In the diverse landscape of African hominids, the obligate relationship between the host and its microbiome narrates signals of adaptation and co-evolution. Sequencing 546 African hominid metagenomes, including those from indigenous Hadza and wild chimpanzees, identified similar bacterial richness and diversity surpassing those of westernized populations. While hominids share core bacterial communities, they also harbor distinct, population-specific bacterial taxa tailored to specific diets, ecology and lifestyles, differentiating non-indigenous and indigenous humans and chimpanzees. Even amongst shared bacterial communities, several core bacteria have co-diversified to fulfil unique dietary degradation functions within their host populations. These co-evolutionary trends extend to non-bacterial elements, such as mitochondrial DNA, antimicrobial resistance, and parasites. Our findings indicate that microbiome-host co-adaptations have led to both taxonomic and within taxa functional displacements to meet host physiological demands. The microbiome, in turn, transcends its taxonomic interchangeable role, reflecting the lifestyle, ecology and dietary history of its host.

The complex interactions between host genetics and the gut microbiome are well documented. However, the specific impacts of gene expression patterns and microbial composition on each other remain to be further explored.

Here, we investigated this complex interplay in a sizable population of 705 hens, employing integrative analyses to examine the relationships among the host genome, mucosal gene expression, and gut microbiota. Specific microbial taxa, such as the cecal family Christensenellaceae, which showed a heritability of 0.365, were strongly correlated with host genomic variants. We proposed a novel concept of regulatability ( r b 2 ), which was derived from h2, to quantify the cumulative effects of gene expression on the given phenotypes. The duodenal mucosal transcriptome emerged as a potent influencer of duodenal microbial taxa, with much higher r b 2 values (0.17 ± 0.01, mean ± SE) than h2 values (0.02 ± 0.00). A comparative analysis of chickens and humans revealed similar average microbiability values of genes (0.18 vs. 0.20) and significant differences in average r b 2 values of microbes (0.17 vs. 0.04). Besides, cis ( h cis 2 ) and trans heritability ( h trans 2 ) were estimated to assess the effects of genetic variations inside and outside the cis window of the gene on its expression. Higher h trans 2 values than h cis 2 values and a greater prevalence of trans-regulated genes than cis-regulated genes underscored the significant role of loci outside the cis window in shaping gene expression levels. Furthermore, our exploration of the regulatory effects of duodenal mucosal genes and the microbiota on 18 complex traits enhanced our understanding of the regulatory mechanisms, in which the CHST14 gene and its regulatory relationships with Lactobacillus salivarius jointly facilitated the deposition of abdominal fat by modulating the concentration of bile salt hydrolase, and further triglycerides, total cholesterol, and free fatty acids absorption and metabolism.

Our findings highlighted a novel concept of r b 2 to quantify the phenotypic variance attributed to gene expression and emphasize the superior role of intestinal mucosal gene expressions over host genomic variations in elucidating host‒microbe interactions for complex traits. This understanding could assist in devising strategies to modulate host-microbe interactions, ultimately improving economic traits in chickens.

Background/Objectives: Managing type 2 diabetes mellitus (T2DM) and obesity requires a multidimensional, patient-centered approach including nutritional interventions (NIs) and physical activity. Changes in the gut microbiota (GM) have been linked to obesity and the metabolic alterations typical of T2DM and obesity, and they are strongly influenced by diet. However, few studies have evaluated the effects on the GM of a very-low-calorie ketogenic diet (VLCKD) in patients with T2DM, especially in the mid-term and long-term. This longitudinal study is aimed at evaluating the mid-term and long-term impact of the VLCKD and Mediterranean diet (MD) on the GM and on the anthropometric, metabolic, and lifestyle parameters of 11 patients with T2DM and obesity (diabesity). This study extends previously published results evaluating the short-term (three months) impact of these NIs on the same patients. Methods: At baseline, patients were randomly assigned to either a VLCKD (KETO group) or a Mediterranean diet (MEDI group). After two months, the KETO group gradually shifted to a Mediterranean diet (VLCKD-MD), according to current VLCKD guidelines. From the fourth month until the end of the study both groups followed a similar MD. Previous published results showed that VLCKD had a more beneficial impact than MD on several variables for 3 months of NI. In this study, the analyses were extended until six (T6) and twelve months (T12) of NI by comparing data prospectively and against baseline (T0). The GM analysis was performed through next-generation sequencing. Results: Improvements in anthropometric and metabolic parameters were more pronounced in the KETO group at T6, particularly for body mass index (-5.8 vs. -1.7 kg/m2; p = 0.006) and waist circumference (-15.9 vs. -5.2 cm; p = 0.011). At T6, a significant improvement in HbA1c (6.7% vs. 5.5% p = 0.02) and triglyceride (158 vs. 95 mg/dL p = 0.04) values compared to T0 was observed only in the KETO group, which maintained the results achieved at T3. The VLCKD-MD had a more beneficial impact than the MD on the GM phenotype. A substantial positive modulatory effect was observed especially up to the sixth month of the NI in KETO due to the progressive increase in bacterial markers of human health. After the sixth month, most markers of human health decreased, though they were still increased compared with baseline. Among them, the Verrucomicrobiota phylum was identified as the main biomarker in the KETO group, together with its members Verrucomicrobiae, Akkermansiaceae, Verrucomicrobiales, and Akkermansia at T6 compared with baseline. Conclusions: Both dietary approaches ameliorated health status, but VLCKD, in support of the MD, has shown greater improvements on anthropometric and metabolic parameters, as well as on GM profile, especially up to T6 of NI.

