of pro-inflammatory bacteria and a reduction in anti-inflammatory types. Furthermore, bariatric surgery has been shown to alter microbiota profiles similar to those observed in neurological disorders. Therapeutic interventions, including fecal microbiota transplants and probiotics, have shown potential to alleviate neurological symptoms. We suggest a framework for future studies that integrates knowledge from diverse research areas, employs rigorous methodologies, and includes long-trial clinical control groups.

Intestinal probiotics significantly regulate the growth performance of their host, with their composition being influenced by various factors. While many studies have explored how gut microbiota composition affects growth traits such as body weight and BMI, the research on probiotics influenced by host genetic factors, and their subsequent impact on host growth performance, remains limited. To address this research gap, we collected fecal and tissue samples, as well as phenotypic data, from 193 Yunong black pigs at 280 days of age. We then sequenced and genotyped all 193 subjects using the 50K SNP BeadChip, yielding a comprehensive dataset for genetic and microbiome analyses. We then employed microbiome-wide association studies (MWAS), a meta-analysis, and microbiome-wide genetic association studies (MGWASs) to examine the relationship between host genetics, gut microbiota, and growth performance. Four key microbial taxa, namely Coprococcus, Blautia, Ruminococcaceae, and RF16, were identified as being significantly associated with body weight and BMI. The MGWAS analysis revealed that both Coprococcus and Ruminococcaceae were significantly associated with host genomic variations. A total of four important single nucleotide polymorphisms (SNPs) were mapped to two chromosomal regions, corresponding to three candidate genes. Among them, the candidate genes INPP4B, SCOC, and PABPC4L were identified as being related to the abundance of key microbes. This study provides new insights into the joint contributions of host genetics and probiotics to host growth traits, offering theoretical guidance and data support for the development of efficient and targeted breeding strategies.

Metabolic syndrome (Mets) is an important contributor to morbidity and mortality in cardiovascular, liver, neurological, and reproductive diseases. Short-chain fatty acid (SCFA), an organismal energy donor, has recently been demonstrated in an increasing number of studies to be an important molecule in ameliorating immuno-inflammation, an important causative factor of Mets, and to improve lipid distribution, blood glucose, and body weight levels in animal models of Mets. This study reviews recent research advances on SCFA in Mets from an immune-inflammatory perspective, including complications dominated by chronic inflammation, as well as the fact that these findings also contribute to the understanding of the specific mechanisms by which gut flora metabolites contribute to metabolic processes in humans. This review proposes an emerging role for SCFA in the inflammatory Mets, followed by the identification of major ambiguities to further understand the anti-inflammatory potential of this substance in Mets. In addition, this study proposes novel strategies to modulate SCFA for the treatment of Mets that may help to mitigate the prognosis of Mets and its complications.

In recent years, the role of the microbiome-gut-brain axis in the pathogenesis of Alzheimer's disease (AD) has garnered increasing attention. Specifically, tryptophan metabolism via the kynurenine pathway (KP) plays a crucial regulatory role in this axis. This study reviews how exercise regulates the microbiome-gut-brain axis by influencing kynurenine pathway metabolism, thereby exerting resistance against AD. This paper also discusses how exercise positively impacts AD via the microbiome-gut-brain axis by modulating the endocrine, autonomic nervous, and immune systems. Although the specific mechanisms are not fully understood, research indicates that exercise may optimize tryptophan metabolism by promoting the growth of beneficial microbiota and inhibiting harmful microbiota, producing substances that are beneficial to the nervous system and combating AD. The aim of this review is to provide new perspectives and potential intervention strategies for the prevention and treatment of AD by exploring the links between exercise, KP and the gut-brain axis.

The small intestine, including the endocannabinoid system (ECS), regulates the energy homeostasis. If maternal obesity modifies the intestinal ECS of the offspring favoring metabolic disorders throughout life is unexplored. Regardless maternal insults, overaction of the ECS has been related to obesity, mainly via type 1 cannabinoid receptor (CB1) signaling, while type 2 cannabinoid receptor (CB2) signaling and the endocannabinoid-like compounds, such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), have been associated with anti-inflammatory effects. We hypothesized that maternal obesity changes the ECS in the small intestine of weanling rat offspring in a sex-specific manner associated with altered fecal metabolites. Female rats received a control diet (C; 9% fat) or an obesogenic diet (OD; 37.2% fat, 11.8% sucrose) 9 weeks before mating, gestation and lactation. Offspring were euthanized at weaning. Maternal obesity increased CB2 protein content and mRNA levels of monocyte chemoattractant protein-1 in the small intestine in male offspring, while decreased fecal content of PEA and OEA in both sexes. Maternal obesity decreased gut permeability, but impaired glycemic homeostasis. Concerning fecal levels of γ-aminobutyric acid, amino acids and hypoxanthine, maternal obesity induced a fecal signature related to inflammatory and glycemic homeostasis impairment and dysbiosis. Maternal obesity induced intestinal inflammation and the signaling of CB2, PEA, and OEA might be part of a counter-regulatory response, contributing to reduced gut permeability, but not enough to avoid overweight and glycemic impairment in the offspring at weaning. Our findings provide molecular insights into the intestinal and fecal biomarkers for metabolic disorders.

