The human gut microbiome (GM) influences host physiology through the production of bioactive metabolites. Increasing evidence links GM dysbiosis to neuropsychiatric disorders (NPDs), including anxiety disorders, major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ), via bidirectional signaling along the gut-brain axis (GBA). Among the pathways connecting gut and brain, the tryptophan-kynurenine pathway (TKP) has emerged as a central inflammatory and neuromodulatory mechanism. During immune activation and dysbiosis, tryptophan metabolism shifts toward kynurenine production, generating metabolites with distinct biological effects. Kynurenic acid (KYNA) exerts neuroprotective actions through NMDA receptor antagonism and reduced oxidative stress, whereas quinolinic acid (QUIN) and 3-hydroxykynurenine (3-HK) promote excitotoxicity, mitochondrial dysfunction, and neurodegeneration. Altered KYNA/QUIN balance appears to represent a transdiagnostic feature across NPDs, with preferential QUIN accumulation in mood disorders and pathological KYNA elevation in SCZ, suggesting potential therapeutic relevance. In parallel, the aryl hydrocarbon receptor (AhR), activated by tryptophan-derived microbial metabolites, regulates intestinal barrier integrity, immune responses, and neuroimmunometabolic signaling, functioning as a molecular link between the GM, immune system, and brain. This review explores the interactions among GM dysbiosis, TKP alterations, mitochondrial dysfunction, and AhR signaling in anxiety disorders, MDD, BD, and SCZ, highlighting their potential as biomarkers and targets for personalized therapies.

Sex- and gender-based immune differences have often been interpreted through a male-female biological binary, overlooking how endocrine signaling dynamically shapes immune function. Gender-affirming hormone therapy (GAHT) offers a unique physiological model to disentangle the effects of sex steroids from chromosomal background and examine immune plasticity in contexts relevant to reproductive health. This hormone-informed framework proposes that estradiol and testosterone regulate immune set-points across innate, adaptive, metabolic, and mucosal compartments. Through genomic and non-genomic signaling via androgen and estrogen receptors (AR, ERα/β), these hormones drive distinct immune outcomes: testosterone dampens type I interferon responses in plasmacytoid dendritic cells and reshapes monocyte inflammatory profiles, while estradiol promotes macrophage polarization and enhances T helper1 (Th1) responses. Hormonal effects are closely coupled to cellular metabolism: androgen signaling acts as a "metabolic brake" on Th17 cells by limiting glutaminolysis, a process reinforced by epigenetic remodeling, and is reflected in shifts in the circulating metabolome, positioning metabolomics as a sensitive tool for monitoring hormone-driven immune adaptation. Regardless, hormones also reshape mucosal barriers and reproductive microbiome composition. GAHT alters vaginal and gut microbial communities and their metabolism, influencing mucosal immunity, local inflammation, and reproductive tract homeostasis, with potential implications for fertility preservation, susceptibility to reproductive tract infections, and long-term genital mucosal health. Collectively, this evidence underscores that human immunity is highly responsive to endocrine context. This review synthesizes evidence linking endocrine trajectories, tissue microenvironments, reproductive biology, and social determinants of health, aiming to advance understanding of immune plasticity and contribute to a more inclusive framework of human immune diversity.

Background: Uterine fibroids (UFs) are the most common benign tumors in women of reproductive age and are associated with abnormal uterine bleeding, infertility, and impaired implantation and endometrial receptivity. However, the contribution of the myometrial microbiome (MM) to fibroid biology and the broader uterine environment remains poorly understood. Materials and Methods: We characterized the paired MM of UF tissue and adjacent healthy myometrium (HM) from 21 women undergoing surgery and integrated serum free fatty acid (FFA) and cytokine profiling. Results: Taxonomic composition and microbial diversity were highly similar between tissues, with no differentially abundant taxa after multiple-testing correction. In contrast, PICRUSt2-based functional prediction indicated tissue-specific differences in microbial metabolic potential: UF tissue showed higher predicted representation of pathways related to L-tyrosine biosynthesis and aromatic amine degradation, whereas HM showed higher predicted representation of coenzyme A and arginine biosynthesis pathways. Patients also exhibited distinct circulating FFA profiles compared with healthy women, and integrative analyses identified phenotype-specific associations among microbial taxa, FFAs, and inflammatory mediators, particularly in women with heavy menstrual bleeding or specific fibroid localizations. Conclusions: These findings suggest that UFs are associated with potential functional remodeling of the MM rather than major taxonomic alterations, which may contribute to changes in the uterine environment relevant to implantation, endometrial receptivity, and reproductive health.