The gut microbiota actually shares the host's physical space and affects the host's physiological functions and health indicators through a complex network of interactions with the host. However, its role as a determinant of host health and disease is often underestimated. With the emergence of new technologies including next-generation sequencing (NGS) and advanced techniques such as microbial community sequencing, people have begun to explore the interaction mechanisms between microorganisms and hosts at various omics levels such as genomics, transcriptomics, metabolomics, and proteomics. With the enrichment of multi-omics integrated analysis methods based on the microbiome, an increasing number of complex statistical analysis methods have also been proposed. In this review, we summarized the multi-omics research analysis methods currently used to study the interaction between the microbiome and the host. We analyzed the advantages and limitations of various methods and briefly introduced their application progress.

Microbiomes contribute to variation in many plant and animal traits, suggesting that microbiome-mediated traits could evolve through selection on the host. However, for such evolution to occur, microbiomes must exhibit sufficient heritability to contribute to host adaptation. Previous work has attempted to estimate the heritability of a variety of microbiome attributes. Here we show that most published estimates are limited to vertebrate and plant hosts, but significant heritability of microbiome attributes has been frequently reported. This indicates that microbiomes could evolve in response to host-level selection, but studies across a wider range of hosts are necessary before general conclusions can be made. We suggest future studies focus on standardizing heritability measurements for the purpose of meta-analyses and investigate the role of the environment in contributing to heritable microbiome variation. This could have important implications for the use of microbiomes in conservation, agriculture and medicine.

Women in Africa bear the burden of the HIV epidemic, which has been associated with the high prevalence of bacterial vaginosis (BV) in the region. However, little progress has been made in finding an effective cure for BV. Drawing on advances in microbiome-directed therapies for gastrointestinal disorders, similar live-biotherapeutic based approaches for BV treatment are being evaluated. Here, we summarize current knowledge regarding vaginal microbiota in BV, explore geographical differences in vaginal microbiota, and argue that novel BV therapeutics should be tailored specifically to meet the needs of African women.

Cervicovaginal microbiota dominated by Lactobacillus crispatus are optimal, although these are uncommon in African women. Besides socio-behavioural and environmental influences on the vaginal microbiota, host and microbial genetic traits should be considered, particularly those relating to glycogen metabolism. Novel microbiome-directed approaches being developed to treat BV should employ transfers of multiple microbial strains to ensure sustained colonization and BV cure.

Improving the efficacy and durability of BV treatment with microbiome-directed therapies by appropriately accounting for host and microbial genetic factors, could potentially reduce the risk of HIV infection in African women.

Obesity-induced insulin resistance (IR) can precipitate metabolic disorders such as diabetes. Zeaxanthin, a crucial member of the carotenoid family, has been found to mitigate the damage caused by obesity. However, reports on the effects of zeaxanthin on obesity-induced IR are lacking. Our objective was to examine the metabolic regulatory impacts of zeaxanthin on mice subjected to a high-fat diet (HFD) that triggered IR and to explore their influence on gut microbiota regulation. This study constructed a mouse model of metabolic dysfunction caused by lipid-rich nutritional patterns to investigate physiological and biochemical indices, liver pathway expression, and the intestinal microbiota. The mechanisms by which zeaxanthin improved both IR and glucose metabolic disorders were elucidated. The results demonstrate that zeaxanthin effectively suppressed obesity. The fasting blood glucose, area under curve of oral glucose tolerance test and insulin tolerance test, and homeostatic model assessment-insulin resistance (HOMA-IR) indices in the HFDZEA group decreased by 14.9%, 25.2%, 28.9%, and 29.8%. Additionally, zeaxanthin improved the lipid metabolism and alleviated damage to the liver and pancreas while also activating the PI3K/Akt pathway, regulating hepatic gluconeogenesis and the glycogen metabolism. The number of OTUs in the HFDZEA group increased by 29.04%. Zeaxanthin improved the structure and profile of the gastrointestinal microbiome and enhanced its diversity, increasing probiotics abundance, decreasing pathogen abundance, and thereby ameliorating the dysbiosis of enteric microbial communities in rodents with obesity resulting from excessive fat consumption. The outcomes of our analysis provide a rational basis for advancing zeaxanthin-based nutritional products.

Enteric pathogens, particularly bacterial pathogens, are associated with millions of cases of foodborne illness in the U.S. and worldwide, necessitating the identification and development of methods to control and minimize their impact on public health. Predictive modeling and quantitative microbial risk assessment are two such methods that analyze data on microbial behavior, particularly as a response to changes in the food matrix, to predict and control the presence and prevalence of these pathogens in food. However, a number of these bacterial enteric pathogens, including Escherichia coli, Listeria monocytogenes, and Salmonella enterica, have inherent genetic and phenotypic differences among their subtypes and variants. This has led to an increasing reliance on "omics" technologies, including genomics, proteomics, transcriptomics, and metabolomics, to identify and characterize pathogenic microorganisms and their behavior in food systems. With this exponential increase in available data on these enteric pathogens, comes a need for the development of novel strategies to analyze this data. Advanced data analysis/analytics is a means to extract value from these large data sources, and is considered the core of data processing. In the past few years, advanced data analytics methods such as machine learning and artificial intelligence have been increasingly used to extract meaningful, actionable knowledge from these data sources to help mitigate food safety issues caused by enteric pathogens. This chapter reviews the latest in research into the use of advanced data analytics, particularly machine learning, to analyze "omics" data of enteric bacterial pathogens, and identifies potential future uses of these techniques in mitigating the risk of these pathogens on public health.

Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs, which is associated with diverse metabolic abnormalities. We hypothesized that elevated cortisol levels in dogs with HAC disrupt the gut microbiome (GM), and this disruption persists even after trilostane treatment. This study explored GM composition in dogs with HAC. We included 24 dogs, 15 with HAC and 9 healthy controls, and followed up with 5 dogs with HAC who received trilostane treatment. The GM analysis revealed significant compositional changes in dogs with HAC, including reduced microbiome diversity compared to healthy controls, particularly in rare taxa, as indicated by the Shannon index (p = 0.0148). Beta diversity analysis further showed a distinct clustering of microbiomes in dogs with HAC, separating them from healthy dogs (p < 0.003). Specifically, an overrepresentation of Proteobacteria (Pseudomonadota), Actinobacteria, Bacteroides, Enterococcus, Corynebacterium, Escherichia, and Proteus populations occurred alongside a decreased Firmicutes (Bacillota) population. Despite trilostane treatment, gut dysbiosis persisted in dogs with HAC at a median of 41 d post treatment, suggesting its potential role in ongoing metabolic issues. We identified GM dysbiosis in dogs with HAC by examining key bacterial genera, offering insights into potential interventions like probiotics or fecal microbiota transplants for better HAC management.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems, often resulting in infertility, obesity, insulin resistance, and cardiovascular complications. The aim of this study is to investigate the role of intestinal flora and its metabolites, particularly short-chain fatty acids (SCFAs), in the development of PCOS, and to assess the effects of metformin therapy on these components. SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. Fecal microbiota were quantitatively detected by real-time polymerase chain reaction (PCR). To assess the efficacy of six months of metformin treatment, changes in the microbiota and SCFAs in the PCOS group (n=69) were also evaluated. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria (namely, the C. leptum group and Prevotella spp.) alongside a notable overgrowth of opportunistic microorganisms (C. perfringens, C. difficile, Staphylococcus spp., and Streptococcus spp.). An overproduction of acetic acid (AA, FC=0.47, p<0.05) and valeric acid (VA, FC=0.54, p<0.05) suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (r=-0.33, p=0.02), insulin resistance (r=-0.39, p=0.02), and chronic inflammation. Although serum SCFA levels showed non-significant changes following metformin treatment (p>0.05), the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food.

Hypertension is accompanied by gut microbiota imbalance, but the role of bacteria in the pathogenesis of hypertension requires further study. In this study, we used fecal microbiota transplantation to determine the impact of microbiota composition on blood pressure in spontaneous hypertensive rats (SHRs), using normotensive Wistar Kyoto (WKY) rats as controls. SHRs were randomly divided into two groups (n = 10/group), SHR and SHR-T (SHR plus fecal transplantation) and WKY into WKY and WKY-T (WKY plus fecal transplantation). SHR-T received fecal transplantation from WKY, while WKY-T received fecal transplantation from SHR. Blood pressure was measured from the tail artery in conscious rats. 16S rDNA gene amplicon sequencing was used to analyze bacterial composition. Circulating levels of diamine oxidase, D-lactate, FITC-Dextrans, and lipopolysaccharide were determined. Hematoxylin and eosin (H&E) staining was used to observe structural changes in the intestinal mucosa. Immunofluorescence, Western blot, and RT-PCR were utilized to determine changes in the expression of tight junction proteins. Following cross fecal transplantation, blood pressure decreased in SHR and increased in WKY. Significant differences in gut microbial composition were found between hypertensive and normotensive rats, specifically regarding the relative abundance of lactic and butyric acid-producing bacteria. Changes in gut microbiota composition also impacted the intestinal mucosal barrier integrity. Moreover, fecal transplantation affected the expression of tight junction proteins that may impact intestinal mucosal permeability and structural integrity. Blood pressure may be associated with butyric acid-producing intestinal microbiota and its function in regulating the integrity of intestinal mucosal barrier.

The gut microbiota (GM) can regulate bone mass, but its association with incident fractures is unknown. We used Cox regression models to determine whether the GM composition is associated with incident fractures in the large FINRISK 2002 cohort (n = 7043, 1092 incident fracture cases, median follow-up time 18 years) with information on GM composition and functionality from shotgun metagenome sequencing. Higher alpha diversity was associated with decreased fracture risk (hazard ratio [HR] 0.92 per standard deviation increase in Shannon index, 95% confidence interval 0.87-0.96). For beta diversity, the first principal component was associated with fracture risk (Aitchison distance, HR 0.90, 0.85-0.96). In predefined phyla analyses, we observed that the relative abundance of Proteobacteria was associated with increased fracture risk (HR 1.14, 1.07-1.20), while the relative abundance of Tenericutes was associated with decreased fracture risk (HR 0.90, 0.85-0.96). Explorative sub-analyses within the Proteobacteria phylum showed that higher relative abundance of Gammaproteobacteria was associated with increased fracture risk. Functionality analyses showed that pathways related to amino acid metabolism and lipopolysaccharide biosynthesis associated with fracture risk. The relative abundance of Proteobacteria correlated with pathways for amino acid metabolism, while the relative abundance of Tenericutes correlated with pathways for butyrate synthesis. In conclusion, the overall GM composition was associated with incident fractures. The relative abundance of Proteobacteria, especially Gammaproteobacteria, was associated with increased fracture risk, while the relative abundance of Tenericutes was associated with decreased fracture risk. Functionality analyses demonstrated that pathways known to regulate bone health may underlie these associations.

There is a significant focus on the role of the host microbiome in different outcomes of human parasitic diseases, including cystic echinococcosis (CE). This study was conducted to identify the intestinal microbiome of patients with CE at different stages of hydatid cyst compared to healthy individuals. Stool samples from CE patients as well as healthy individuals were collected. The samples were divided into three groups representing various stages of hepatic hydatid cyst: active (CE1 and CE2), transitional (CE3), and inactive (CE4 and CE5). One family member from each group was selected to serve as a control. The gut microbiome of patients with different stages of hydatid cysts was investigated using metagenomic next-generation amplicon sequencing of the V3-V4 region of the 16S rRNA gene. In this study, we identified 4862 Operational Taxonomic Units from three stages of hydatid cysts in CE patients and healthy individuals with a combined frequency of 2,955,291. The most abundant genera observed in all the subjects were Blautia, Agathobacter, Faecalibacterium, Bacteroides, Bifidobacterium, and Prevotella. The highest microbial frequency was related to inactive forms of CE, and the lowest frequency was observed in the group with active forms. However, the lowest OTU diversity was found in patients with inactive cysts compared with those with active and transitional cyst stages. The genus Agatobacter had the highest OTU frequency. Pseudomonas, Gemella, and Ligilactobacillus showed significant differences among the patients with different stages of hydatid cysts. Additionally, Anaerostipes and Candidatus showed significantly different reads in CE patients compared to healthy individuals. Our findings indicate that several bacterial genera can play a role in the fate of hydatid cysts in patients at different stages of the disease.