The benefits of probiotics/prebiotics consumption on chronic kidney disease (CKD) and mortality remains controversial.

This study investigates the association of probiotics/prebiotics consumption with chronic kidney disease (CKD) and mortality.

Clinical data were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2005-2016 database. Weighted multivariable logistic and liner regression models, cox proportional hazards models and stratified analysis were used to analyse the relationships between consumption of probiotics/prebiotics, renal parameters, CKD and mortality. We also conducted a two-sample Mendelian randomization (MR) analysis of single nucleotide polymorphisms (SNPs) related to different genera of gut microbiota to assess their causal relationships with CKD and mortality.

15,291 subjects were analysed (897 with consumption of probiotics/prebiotics and 14,394 without). The use of probiotics/prebiotics showed an inverse correlation with urinary albumin-to-creatinine ratio (UACR) (P < 0.05). Probiotics/prebiotics use was associated with lower risk of CKD in subjects with hypertension, hyperlipidaemia and diabetes mellitus. The consumption of probiotics/prebiotics was associated with a significantly lower risk of all-cause mortality in different regression models (P < 0.001, for all), but the lower risk of cardiovascular mortality did not reach statistical significance (P > 0.05, for all)]. MR analysis showed negative associations between the genetically predicted genus Flavonifractor and risk of CKD and diabetic kidney disease (DKD).

After multivariable regression, and cox proportional hazards analysis, we found that the use of probiotics/prebiotics was associated with improved kidney and mortality outcomes in the general population from NHANES database. The two-sample MR analysis provided further genetic evidence that a distinct genus of gut microbiota was associated with reduced risk of CKD, DKD and mortality.

A US Food and Drug Administration-approved new bromodomain (BRD) and extraterminal (BET) bromine domain antagonist called apabetalone, which targets BRD4, has been shown to increase prebeta-1 high-density lipoprotein (HDL) particles, enhance apolipoprotein A-I in both humans and animals, and restore angiogenesis in experimental diabetes. Its action is not however fully known mechanistically. The objective of our research was to investigate the impact of apabetalone on renal damage linked to diabetic kidney disease (DKD).

This research employed both pharmacological and genetic methods to examine the impact of apabetalone on db/db (BKS. Cg-leprdb/leprdb) mice and human tubular epithelial cells (HK-2).

Here, significant reductions in blood creatinine, urea nitrogen, and urinary albumin-to-creatinine ratio (UACR) levels, serum triglycerides (TGs) and serum total cholesterol (TC), as well as ectopic lipid droplet formation in renal tissue, were seen in the db/db mice following apabetalone therapy. Analysis of the gut microbiota revealed changes in its composition. Significantly, the proportion of Firmicutes to Bacteroidetes decreased, as well as Deferribacterota, indicating a positive influence on lipid metabolism. Untargeted metabolomic analysis indicated that the ABC transporter signaling pathway, implicated in cholesterol metabolism, was enriched. Moreover, peroxisome proliferator-activated receptor gamma (PPARγ)/liver X receptor (LXR)/adenosine triphosphate-binding cassette transporter A1 (ABCA1) protein, and mRNA level, as well as fibrosis-related marker proteins, fibronectin and collagen I were all improved by apabetalone.

Therefore, we suggest that apabetalone showed significant antihyperlipidemic and antifibrotic effects, closely associated with alterations in the gut microbiota and cholesterol metabolism. The results of this investigation provide fresh perspectives on the processes that underlie apabetalone's effects in db/db mice.