Bile acids (BAs), long recognized for their role in lipid digestion, have recently emerged as key signaling molecules at the interface of host metabolism, immunity, and gut microbiota (GM). BAs are synthesized in hepatocytes and subsequently extensively modified by microbial enzymes in the gut, producing a diverse and dynamic pool that strongly shapes the GM-immune axis. Through activation of receptors such as the Farnesoid X receptor and the G protein-coupled receptor TGR5, BAs regulate inflammation, metabolic pathways, and intestinal immune homeostasis, particularly influencing the balance between regulatory T cells and pro-inflammatory Th17 cells. Microbial transformations, primarily deconjugation and 7α-dehydroxylation, further diversify BA species, modulating receptor affinities and immunoregulatory functions. Dysbiosis-associated alterations in these processes contribute to the pathogenesis of inflammatory disorders, including inflammatory bowel disease (IBD). Consequently, BAs are increasingly recognized as promising biomarkers for monitoring disease activity and predicting therapeutic response, although validation in standardized, prospective cohorts remains necessary. Recent advances in high-resolution analytical techniques, notably high- and ultra-performance liquid chromatography coupled with tandem mass spectrometry (HPLC- and UPLC-MS/MS), have enabled precise, high-throughput quantification of BA species in serum and fecal samples. These methods both deepen mechanistic understanding of BA-mediated immunomodulation and support the development of GM- and BA-targeted therapies. This review emphasizes the central role of BAs in GM-immune axis regulation, delineates their complex interplay with host and microbial factors, and surveys evolving analytical strategies that facilitate their study in health and disease.

Liver transplant (LT) recipients represent a population at elevated cardiovascular (CV) risk, yet conventional assessment tools often fail to capture early myocardial dysfunction. Global longitudinal strain (GLS) has emerged as a sensitive marker of subclinical myocardial dysfunction, although its role in the long-term post-transplant setting remains poorly defined. The study aimed to evaluate left ventricular (LV)-GLS in a population of stable LT recipients with a mild cardiometabolic burden and to explore possible associations with metabolic, lifestyle, inflammatory, and transplant-related variables. A secondary aim was to assess longitudinal GLS variation over a 12-month period. We conducted a cross-sectional observational study in 40 LT recipients. Cardiometabolic parameters, body composition (including bioimpedance analysis), diet (Medi-Lite), physical activity (IPAQ), echocardiography, and levels of circulating inflammatory cytokines were measured. CV risk scores were calculated. GLS impairment was detected in 47.5

Background: Cancer remains one of the leading global health challenges, with lung cancer (LC), breast cancer (BC), and colorectal cancer (CRC) among the most prevalent and deadly malignancies. The intratumoral microbiota (IM), a distinct microbial ecosystem within tumor tissues, has recently emerged as a potential modulator of carcinogenesis, immune responses, and metastatic progression. However, comparative cross-cancer analyses remain limited. Therefore, this study aimed to compare the IM across these cancer types, with particular emphasis on distinguishing metastatic from non-metastatic malignancies, to identify tumor-specific microbial signatures with potential relevance for biomarker discovery, patient stratification, and microbiota-informed therapeutic strategies. Methods: We performed 16S rRNA gene sequencing to profile the IM in formalin-fixed, paraffin-embedded (FFPE) samples from 20 BC patients, 20 CRC patients and 15 non-small cell lung cancer (NSCLC) patients. Results: BC samples exhibited the highest genus-level richness, whereas CRC samples showed significantly greater overall alpha diversity, consistent with the microbial complexity of the gut environment. NSCLC samples displayed the most balanced microbial distribution, as reflected by the highest Shannon index value. Stratification by metastatic status revealed distinct microbial signatures: 16 genera were exclusive to metastatic tumors and 49 to non-metastatic ones. In BC specifically, the class Clostridia and the family Burkholderiaceae were enriched in non-metastatic samples, accompanied by functional shifts in pantothenate and coenzyme A biosynthesis, lysine metabolism, and lipid A pathways. Microbial network analysis further revealed differences in ecological community structure and keystone taxa: Streptococcus spp. predominated as hubs in metastatic tumors, whereas Neisseria spp. were central in non-metastatic networks. Conclusions: Overall, our findings highlight cancer-type and metastasis-specific microbial signatures, supporting a potential role for the IM in tumor progression and offering novel avenues for biomarker discovery and therapeutic targeting.

Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease, is a chronic inflammatory condition with global prevalence and varying incidence. The IBD pathogenesis involves intricate interactions among genetic, host and environmental factors, leading to dysregulated immune responses and chronic intestinal inflammation. Alongside elevated levels of inflammatory cytokines and altered miRNAs expression, more studies highlight significant dysbiosis in both fecal and ileal microbiota of IBD patients. This dysbiosis is characterized by an increase in pro-inflammatory and mucin-degrading bacteria (e.g., Fusobacterium spp., Escherichia spp.) and a decline in short-chain fatty acids (SCFAs) -producing microbes (e.g., Roseburia spp., Faecalibacterium spp.) which play a protective role in gut health. Diet emerges as a key environmental factor influencing IBD onset and progression and recent advancements in"omics" technologies, such as genomics, transcriptomics, and metabolomics, provide a deeper understanding of the molecular interactions between genes, gut microbiota (GM) and nutrition. Finally, new technologies like artificial intelligence (AI), further enhance findings by enabling data integration and personalized dietary strategies. In this scenario, this review aims to summarize accumulating data on the effects of dietary interventions in IBD patients and introduce the role of artificial intelligence (AI) in facilitating precision dietary approaches to improve IBD management.

BACKGROUND:Gut microbiome (GM) dysbiosis and altered circulating free fatty acid (FFA) profiles have been implicated in cardiovascular diseases (CVDs), including systemic arterial hypertension (SAH) and ST-segment elevation myocardial infarction (STEMI). This study evaluated serum short-, medium-, and long-chain fatty acids (SCFAs, MCFAs, and LCFAs) in patients with SAH and STEMI compared with healthy controls (HCs), aiming to identify candidate biomarkers and potential mechanistic links between FFAs, the GM, and cardiovascular health. METHODS:Serum samples from 47 STEMI patients, 17 SAH patients, and 28 HCs were analysed using gas chromatography-mass spectrometry. RESULTS:Principal coordinates analyses (PCoA) showed significant group separation based on FFA profiles. Both STEMI and SAH patients exhibited increased total SCFA levels, with higher acetic, propionic, 2-methylbutyric, and isovaleric acids compared with HCs. Conversely, STEMI patients showed reduced isobutyric and valeric acids versus both HCs and SAH, and lower 2-methylbutyric acid relative to SAH. STEMI patients also had lower total MCFA levels, mainly due to reduced octanoic acid, while both patient groups showed increased hexanoic acid versus HCs. Additionally, STEMI patients showed elevated hexadecanoic acid and reduced octadecanoic acid compared with the other groups.Sparse partial least squares discriminant analysis (sPLS-DA) confirmed distinct FFA signatures: STEMI was characterised by increased propionic, hexadecanoic, and tetradecanoic acids, whereas SAH showed reduced isovaleric, 2-methylbutyric, hexanoic, and isobutyric acids. CONCLUSIONS:These findings indicate disease-specific circulating FFA patterns that may reflect metabolic alterations and underlying pathophysiological mechanisms.