This study aimed to determine the effects of different doses of Acremonium terricola culture (ATC) on lactation performance, immune function, antioxidant capacity, and intestinal flora of sows. Forty-five Landrace sows (3-6 parity) were randomly assigned to the following three treatments from 85 days of gestation to 21 days after farrowing: a control diet (CON, basal diet), a low-dose Acremonium terricola culture diet (0.2% ATC, basal diet + 0.2% ATC), and a high-dose Acremonium terricola culture diet (0.4% ATC, basal diet + 0.4% ATC). Compared with the CON group, the supplementation of 0.2% ATC increased the average daily milk yield of sows by 4.98%, increased milk fat, total solids, and freezing point depression on day 1 postpartum (p < 0.05), increased serum concentration of Triiodothyronine, Thyroxin, and Estradiol on day 21 postpartum (p < 0.05). Compared with the CON group, the supplementation of 0.4% ATC increased the average daily milk yield of sows by 9.38% (p < 0.05). Furthermore, the supplementation of 0.2% ATC increased serum concentration of IgG, IgM, and IFN-γ, CD4 on day 1 postpartum (p < 0.05) and increased serum concentration of immunoglobulin A ( IgA), immunoglobulin G (IgG), immunoglobulin M ( IgM), complement 3 (C3), cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), interferon-γ (IFN-γ) on day 21 postpartum (p < 0.05), while the supplementation of 0.4% ATC reduced serum concentration of IL-2 on day 21 postpartum (p < 0.05). Moreover, the supplementation of 0.4% ATC significantly increased serum concentration of catalase (CAT) (p < 0.05). Additionally, the supplementation of ATC affected the relative abundance of the intestinal flora at different taxonomic levels in sows and increased the abundance of beneficial bacteria such as in the norank_f__Eubacterium_coprostanoligenes group, Eubacterium_coprostanoligenes group, and Lachnospiraceae_XPB1014 group of sows, while reducing the abundance of harmful bacteria such as Phascolarctobacterium and Clostridium_sensu_stricto_1. These data revealed that the supplementation of ATC during late gestation and lactation can improve lactation performance, immune function, antioxidant capacity, and the gut microbiota. Compared with supplementation of 0.4% ATC, 0.2% ATC enhances the levels of thyroid-related hormones, specific antibodies, and cytokines in serum, promotes the diversity of beneficial gut microbiota, beneficial bacteria in the intestine, reduces the population of harmful bacteria, and thereby bolsters the immunity of sows. Hence, 0.2% ATC is deemed a more optimal concentration.

In a recent study examining the effects of manipulating the gut microbiome on bone, a control group of mice in which the microbiome was altered using a non-caloric, aspartame-based sweetener resulted in whole bone strength being 40% greater than expected from geometry alone, implicating enhanced bone tissue strength. However, the study was not designed to detect changes in bone in this control group and was limited to young male mice. Here we report a replication study examining how changes in the gut microbiome caused by aspartame-based sweetener influence bone. Male and female C57Bl/6 J mice were untreated or treated with a high dose of sweetener (10 g/L) in their drinking water from either 1 to 4 mo of age (young cohort; n = 80) or 1 to 22 mo of age (aged cohort; n = 52). Sweetener did not replicate the modifications to the gut microbiome observed in the initial study and did not result in an increase in bone tissue strength in either sex at either age. Aged male mice dosed with sweetener had larger bones (+17% femur section modulus, p<.001) and greater whole bone strength (+22%, p=.006) but the increased whole bone strength was explained by the associated increase in body mass (+9%, p<.001). No differences in body mass, whole bone strength, or femoral geometry were associated with sweetener dosing in males from the young cohort or females at either age. As we were unable to replicate the gut microbiota observed in the initial experiment, it remains unclear if changes in the gut microbiome can enhance bone tissue strength. Although prior work studying gut microbiome-induced changes in bone with oral antibiotics has been highly repeatable, the current study highlights the variability of nutritional manipulations of the gut microbiota in mice.

The human microbiome functions as a separate organ in a symbiotic relationship with the host. Disruption of this host-microbe symbiosis can lead to serious health problems. Modifications to the composition and function of the microbiome have been linked to changes in host metabolic outcomes. Industrial lifestyles with high consumption of processed foods, alcoholic beverages and antibiotic use have significantly altered the gut microbiome in unfavorable ways. Therefore, understanding the causal relationship between the human microbiome and host metabolism will provide important insights into how we can better intervene in metabolic health. In this review, I will discuss the potential use of the human microbiome as a therapeutic target to improve host metabolism.

To investigate the impact of gut microbiota on osteoporosis and identify the mediating role of blood metabolites in this process.

This two-sample Mendelian randomization (MR) study utilized summary level data from genome-wide association studies (GWAS). Gut microbiota GWAS data were obtained from the MiBio-Gen consortium meta-analysis (n=13,266), while osteoporosis summary statistics were sourced from the FinnGen consortium R9 release data (7300 cases and 358,014 controls). Metabolite data, including 1400 metabolites or metabolite ratios, were derived from a study involving 8,299 unrelated individuals. The primary MR method employed was the inverse variance weighted (IVW) method. Reverse MR analysis was conducted on bacteria causally associated with osteoporosis in forward MR. The gut microbiota with the smallest p-value was selected as the top influencing factor for subsequent mediation analysis. A two-step MR approach quantified the proportion of the blood metabolite effect on gut microbiota influencing osteoporosis. IVW and Egger methods were used to assess heterogeneity and horizontal pleiotropy.