Metabolic abnormalities associated with excess adiposity in obesity contribute to many noncommunicable diseases, including sarcopenic obesity. Sarcopenic obesity is the loss of muscle mass coupled with excess fat mass and fatty infiltrations in muscle tissue called myosteatosis. A diet-induced obesity model was developed to study fat infiltration in muscle tissue. Only male rats have been considered in these investigations neglecting that female rats might respond differently. The objective of this study was to determine if the response to diet-induced obesity can be generalized to both sexes, or whether sex affects the response to the HFS diet, as indicated by markers of metabolic syndrome and changed in muscle integrity. Using a combination of histological staining techniques, quantitative proteomics, and measures of metabolic syndrome and inflammation, it was determined that the diet-induced obesity model in female Sprague-Dawley rats is a viable model with pronounced effects on the musculoskeletal system. We found sex-dependent and muscle-specific differences in intramuscular fat infiltration between male and female rats receiving the obesogenic diet. Including females in research may allow for identifying distinct causes of the mechanistic relationship between diet, obesity, metabolic syndrome, and the sex-dependent differential effects of these factors on adaptation and degeneration of musculoskeletal tissues.

Since diet is a known modulator of inflammation, the Dietary Inflammatory Index (DII), which quantifies the inflammatory potential of an individual's diet, becomes a significant parameter to consider. Chronic diarrhea is commonly linked to inflammatory processes within the gut. Thus, this study aimed to explore the potential link between DII and chronic diarrhea.

This research utilized data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. The DII was calculated according to the average intake of 28 nutrients using information gathered from two 24-hour recall interviews. The Bristol Stool Form Scale (BSFS) was adopted to describe chronic diarrhea, identifying stool Type 6 and Type 7. Multivariate logistic regression models examined the causal connection between DII and chronic diarrhea. Additionally, subgroup analyses and interaction tests were conducted.

The study encompassed 11,219 adults, among whom 7.45% reported chronic diarrhea. Initially, multivariate logistic regression analysis revealed a positive association between DII and chronic diarrhea. Nevertheless, this connection lost statistical significance (OR = 1.00; 95% CI, 0.96-1.05; P = 0.8501) after adjusting for all confounding variables. Stratified by sex, the analysis revealed a notable rise in the risk of chronic diarrhea with increasing DII among female participants (all P for trend < 0.05). This tendency remained constant even after full adjustment (P for trend = 0.0192), whereas no significant association was noted in males (all P for trend > 0.05). Furthermore, an L-shaped association emerged between DII and chronic diarrhea, with an inflection point of -1.34. In the population with DII scores below -1.34, each unit increase in DII correlated with a 27% reduction in the probability of chronic diarrhea (OR = 0.73; 95% CI, 0.57-0.93), whereas in the population with DII scores above -1.34, the risk increased by 4% (OR = 1.04; 95% CI, 0.98-1.10). Merely, the gender interaction was shown to be statistically significant based on subgroup analyses and interaction tests.

A favorable association between DII and chronic diarrhea exists in adults in the United States. Nevertheless, additional long-term prospective studies are required to confirm and solidify those findings.

Bariatric surgery is an effective treatment for type 2 Diabetes Mellitus (T2DM), yet the precise mechanisms underlying its effectiveness remain incompletely understood. While previous research has emphasized the role of rearrangement of the gastrointestinal anatomy, gaps persist regarding the specific impact on the gut microbiota and barriers within the biliopancreatic, alimentary, and common limbs. This study aimed to investigate the effects of duodenal-jejunal bypass (DJB) surgery on obese T2DM mice. We performed DJB and SHAM surgery in obese T2DM mice to investigate changes in the gut microbiota and barrier across different intestinal limbs. The effects on serum metabolism and potential associations with T2DM improvement were also investigated. Following DJB surgery, there was an increased abundance of commensals across various limbs. Additionally, the surgery improved intestinal permeability and inflammation in the alimentary and common limbs, while reducing inflammation in the biliopancreatic limbs. Furthermore, DJB surgery also improved T2DM by increasing L-glutamine, short-chain fatty acids, and bile acids and decreasing branched-chain amino acids. This study underscores the role of intestinal rearrangement in reshaping gut microbiota composition and enhancing gut barrier function, thereby contributing to the amelioration of T2DM following bariatric surgery, and providing new insights for further research on bariatric surgery.