Bullous pemphigoid (BP) is an autoimmune skin disorder marked by antibodies targeting basement membrane proteins BP180 and BP230. Recent evidence suggests a role for the gut-skin axis and microbial metabolites, especially short-chain fatty acids (SCFAs), in modulating skin homeostasis and immune responses. In this study, we investigated the gut permeability and evaluated the circulating free fatty acids (FFAs) in BP patients, along with the assessment of the ability of each FFA to discriminate BP patients from both pemphigus vulgaris (PV) patients and healthy controls (HC). Thirty-six BP patients and 36 sex- and age-matched HC were enrolled. In addition, we used a previously examined cohort of 18 PV patients. FFAs were quantified through gas chromatography-mass spectrometry. Serum zonulin levels were measured by ELISA test and then correlated with FFA levels and clinical markers of disease activity. Receiver operating characteristic (ROC) curve analyses evaluated the diagnostic utility of individual FFAs. BP patients had significantly lower SCFA levels but higher medium-chain (MCFAs) and long-chain fatty acids (LCFAs) than HC. Zonulin levels were elevated in BP and correlated negatively with isovaleric acid. No clear associations emerged between FFAs, zonulin and clinical disease severity. Sparse partial least square discriminant analysis identified propionic, octanoic and octadecanoic acids as key discriminators between BP and both HC and PV serum FFAs. These metabolites achieved ROC AUCs > 0.9, showing a strong diagnostic value. Our findings reveal a pro-inflammatory shift in serum FFA profiles in BP-marked by decreased SCFAs and increased MCFAs/LCFAs-concurrent with elevated gut permeability. The strong diagnostic performance of propionic, octanoic and octadecanoic acids highlights their promise as biomarkers for BP.

Fetal Alcohol Spectrum Disorder (FASD), caused by prenatal alcohol exposure (PAE), produces lasting physical, cognitive, and behavioral impairments. The present study examined effects of early PAE on the gut microbiome (GM) in adolescent mice to identify targets for early intervention. Female C57Bl/6 dams received 10% ethanol during the first 10 days of gestation while controls received water. Fecal and blood samples from adolescent offspring were profiled by 16S rRNA sequencing and gas chromatography-mass spectrometry to characterize microbial composition and short-chain fatty acids (SCFAs). PAE reduced microbial alpha diversity and produced distinct beta diversity patterns versus controls. Metabolomic profiling revealed increased fecal acetate and reduced anti-inflammatory SCFAs in PAE mice, though circulating SCFA levels remained unchanged. Sex-stratified analyses showed that these alterations were driven predominantly by males, who exhibited greater microbial and metabolic disruptions, enrichment of pro-inflammatory genera (Parasutterella, Parabacteroides, Clostridioides), and elevated serum medium-chain fatty acids. Cluster analysis of PAE males identified a dysbiotic subgroup with severe alpha diversity loss, increased pro-inflammatory taxa, diminished beneficial SCFAs, and enrichment of catabolic and fatty acid biosynthesis pathways. Together, the results reveal sex- and individual-specific susceptibility to PAE-induced GM dysbiosis and justify further mechanistic studies to develop sex-tailored microbiota-targeted strategies for FASD.

BACKGROUND AND AIM:Advances in human microbiome research have highlighted its influence on host health. This study aimed to characterize the oral microbiome (OM) and gut microbiome (GM) and to examine their relationships with systemic fatty acid and cytokine profiles across different age groups in healthy adults. METHODS:Participants aged 18-76 years without diagnosed diseases were grouped into young (18-29 years), middle-aged (30-49 years), and older adults (≥50 years). Blood, dental plaque, and fecal samples were collected. OM and GM composition were evaluated using 16 rRNA sequencing. Circulating free fatty acids (FFAs) were quantified by gas chromatography-mass spectrometry, and serum cytokines were assessed using flow cytometry. RESULTS:In the OM, Fusobacterium and Haemophilus were notably abundant in young adults, while Haemophilus and Neisseria predominated in middle-aged adults. In older adults, Neisseria and Capnocytophaga were the most prevalent oral genera. In the GM, Bacteroides was the most prevalent genus across all age groups, followed by Faecalibacterium, Blautia, and Prevotella_9. Additionally, circulating levels of decanoic, hexadecanoic, and octadecanoic acids, as well as the cytokine IP-10, were higher in young adults compared with the other age groups. CONCLUSION:To our knowledge, this study is the first to characterize and correlate the diversity of both the OM and GM with systemic FFA and cytokine profiles in a cohort of healthy adults, highlighting the critical role of age in shaping microbiome composition and associated metabolites. Integrating microbial profiling with serum FFA and cytokine measurements enhances our understanding of how the microbiome may influence health and disease risk across the adult lifespan.