IVW estimates indicated a suggestive effect of family Christensenellaceae on osteoporosis (odds ratio(OR) = 1.292, 95% confidence interval(CI): 1.110-1.503, P =9.198 × 10-4). Reverse MR analysis revealed no significant causal effect of osteoporosis on family Christensenellaceae (OR = 0.947, 95% CI: 0.836-1.072, P =0.386). The proportion of the effect of family Christensenellaceae on osteoporosis mediated by circulating levels of 3,4-dihydroxybutyrate was 9.727%. No significant heterogeneity or horizontal pleiotropy was detected in the instrumental variables used for MR analysis.

This study establishes a causal link between family Christensenellaceae and osteoporosis, with a minor proportion of the effect mediated by elevated circulating levels of 3,4-dihydroxybutyrate. Further randomized controlled trials (RCTs) are warranted to validate this conclusion.

Obesity has been demonstrated as a risk factor that seriously affects health. Insoluble dietary fiber (IDF), as a major component of dietary fiber, has positive effects on obesity, inflammation and diabetes.

In this study, complex IDF was prepared using 50% enoki mushroom IDF, 40% carrot IDF, and 10% oat IDF. The effects and potential mechanism of complex IDF on obesity were investigated in C57BL/6 mice fed a high-fat diet. The results showed that feeding diets containing 5% complex IDF for 8 weeks significantly reduced mouse body weight, epididymal lipid index, and ectopic fat deposition, and improved mouse liver lipotoxicity (reduced serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), fatty liver, and short-chain fatty acid composition. High-throughput sequencing of 16S rRNA and analysis of fecal metabolomics showed that the intervention with complex IDF reversed the high-fat-diet-induced dysbiosis of gut microbiota, which is associated with obesity and intestinal inflammation, and affected metabolic pathways, such as primary bile acid biosynthesis, related to fat digestion and absorption.

Composite IDF intervention can effectively inhibit high-fat-diet-induced obesity and related symptoms and affect the gut microbiota and related metabolic pathways in obesity. Complex IDF has potential value in the prevention of obesity and metabolic syndrome. © 2024 Society of Chemical Industry.

The composition of the human gut microbiome varies tremendously among individuals, making the effects of dietary or treatment interventions difficult to detect and characterize. The consumption of fiber is important for gut health, yet the specific effects of increased fiber intake on the gut microbiome vary across studies. The variation in study outcomes might be due to inter-individual (or inter-population) variation or to the details of the interventions including the types of fiber, length of study, size of cohort, and molecular approaches. Thus, to identify generally (on average) consistent fiber-induced responses in the gut microbiome of healthy individuals, we re-analyzed 16S rRNA sequencing data from 21 dietary fiber interventions from 12 human studies, which included 2,564 fecal samples from 538 subjects across all interventions. Short-term increases in dietary fiber consumption resulted in highly consistent gut bacterial community responses across studies. Increased fiber consumption explained an average of 1.5% of compositional variation (vs 82% of variation attributed to the individual), reduced alpha-diversity, and resulted in phylogenetically conserved responses in relative abundances among bacterial taxa. Additionally, we identified bacterial clades, at approximately the genus level, that were highly consistent in their response (on average, increasing or decreasing in their relative abundance) to dietary fiber interventions across the studies.

Our study is an example of the power of synthesizing and reanalyzing 16S rRNA microbiome data from many intervention studies. Despite high inter-individual variation of the composition of the human gut microbiome, dietary fiber interventions cause a consistent response both in the degree of change and the particular taxa that respond to increased fiber.

The association between Apolipoprotein A5 (APOA5) genetic polymorphisms and susceptibility to metabolic syndrome (MetS) has been established by many studies, but there have been conflicting results from the literature. We performed a meta-analysis of observational studies to evaluate the association between APOA5 gene polymorphisms and the prevalence of MetS.

PubMed, Web of Science, Embase, and Scopus were searched up to April 2024. The random effects model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CI) of the association between APOA5 gene polymorphisms and the prevalence of MetS development. The potential sources of heterogeneity were evaluated by subgroup analyses and sensitivity analyses.

A total of 30 studies with 54,986 subjects (25,341 MetS cases and 29,645 healthy controls) were included. The presence of rs662799 and rs651821 polymorphisms is associated with an approximately 1.5-fold higher likelihood of MetS prevalence (OR = 1.42, 95% CI: 1.32, 1.53, p < 0.001; I2 = 67.1%; P-heterogeneity < 0.001; and OR = 1.50, 95% CI: 1.36-1.65, p < 0.001), respectively. MetS is also more prevalent in individuals with the genetic variants rs3135506 and rs2075291. There was no evidence of a connection with rs126317.

The present findings suggest that polymorphisms located in the promoter and coding regions of the APOA5 gene are associated with an increased prevalence of MetS in the adult population. Identifying individuals with these genetic variations could lead to early disease detection and the implementation of preventive strategies to reduce the risk of MetS and its related health issues. However, because the sample size was small and there was evidence of significant heterogeneity for some APOA5 gene polymorphisms, these results need to be confirmed by more large-scale and well-designed studies.

Cardio-metabolic disease is a significant global health challenge with increasing prevalence. Recent research underscores the disruption of gut microbial balance as a key factor in disease susceptibility. We aimed to characterize the gut microbiota composition and function in cardio-metabolic disease and healthy controls. For this purpose, we collected stool samples of 18 subjects (12 diseased, 6 healthy) and we performed metagenomics analysis and functional prediction using QIIME2 and PICRUSt. Furthermore, we carried out assessments of microbe-gene interactions, gene ontology, and microbe-disease associations. Our findings revealed distinct microbial patterns in the diseased group, particularly evident in lower taxonomic levels with significant variations in 14 microbial features. The diseased cohort exhibited an enrichment of Lachnospiraceae family, correlating with obesity, insulin resistance, and metabolic disturbances. Conversely, reduced levels of Clostridium, Gemmiger, and Ruminococcus genera indicated a potential inflammatory state, linked to compromised butyrate production and gut permeability. Functional analyses highlighted dysregulated pathways in amino acid metabolism and energy equilibrium, with perturbations correlating with elevated branch-chain amino acid levels-a known contributor to insulin resistance and type 2 diabetes. These findings were consistent across biomarker assessments, microbe-gene associations, and gene ontology analyses, emphasizing the intricate interplay between gut microbial dysbiosis and cardio-metabolic disease progression. In conclusion, our study unveils significant shifts in gut microbial composition and function in cardio-metabolic disease, emphasizing the broader implications of microbial dysregulation. Addressing gut microbial balance emerges as a crucial therapeutic target in managing cardio-metabolic disease burden.