It is critical to sustain the diversity of the microbiota to maintain host homeostasis and health. Growing evidence indicates that changes in gut microbial biodiversity may be associated with the development of several pathologies, including type 2 diabetes mellitus (T2DM). Metformin is still the first-line drug for treatment of T2DM unless there are contra-indications. The drug primarily inhibits hepatic gluconeogenesis and increases the sensitivity of target cells (hepatocytes, adipocytes and myocytes) to insulin; however, increasing evidence suggests that it may also influence the gut. As T2DM patients exhibit gut dysbiosis, the intestinal microbiome has gained interest as a key target for metabolic diseases. Interestingly, changes in the gut microbiome were also observed in T2DM patients treated with metformin compared to those who were not. Therefore, the aim of this review is to present the current state of knowledge regarding the association of the gut microbiome with the antihyperglycemic effect of metformin. Numerous studies indicate that the reduction in glucose concentration observed in T2DM patients treated with metformin is due in part to changes in the biodiversity of the gut microbiota. These changes contribute to improved intestinal barrier integrity, increased production of short-chain fatty acids (SCFAs), regulation of bile acid metabolism, and enhanced glucose absorption. Therefore, in addition to the well-recognized reduction of gluconeogenesis, metformin also appears to exert its glucose-lowering effect by influencing gut microbiome biodiversity. However, we are only beginning to understand how metformin acts on specific microorganisms in the intestine, and further research is needed to understand its role in regulating glucose metabolism, including the impact of this remarkable drug on specific microorganisms in the gut.

There is scattered information in the scientific literature regarding the characterization of probiotic bacteria found in fermented milk beverages and the beneficial effects of probiotic bacteria on human health. Our objective was to gather the available information on the use of probiotic bacteria in the prevention of civilization diseases, with a special focus on the prevention of obesity, diabetes, and cancer.

We carried out a literature review including the following keywords, either individually or collectively: lactic acid bacteria; probiotic bacteria; obesity; lactose intolerance; diabetes; cancer protection; civilization diseases; intestinal microbiota; intestinal pathogens.

This review summarizes the current state of knowledge on the use of probiotic bacteria in the prevention of civilization diseases. Probiotic bacteria are a set of living microorganisms that, when administered in adequate amounts, exert a beneficial effect on the health of the host and allow for the renewal of the correct quantitative and qualitative composition of the microbiota. Probiotic bacteria favorably modify the composition of the intestinal microbiota, inhibit the development of intestinal pathogens, prevent constipation, strengthen the immune system, and reduce symptoms of lactose intolerance. As fermented milk beverages are an excellent source of probiotic bacteria, their regular consumption can be a strong point in the prevention of various types of civilization diseases.

The presence of lactic acid bacteria, including probiotic bacteria in fermented milk beverages, reduces the incidence of obesity and diabetes and serves as a tool in the prevention of cancer diseases.

The present investigation explores into the influence of dietary nutrients, particularly alpha-linolenic acid (ALA), a plant-derived omega-3 fatty acid abundant in perilla seed oil (PSO), on the development of colitis-associated colorectal cancer (CRC). The study employs a mouse model to scrutinize the effects of ALA-rich PSO in the context of inflammation-driven CRC. Perilla seeds were subjected to oil extraction, and the nutritional composition of the obtained oil was analysed. Male ICR mice, initiated at four weeks of age, were subjected to diets comprising 5%, 10%, or 20% PSO, 10% fish oil, or 5% soybean oil. All groups, with the exception of the control group (5% soybean oil), underwent induction with azoxymethane (AOM) and dextran sulphate sodium (DSS) to instigate CRC. Disease development, colon samples, preneoplastic lesions, dysplasia, and biomarkers were meticulously evaluated. Furthermore, gut microbiota composition was elucidated through 16S rRNA sequencing. The analysis revealed that PSO contained 61.32% ALA and 783.90 mg/kg tocopherols. Mice subjected to diets comprising 5% soybean or 10% fish oil exhibited higher tumour incidence, burden, multiplicity, and aberrant crypt counts. Remarkably, these parameters were significantly reduced in mice fed a 5% PSO diet. Additionally, 5% PSO-fed mice displayed reduced proliferative and pro-inflammatory markers in colon tissues, coupled with an alleviation of AOM/DSS-induced gut dysbiosis. Notably, PSO demonstrated inhibitory effects on colitis-associated CRC in the AOM/DSS mice model, achieved through the suppression of proliferative and pro-inflammatory protein levels, and mitigation of gut dysbiosis, with discernible efficacy observed at a 5% dietary concentration.