Oxygen availability is a key regulator of organ maturation during the perinatal period. Disruption of physiological oxygen homeostasis contributes to prematurity-associated disorders, yet its effects on the coordinated maturation of the enteric nervous system (ENS) and gut microbiome remain poorly understood. Because β3-adrenergic receptor (β3-AR) signaling has emerged as a mediator of tissue adaptation to oxygen, we investigated whether activation of this pathway modulates hyperoxia-induced alterations in the developing colon. Newborn rats were exposed to normoxia or hyperoxia (85% O2) from birth to postnatal day 14 and treated with the β3-AR agonist BRL37344 (1 or 3 mg/kg). Enteric neuronal and glial populations were evaluated by quantitative immunofluorescence, whereas the colonic microbiome (CM) was characterized by 16S rRNA gene sequencing. Hyperoxia reduced neuronal density and altered neurochemical coding within the submucosal plexus, disrupted enteric glial organization in both the colonic submucosal plexus and mucosa, and remodeled the intestinal microbiome without affecting overall community diversity. BRL37344 treatment partially preserved submucosal neurochemical coding, modulated neuron–glia organization within the submucosal plexus, prevented the loss of mucosal enteric glial cells, and reshaped microbial composition. Collectively, these findings demonstrate that neonatal hyperoxia disrupts coordinated postnatal maturation of the ENS and CM and indicate that β3-AR signaling may contribute to postnatal intestinal adaptation to neonatal oxygen imbalance.

Brain tumors (BTs), including glioblastoma (GBM) and meningioma (MGM), contribute significantly to the global cancer burden. The microbiome has been implicated in carcinogenesis, yet its role in BTs remains underexplored. We performed 16S rRNA gene sequencing of the gut microbiota (GM) and intratumoral microbiome (ItM) from fresh tissue samples of 9 patients with GBM and 18 with MGM. 12 age- and sex-matched healthy controls (HCs) were also enrolled. GM profiling revealed reduced alpha diversity and distinct microbial communities in BT patients versus HCs. Notably, Verrucomicrobiota and Synergistaceae were enriched, while Lachnospiraceae, Peptostreptococcaceae, and Muribacter spp. were depleted. GBM patients showed reductions in Peptostreptococcaceae and the Eubacterium hallii group, while MGM patients had increased Synergistia and Erysipelatoclostridium. Compared with MGM, GBM patients were enriched in Peptostreptococcales-Tissierellales, Coprobacillus, and Peptoniphilus but depleted in Weissella. Venn analysis revealed 176 genera shared across groups with unique taxa distinguishing tumor patients and HCs. ItM profiling revealed enrichment of Proteobacteria, Actinomycetota, and Campylobacterota in GBM, while MGM contained higher levels of Bacillota and Bacteroidota. GBM tissues harbored Burkholderia-Caballeronia-Paraburkholderia, Helicobacter, and Leifsonia, whereas MGM tissues were dominated by Bacteroides and Blautia. Notably, stool and tumor samples shared 91 genera in GBM and 105 in MGM. This study provides novel insights by (i) characterizing ItM from fresh samples, (ii) comparing ItM profiles of GBM and MGM, (iii) linking GM and ItM within the same patients, and (iv) suggesting potential clinical implications for BT management.

The clinical adenoma - carcinoma progression represents a well-established framework for understanding colorectal cancer (CRC) development, although the molecular mechanisms underlying this transition remain only partially understood. Increasing evidence suggests the gut microbiome (GM) as a key modulator of colorectal carcinogenesis, positioning microbial profiling as a promising avenue for noninvasive risk stratification and early detection. In this study, Machine Learning (ML) classifiers integrated with eXplainable Artificial Intelligence (XAI) techniques were employed to identify microbiome-derived biomarkers predictive of CRC and adenomatous lesions. The models were trained on 16S rRNA sequencing data from 453 patients and evaluated through cross-validation, achieving AU-ROC and AU-PRC scores of 0.71 and 0.67, respectively. External validation on an independent Italian cohort (n=43) yielded AU-ROC and AU-PRC scores of 0.70 and 0.89, respectively. XAI-based interpretation revealed consistent microbial signatures across datasets. In detail, taxa belonging to the Fusobacterium and Peptostreptococcus genera were associated with increased CRC risk, whereas the Eubacterium eligens group was identified as a robust negative predictor. Beyond classification, patient-level explanations enabled by XAI facilitated the identification of adenoma subgroups exhibiting microbiome profiles converging toward those of CRC, suggesting the presence of transitional microbial states. Moreover, SHAP-based interaction networks uncovered microbial hubs and inter-species dependencies characterizing high-risk configurations, providing insights into the ecological dynamics of colorectal tumorigenesis. These findings demonstrate the added XAI value in elucidating microbiome interactions, enhancing model interpretability, and supporting biologically informed hypotheses. This integrative, explainable framework highlights the potential of AI-driven microbiome analysis in precision oncology and advances the development of interpretable, noninvasive tools for CRC risk prediction and management.