How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions?

Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs.

Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs.

This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included.

A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method.

We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03).

Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population.

The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs.

This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare.

N/A.

Observational studies have reported that gut microbiota composition is associated with metabolic syndrome. However, the causal effect of gut microbiota on metabolic syndrome has yet to be confirmed.

We performed a bidirectional Mendelian randomization study to investigate the causal effect between gut microbiota and metabolic syndrome in European population. Summary statistics of gut microbiota were from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium. The summary statistics of outcome were obtained from the most comprehensive genome-wide association studies of metabolic syndrome (n = 291,107). The inverse-variance weighted method was applied as the primary method, and the robustness of the results was assessed by a series of sensitivity analyses.

In the primary causal estimates, Actinobacteria (OR = 0.935, 95% CI = 0.878-0.996, P = 0.037), Bifidobacteriales (OR = 0.928, 95% CI = 0.868-0.992, P = 0.028), Bifidobacteriaceae (OR = 0.928, 95% CI = 0.868-0.992, P = 0.028), Desulfovibrio (OR = 0.920, 95% CI = 0.869-0.975, P = 0.005), and RuminococcaceaeUCG010 (OR = 0.882, 95% CI = 0.803-0.969, P = 0.009) may be associated with a lower risk of metabolic syndrome, while Lachnospiraceae (OR = 1.130, 95% CI = 1.016-1.257, P = 0.025), Veillonellaceae (OR = 1.055, 95% CI = 1.004-1.108, P = 0.034) and Olsenella (OR = 1.046, 95% CI = 1.009-1.085, P = 0.015) may be linked to a higher risk for metabolic syndrome. Reverse MR analysis demonstrated that abundance of RuminococcaceaeUCG010 (OR = 0.938, 95% CI = 0.886-0.994, P = 0.030) may be downregulated by metabolic syndrome. Sensitivity analyses indicated no heterogeneity or horizontal pleiotropy.

Our Mendelian randomization study provided causal relationship between specific gut microbiota and metabolic syndrome, which might provide new insights into the potential pathogenic mechanisms of gut microbiota in metabolic syndrome and the assignment of effective therapeutic strategies.

The purpose of this review is to investigate the relationship between gastrointestinal microbiome, obesity, and gestational diabetes mellitus (GDM) in an objective manner.

We conducted a thorough and comprehensive search of the English language literatures published in PubMed, Web of Science, and the Cochrane Library from the establishment of the library until 12 December 2023. Our search strategy included both keywords and free words searches, and we strictly applied inclusion and exclusion criteria. Meta-analyses and systematic reviews were prepared.

Six high-quality literature sources were identified for meta-analysis. However, after detailed study and analysis, a certain degree of heterogeneity was found, and the credibility of the combined analysis results was limited. Therefore, descriptive analyses were conducted. The dysbiosis of intestinal microbiome, specifically the ratio of Firmicutes/Bacteroides, is a significant factor in the development of metabolic diseases such as obesity and gestational diabetes. Patients with intestinal dysbiosis and obesity are at a higher risk of developing GDM.

During pregnancy, gastrointestinal microbiome disorders and obesity may contribute to the development of GDM, with all three factors influencing each other. This finding could aid in the diagnosis and management of patients with GDM through further research on their gastrointestinal microbiome.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing.

Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2). FL1 and FL2 patients were divided into two groups, those with either hyperlipidemia or non-hyperlipidemia based on their blood lipids. Potential keystone species within the groups were identified using univariate analysis and a specificity-occupancy plot. Significant difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence analysis.

Decreased gut bacterial diversity was found in patients with NAFLD. Firmicutes/Bacteroidetes decreased as NAFLD progressed. Faecalibacterium and Ruminococcus 2 were the most representative fatty-related bacteria. Glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count were selected as the most significant biochemical indexes. Calculation of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing FL1.

Faecalibacterium and Ruminococcus 2, combined with glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count distinguished NAFLD. We speculate that regulating the health of gut microbiota may release NAFLD, in addition to providing new targets for clinicians to treat NAFLD.

Consumption of dietary fiber has been suggested as an important aspect of a healthy diet to reduce the risk of metabolic syndrome (MetS), including cardiovascular disease. The role of fiber intake in MetS might differ by individual genetic susceptibility. APOA5 encodes a regulator of plasma triglyceride levels, which impacts the related mechanisms of MetS. This study investigated the association between dietary fiber and the risk of MetS, assessing their associations according to APOA5 genetic variants.

A total of 1985 participants aged 30-55 years were included from a cross-sectional study based on the Korean Medicine Daejeon Citizen Cohort study at baseline (2017-2019). Dietary fiber intake was measured using a semiquantitative food frequency questionnaire. The APOA5 polymorphisms (rs2266788 A > G, rs662799 A > G, and rs651821 T > C) were genotyped using the Asia Precision Medicine Research Array. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs).