The rapidly rising prevalence of metabolic diseases has turned them into an escalating global health concern. By producing or altering metabolic products, the gut microbiota plays a pivotal role in maintaining human health and influencing disease development. These metabolites originate from the host itself or the external environment. In the system of interactions between microbes and the host, tryptophan (Trp) plays a central role in metabolic processes. As the amino acid in the human body that must be obtained through dietary intake, it is crucial for various physiological functions. Trp can be metabolized in the gut into three main products: The gut microbiota regulates the transformation of 5-hydroxytryptamine (5-HT, serotonin), kynurenine (Kyn), and various indole derivatives. It has been revealed that a substantial correlation exists between alterations in Trp metabolism and the initiation and progression of metabolic disorders, including obesity, diabetes, non-alcoholic fatty liver disease, and atherosclerosis, but Trp metabolites have not been comprehensively reviewed in metabolic diseases. As such, this review summarizes and analyzes the latest research, emphasizing the importance of further studying Trp metabolism within the gut microbiota to understand and treat metabolic diseases. This carries potential significance for improving human health and may introduce new therapeutic strategies.

Helicobacter pylori infection is still the main risk factor for the development of gastric cancer (GC). We explore the scientific evidence for the role of the gastric microbiome beyond Helicobacter pylori (H. pylori) in gastric carcinogenesis. The composition of the gastric microbiome in healthy individuals, in presence and absence of H. pylori infection, in proton pump inhibitor (PPI)-users, obese individuals, and GC patients was investigated. Possible mechanisms for microbial involvement, limitations of available research and options for future studies are provided. A common finding amongst studies was increased levels of Streptococcus, Prevotella, Neisseria, and Actinomyces in healthy individuals or those with H. pylori-negative gastritis. In PPI-users the risk for GC increases with the treatment duration, and the gastric microbiome shifts, with the most consistent increase in the genus Streptococcus. Similarly, in obese individuals, Streptococcus was the most abundant genus, with an increased risk for cardia GC. The genera Streptococcus, Lactobacillus and Prevotella were found to be more prominent in GC patients in multiple studies. Potential mechanisms of non-H. pylori microbiota contributing to GC are linked to lipopolysaccharide production, contribution to inflammatory pathways, and the formation of N-nitroso compounds and reactive oxygen species. In conclusion, the knowledge of the gastric microbiome in GC is mainly descriptive and based on sequencing of gastric mucosal samples. For a better mechanistic understanding of microbes in GC development, longitudinal cohorts including precancerous lesions, different regions in the stomach, and subtypes of GC, and gastric organoid models for diffuse and intestinal type GC should be employed.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

The gut microbiome plays a crucial role in human health by influencing various physiological functions through complex interactions with the endocrine system. These interactions involve the production of metabolites, signaling molecules, and direct communication with endocrine cells, which modulate hormone secretion and activity. As a result, the microbiome can exert neuroendocrine effects and contribute to metabolic regulation, adiposity, and appetite control. Additionally, the gut microbiome influences reproductive health by altering levels of sex hormones such as estrogen and testosterone, potentially contributing to conditions like polycystic ovary syndrome (PCOS) and hypogonadism. Given these roles, targeting the gut microbiome offers researchers and clinicians novel opportunities to improve overall health and well-being. Probiotics, such as Lactobacillus and Bifidobacterium, are live beneficial microbes that help maintain gut health by balancing the microbiota. Prebiotics, non-digestible fibers, nourish these beneficial bacteria, promoting their growth and activity. When combined, probiotics and prebiotics form synbiotics, which work synergistically to enhance the gut microbiota balance and improve metabolic, immune, and hormonal health. This integrated approach shows promising potential for managing conditions related to hormonal imbalances, though further research is needed to fully understand their specific mechanisms and therapeutic potential.

Type 2 diabetes mellitus (T2DM) and progressive liver disease are 2 of the most significant global health concerns, and they have alarming and ever-increasing prevalence. A growing body of literature has demonstrated a potential multilateral link between gut microbiome dysbiosis and the development and progression of the above-mentioned conditions. Modulation of gut microbial composition from the norm is due to changes in diet allied with external factors such as age, genetics, and environmental changes. In this comprehensive review, we recapitulate the research to date investigating the links between gut microbiome dysbiosis and T2DM or liver disease, with special attention to the importance of diet. Additionally, we review the most commonly used tools and methodologies of investigating changes in the gut microbiome, highlighting the advantages and limitations of each strategy, before introducing a novel in vitro approach to the problem. Finally, the review offers recommendations for future research in this field that will allow better understanding of how the gut microbiota affects disease progression and of the prospects for intestinal microbiota-based therapeutic options.