BACKGROUND AND AIMS:Atrial fibrillation (AF), heart failure (HF), and undernutrition represent a complex triad with major clinical and socioeconomic consequences in older adults, often predisposing to frailty. Undernutrition often remains underdiagnosed due to a reliance on weight-based measures and limited awareness of inflammation-related cachexia. The AMBROSIA study aims to fill these gaps by exploring the response of the microbiota-inflammation-brain axis to a targeted, fortified food product-based intervention, with comprehensive outcome assessments, alongside mechanistic/exploratory -omics analyses and gut microbiota (GM) functional profiling. METHODS AND RESULTS:This single-center, prospective, parallel-group randomized controlled trial aims to enroll 120 older adults with confirmed AF and/or HF. Participants will be randomized 1:1 into an intervention group (n = 60) or control group (n = 60). All participants receive individualized dietary counseling; the intervention group additionally consumes one AMBROSIA nutritional bar daily for six months. The bar contains hydrolyzed proteins, inulin, CoQ₁₀, and probiotics (L. rhamnosus IMC 501® and L. paracasei IMC 502®) in a flavonoid-rich chocolate matrix. Clinical, cognitive, and nutritional data, along with blood, saliva, urine, and stool samples, will be collected at baseline, 3, and 6 months. The primary endpoint is the change in skeletal muscle mass, physical function and frailty, while secondary endpoints include changes in nutritional status, inflammation, GM, metabolomics, and quality of life. CONCLUSION:By integrating cutting-edge omics tools and a multidimensional nutritional strategy, AMBROSIA aims to uncover mechanisms driving undernutrition and identify biomarkers to support personalized interventions for older patients with AF and HF.

Acute myocardial infarction (AMI) is a leading cause of mortality in Mexico. The microbiota plays a crucial role in immune regulation, and its dysbiosis promotes low-grade inflammation, a key contributor to AMI development. This study aimed to compare the oral (OM) and gut microbiota (GM) composition in patients with ST-segment elevation myocardial infarction (STEMI) and healthy controls. Additionally, we explored the interaction between these microbiomes and their correlations with inflammatory profiles and metabolites. In this study, we included 36 STEMI patients and 12 healthy subjects. The composition of both GM and OM was analyzed through 16S sequencing of dental plaque and stool samples. Short-chain fatty acids (SCFAs) were measured via gas chromatography-mass spectrometry, while serum cytokines were assessed using flow cytometry. STEMI patients exhibited significant differences in OM alpha and beta diversity, while GM structure remained unchanged compared to healthy group. Several differentially abundant genera were identified in both OM and GM. Regarding SCFA profiles, Healthy subjects displayed a higher abundance of isovaleric acid, whereas isobutyric and 2-methylbutyric acids were significantly higher in STEMI patients. Moreover, correlations between circulating SCFAs, cytokines, and microbiota composition were observed in both niches. Furthermore, network analysis suggests that oral bacteria, particularly those linked to periodontal disease, can potentially influence GM by interacting with SCFA-producing bacteria. This is the first study in México to comprehensively explore OM and GM in STEMI patients. Our findings highlight the potential for developing preventive strategies against myocardial infarction by exploring both oral and gut microbiomes, as well inflammatory markers and SCFAs.