A higher consumption of dietary fiber was associated with a lower prevalence of MetS (P = 0.025). Among the components of MetS, an inverse association with dietary fiber was observed in increased waist circumference (OR, 95% CI = 0.60, 0.41-0.88, P for trend = 0.009) and elevated triglycerides (OR, 95% CI = 0.69, 0.50-0.96, P for trend = 0.012). Regarding the interaction with APOA5 genetic variants, a stronger association with dietary fiber intake was shown in G allele carriers of rs662799 than in A/A carriers (OR, 95% CI = 2.34, 1.59-3.44, P for interaction = 0.024) and in C allele carriers of rs651821 than in T/T carriers (OR, 95% CI = 2.35, 1.59-3.46, P for interaction = 0.027).

The findings of this study suggest that the benefits of dietary fiber on the risk of MetS could be modified by genetic variants of the APOA5 gene, providing a more effective strategy for preventing MetS.

The occurrence of metabolic syndrome (MetS) and the gut microbiota composition are known to differ across ethnicities yet how these three factors are interwoven is unknown. Also, it is unknown what the relative contribution of the gut microbiota composition is to each MetS component and whether this differs between ethnicities. We therefore determined the occurrence of MetS and its components in the multi-ethnic HELIUS cohort and tested the overall and ethnic-specific associations with the gut microbiota composition.

We included 16,209 treatment naïve participants of the HELIUS study, which were of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish, and Moroccan descent to analyze MetS and its components across ethnicities. In a subset (n = 3443), the gut microbiota composition (16S) was associated with MetS outcomes using linear and logistic regression models.

A differential, often sex-dependent, prevalence of MetS components and their combinations were observed across ethnicities. Increased blood pressure was commonly seen especially in Ghanaians, while South-Asian Surinamese and Turkish had higher MetS rates in general and were characterized by worse lipid-related measures. Regarding the gut microbiota, when ethnic-independent associations were assumed, a higher α-diversity, higher abundance of several ASVs (mostly for waist and triglyceride-related outcomes) and a trophic network of ASVs of Ruminococcaceae, Christensenellaceae, and Methanobrevibacter (RCM) bacteria were associated with better MetS outcomes. Statistically significant ethnic-specific associations were however noticed for α-diversity and the RCM trophic network. Associations were significant in the Dutch but not always in all other ethnicities. In Ghanaians, a higher α-diversity and RCM network abundance showed an aberrant positive association with high blood pressure measures compared to the other ethnicities. Even though adjustment for socioeconomic status-, lifestyle-, and diet-related variables often attenuated the effect size and/or the statistical significance of the ethnic-specific associations, an overall similar pattern across outcomes and ethnicities remained.

The occurrence of MetS characteristics among ethnicities is heterogeneous. Both ethnic-independent and ethnic-specific associations were identified between the gut microbiota and MetS outcomes. Across multiple ethnicities, a one-size-fits-all approach may thus be reconsidered in regard to both the definition and/or treatment of MetS and its relation to the gut microbiota.

Social isolation, a known stressor, can have detrimental effects on both physical and mental health. Recent scientific attention has been drawn to the gut-brain axis, a bidirectional communication system between the central nervous system and gut microbiota, suggesting that gut microbes may influence brain function. This study aimed to explore the impact of social isolation on the intestinal barrier and gut microbiota. 40 male BALB/c mice were either individually housed or kept in groups for 8 and 15 weeks. Socially isolated mice exhibited increased anxiety-like behavior, with significant differences between the 8-week and 15-week isolation groups (P < 0.05). After 8 weeks of isolation, there was a reduction in tight junction protein expression in the intestinal mechanical barrier. Furthermore, after 15 weeks of isolation, both tight junction protein and mucin expression, key components of the intestinal chemical barrier, decreased. This was accompanied by a substantial increase in inflammatory cytokines (IL-6 mRNA, IL-10, and TNF-α) in colon tissue in the 15-week isolated group (P < 0.05). Additionally, Illumina MiSequencing revealed significant alterations in the gut microbiota of socially isolated mice, including reduced Firmicutes and Bacteroides compared to the control group. Lactobacillus levels also decreased in the socially isolated mice.

The gut microbiota is emerging as an important contributor to the homeostasis of the human body through its involvement in nutrition and metabolism, protection against pathogens, and the development and modulation of the immune system. It has therefore become an important research topic in recent decades. Although the association between intestinal dysbiosis and numerous digestive pathologies has been thoroughly researched, its involvement in pancreatic diseases constitutes a novelty in the specialized literature. In recent years, growing evidence has pointed to the critical involvement of the pancreas in regulating the intestinal microbiota, as well as the impact of the intestinal microbiota on pancreatic physiology, which implies the existence of a bidirectional connection known as the "gut-pancreas axis". It is theorized that any change at either of these levels triggers a response in the other component, hence leading to the evolution of pancreatitis. However, there are not enough data to determine whether gut dysbiosis is an underlying cause or a result of pancreatitis; therefore, more research is needed in this area. The purpose of this narrative review is to highlight the role of gut dysbiosis in the pathogenesis of acute and chronic pancreatitis, its evolution, and the prospect of employing the microbiota as a therapeutic intervention for pancreatitis.

While polyphenol consumption is often associated with an increased abundance of beneficial microbes and decreased opportunistic pathogens, these relationships are not completely described for polyphenols consumed via habitual diet, including culinary herb and spice consumption. This analysis of the International Cohort on Lifestyle Determinants of Health (INCLD Health) cohort uses a dietary questionnaire and 16s microbiome data to examine relationships between habitual polyphenol consumption and gut microbiota in healthy adults (n = 96). In this exploratory analysis, microbial taxa, but not diversity measures, differed by levels of dietary polyphenol consumption. Taxa identified as exploratory biomarkers of daily polyphenol consumption (mg/day) included Lactobacillus, Bacteroides, Enterococcus, Eubacterium ventriosum group, Ruminococcus torques group, and Sutterella. Taxa identified as exploratory biomarkers of the frequency of polyphenol-weighted herb and spice use included Lachnospiraceae UCG-001, Lachnospiraceae UCG-004, Methanobrevibacter, Lachnoclostridium, and Lachnotalea. Several of the differentiating taxa carry out activities important for human health, although out of these taxa, those with previously described pro-inflammatory qualities in certain contexts displayed inverse relationships with polyphenol consumption. Our results suggest that higher quantities of habitual polyphenol consumption may support an intestinal environment where opportunistic and pro-inflammatory bacteria are represented in a lower relative abundance compared to those with less potentially virulent qualities.