The gut microbiota plays a role in energy homeostasis: its composition differs in lean and obese mice and may impact insulin sensitivity. The immune system has co-evolved with the gut microbiota, but direct regulation of microbial communities by the immune system and its metabolic impact is unclear. Mice lacking the immune cell specific transcription factor T-bet (Tbx21) are insulin sensitive. Compared with wild-type mice, T-bet deficient mice were found to have a higher proportion of colonic regulatory T cells despite significantly fewer colonic T cells, B cells and NK cells. Microbiota deletion by administration of antibiotics, increased colonic immune cell numbers. Furthermore, we report that T-bet -/- mice have an altered gut microbial composition and fecal short-chain fatty acid content, with an increase in butyrate production, compared with wild-type mice. Finally, in a proof-of concept study, we show that the enhanced insulin sensitivity observed in T-bet -/- mice is temporarily transmissible to antibiotic-treated wild-type mice through fecal transfer. Immune regulation of the gut microbiota by T-bet may be a novel pathway modulating insulin sensitivity.

Fructooligosaccharide (FOS) is a widely used prebiotic and health food ingredient, but few reports have focused on its risk to specific populations. Recently, it has been shown that the intake of inulin, whose main component is FOS, can lead to cholestasis and induce hepatocellular carcinoma in mice fed a high-fat diet (HFD); however, the molecular mechanism behind this is not clear. This study found that FOS supplementation induced abnormal enterohepatic circulation of bile acids in HFD-fed mice, which showed a significant increase in bile acid levels in the blood and liver, especially the secondary bile acids with high cytotoxicity, such as deoxycholic acid. The abundance of Clostridium, Bacteroides, and other bacteria in the gut microbiota also increased significantly. The analysis of the signaling pathway involved in regulating the enterohepatic circulation of bile acids showed that the weakening of the feedback inhibition of FXR-FGF15 and FXR-SHP signalling pathways possibly induced the enhancement of CYP7A1 activity and bile acid reabsorption in the blood and liver and led to an increase in bile acid synthesis and accumulation in the liver, increasing the risk of cholestasis. This study showed the risk of health damage caused by FOS supplementation in HFD-fed mice, which is caused by gut microbiota dysfunction and abnormal enterohepatic circulation of bile acids. Therefore, the application of FOS should be standardized to avoid the health risks of unreasonable FOS use in specific populations.

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.

Myocardial infarction (MI) remains the leading cause of death globally, imposing a significant burden on healthcare systems and patients. The gut-heart axis, a bidirectional network connecting gut health to cardiovascular outcomes, has recently emerged as a critical factor in MI pathophysiology. Disruptions in this axis, including gut dysbiosis and compromised intestinal barrier integrity, lead to systemic inflammation driven by gut-derived metabolites like lipopolysaccharides (LPSs) and trimethylamine N-oxide (TMAO), both of which exacerbate MI progression. In contrast, metabolites such as short-chain fatty acids (SCFAs) from a balanced microbiota exhibit protective effects against cardiac damage. This review examines the molecular mediators of the gut-heart axis, considering the role of factors like sex-specific hormones, aging, diet, physical activity, and alcohol consumption on gut health and MI outcomes. Additionally, we highlight therapeutic approaches, including dietary interventions, personalized probiotics, and exercise regimens. Addressing the gut-heart axis holds promise for reducing MI risk and improving recovery, positioning it as a novel target in cardiovascular therapy.

This study investigated the physicochemical properties, digestive stability, and in vitro fermentation behavior of Polygonatum kingianum polysaccharide (PKP) fractions (PKP60, PKP70, PKP80) obtained through graded ethanol precipitation. High-performance gel permeation chromatography revealed significant molecular weight differences among the fractions, while reverse-phase high-performance liquid chromatography indicated consistent monosaccharide types with variations in their proportions. Uronic acid analysis confirmed that all polysaccharide fractions met the criteria for neutral polysaccharides. Congo red staining confirmed the presence of a triple-helix structure in all PKP fractions. Comprehensive analysis demonstrated that these fractions remained stable during in vitro digestion, as evidenced by consistent molecular weights and total carbohydrate content, with no significant production of free monosaccharides or reducing sugars. All PKP fractions were fermented by gut microbiota, resulting in the production of short-chain fatty acids. Beta diversity and structural analyses of gut microbiota revealed distinct modulatory effects associated with each PKP fraction. The PKP fractions promoted probiotic growth, especially PKP70, which significantly enhanced Bifidobacterium proliferation, indicating strong prebiotic potential. These findings underscore the importance of isolation and purification methods in determining the functionality and gut microbiota-modulating effects of plant-derived polysaccharides, emphasizing the need for in-depth research that extends beyond merely evaluating their source.