Background/Objectives: Breast cancer (BC) is the leading cause of cancer incidence and mortality among women and the recent identification of a resident mammary microbiota has highlighted its potential role in breast carcinogenesis. Given that environmental and socioeconomic factors influence both BC prevalence and tumor-associated bacterial composition, this study aimed to evaluate the compositional and functional features of the mammary microbiota in cancerous (oncobiome) and adjacent healthy BC tissues from patients living in urban and rural areas. Methods: Microbiota composition in both the oncobiome and adjacent healthy BC tissues was analyzed using 16S rRNA sequencing. Results: Significant variations in breast oncobiome composition were observed among BC patients from urban and rural areas. A statistically significant β dispersion among breast oncobiome of patients from urban or rural areas was highlighted. Specifically, the genera Selenomonas, Centipeda, Leptotrichia, Neisseria and Porphyromonas were found exclusively in BC tissues of patients from rural areas. Additionally, bacteria from the Neisseriaceae, Porphyromonadaceae, and Selenomonadaceae families, as well as the Selenomonas genus, were significantly enriched in the oncobiome of rural BC patients. Furthermore, the results of the PICRUSt2 (phylogenetic investigation of communities by reconstruction of unobserved states) revealed a significant increase in phospholipid biosynthesis pathways in breast oncobiome of patients from rural areas compared to those from urban areas. Conclusions: This study provides evidence of distinct compositional and functional differences in the breast oncobiome between BC patients from rural and urban areas. These findings suggest that environmental factors influence local microbiome composition, potentially contributing to BC development and/or progression.

BACKGROUND:Gut microbiota (GM) affects muscle homeostasis, and growing evidence indicates dysbiosis of GM may be a contributing factor in the pathogenesis of dystrophies. Furthermore, GM metabolites can interact with DNA methylation. Facioscapulohumeral muscular dystrophy (FSHD) is the second common dystrophy with hypomethylation of DR1 and 5P regions of D4Z4 repeat on 4qter. OBJECTIVE:Considering alteration of GM may be a contributing factor, we investigated (i) GM alterations and (ii) the correlation of microbial-derived free fatty acids (FFAs) with methylation of DR1 and 5P regions in FSHD. METHODS:Twenty-eight FSHD patients and 28 gender-age-matched controls were included. GM characterisation was performed through 16S-rRNA sequencing. Methylation levels of DR1 and 5P regions were assessed by bisulphite sequencing. Faecal and circulating FFAs including short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs) and long-chain fatty acids (LCFAs) were analysed with gas chromatography-mass spectrometry. RESULTS:Altered GM was observed in patients, along with distinct profiles of faecal and circulating SCFAs, MCFAs and LCFAs. DR1 and 5P regions exhibited significant hypomethylation in FSHD compared to control. Hypomethylation correlated with faecal and circulating FFAs in patients, while no correlation was identified in healthy controls. The severely affected patients exhibited a notable increase in the prevalence of Pasteurellaceae, while the FFA profile was similar among mild and severely affected patients. This is the first study revealing that FSHD patients showed compositional and functional GM dysbiosis. A strong association between proximal D4Z4 hypomethylation with microbial-derived SCFAs was identified. CONCLUSION:These findings suggest that GM modulation with its metabolites could be a promising strategy for interventions in FSHD management.

Obesity and dyslipidemia are increasingly widespread. Considering gut microbiota's (GM) role in energy balance, probiotics represent a promising non-pharmacological approach. This study assessed a probiotic formulation (SF68 + phytosterols + (6S)-5-methyltetrahydrofolic acid) on anthropometric, biochemical, and GM parameters, as well as gastrointestinal and general symptoms, in overweight/obese individuals with low-to-moderate cardiovascular risk. Forty participants (30F, mean age 51.5 ± 11 years) were randomized to receive either the probiotic or placebo daily for 12 weeks. Anthropometric data, questionnaires, and biological samples were collected pre- and post-intervention. While both groups showed significant (p < 0.05) improvements, the probiotic group showed greater reductions in waist circumference (-1.8 cm), fat mass (-1.8 kg; -1.7%), total cholesterol (-11 mg/dL), and LDL-cholesterol (-10.3 mg/dL), along with an increased HDL/LDL ratio (+0.1). Both probiotic and placebo resulted in a significant reduction in HbA1c (-1.7 mmol/mol and -1.5 mmol/mol, respectively). The probiotic formulation also reduced erythrocyte ROS (-29.7%), granulocyte ROS (-28.4%), and plasma nitrite/nitrate (49.5%) and significantly increased erythrocyte glutathione (GSH; +81.9%). Gastrointestinal symptoms improved, and GM analysis showed an increased Evenness index and reduced Lachnospirales abundance after probiotic treatment. These findings suggest the multi-component probiotic formulation may support metabolic and gut health in overweight or obese individuals, although further research is warranted.