The gut bacteria of the family Christensenellaceae are consistently associated with metabolic health, but their role in promoting host health is not fully understood. Here, we explored the effect of Christensenella minuta amendment on voluntary physical activity and the gut microbiome. We inoculated male and female germ-free mice with an obese human donor microbiota together with live or heat-killed C. minuta for 28 days and measured physical activity in respirometry cages. Compared to heat-killed, the live-C. minuta treatment resulted in reduced feed efficiency and higher levels of physical activity, with significantly greater distance traveled for males and higher levels of small movements and resting metabolic rate in females. Sex-specific effects of C. minuta treatment may be in part attributable to different housing conditions for males and females. Amendment with live C. minuta boosted gut microbial biomass in both sexes, immobilizing dietary carbon in the microbiome, and mice with high levels of C. minuta lose more energy in stool. Live C. minuta also reduced within and between-host gut microbial diversity. Overall, our results showed that C. minuta acts as a keystone species: despite low relative abundance, it has a large impact on its ecosystem, from the microbiome to host energy homeostasis.IMPORTANCEThe composition of the human gut microbiome is associated with human health. Within the human gut microbiome, the relative abundance of the bacterial family Christensenellaceae has been shown to correlate with metabolic health and a lean body type. The mechanisms underpinning this effect remain unclear. Here, we show that live C. minuta influences host physical activity and metabolic energy expenditure, accompanied by changes in murine metabolism and the gut microbial community in a sex-dependent manner in comparison to heat-killed C. minuta. Importantly, live C. minuta boosts the biomass of the microbiome in the gut, and a higher level of C. minuta is associated with greater loss of energy in stool. These observations indicate that modulation of activity levels and changes to the microbiome are ways in which the Christensenellaceae can influence host energy homeostasis and health.

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.

As the field of probiotic research continues to expand, new beneficial strains are being discovered. The Christensenellaceae family and its newly described member, Christensenella minuta, have been shown to offer great health benefits. We aimed to extensively review the existing literature on these microorganisms to highlight the advantages of their use as probiotics and address some of the most challenging aspects of their commercial production and potential solutions.

We applied a simple search algorithm using the key words "Christensenellaceae" and "Christensenella minuta" to find all articles reporting the biotherapeutic effects of these microorganisms. Only articles reporting evidence-based results were reviewed.

The review showed that Christensenella minuta has demonstrated numerous beneficial properties and a wider range of uses than previously thought. Moreover, it has been shown to be oxygen-tolerant, which is an immense advantage in the manufacturing and production of Christensenella minuta-based biotherapeutics. The results suggest that Christensenellaceae and Christensenella munita specifically can play a crucial role in maintaining a healthy gut microbiome. Furthermore, Christensenellaceae have been associated with weight management. Preliminary studies suggest that this probiotic strain could have a positive impact on metabolic disorders like diabetes and obesity, as well as inflammatory bowel disease.

Christensenellaceae and Christensenella munita specifically offer immense health benefits and could be used in the management and therapy of a wide range of health conditions. In addition to the impressive biotherapeutic effect, Christensenella munita is oxygen-tolerant, which facilitates commercial production and storage.

There is a lot of evidence establishing that nervous system development is related to the composition and functions of the gut microbiome. In addition, the central nervous system (CNS) controls the imbalance of the intestinal microbiota, constituting a bidirectional communication system. At present, various gut-brain crosstalk routes have been described, including immune, endocrine and neural circuits via the vagal pathway. Several empirical data have associated gut microbiota alterations (dysbiosis) with neuropsychiatric diseases, such as Alzheimer's disease, autism and Parkinson's disease, and with other psychological disorders, like anxiety and depression. Fecal microbiota transplantation (FMT) therapy has shown that the gut microbiota can transfer behavioral features to recipient animals, which provides strong evidence to establish a causal-effect relationship. Interventions, based on prebiotics, probiotics or synbiotics, have demonstrated an important influence of microbiota on neurological disorders by the synthesis of neuroactive compounds that interact with the nervous system and by the regulation of inflammatory and endocrine processes. Further research is needed to demonstrate the influence of gut microbiota dysbiosis on psychiatric and psychological disorders, and how microbiota-based interventions may be used as potential therapeutic tools.

Recent reassessment of the safety of aspartame has prompted increased evaluation of its effect on the health of a range of tissues. The gut microbiome is altered by oral aspartame. One prior study suggested that changes in the microbiome caused by aspartame could influence the strength of bone in young skeletally developing mice. Here we ask how aspartame influences bone in mice of different age and sex.

The objective of this study was to determine the effect of aspartame on the bone strength and gut microbiota of young and aged mice.

Male and female C57Bl/6J mice were untreated or treated with a high dose of aspartame in their drinking water from 1 month of age until 4 (young cohort; n = 80) or 22 months (aged cohort; n = 52).

In aged males, mice treated with aspartame had greater body mass, whole bone strength, and femoral geometry relative to untreated. Specifically, in aged males, aspartame led to 9% increase in body mass (p < 0.001), 22% increase in whole bone strength (p = 0.006), and 17% increase in section modulus (p < 0.001) relative to untreated mice. Aged males and females receiving aspartame had a different microbiota than untreated mice and a decreased abundance of Odoribacter. No differences in body mass, whole bone strength, or femoral geometry were associated with aspartame dosing in young males or young or aged females.

Aspartame treated aged males had greater whole bone strength and the effect appeared to be explained by greater body mass. Aspartame treatment did not alter whole bone strength in young males or young or aged females despite the aspartame having a similar effect on the microbiota of both aged males and females.