Candida albicans (C. albicans) exhibits aberrant changes in patients with colitis, and it has been reported to dominate the colonic mucosal immune response. Here, we found that PMA1 expression was significantly increased in C. albicans from patients with IBD compared to that in healthy controls. A Crispr-Cas9-based fungal strain editing system was then used to knock out PMA1 expression in C. albicans. Compared to WT-C.a, ΔPMA1-C.a could not aggravate colitis. Proteomic analysis showed that PMA1 was transported by extracellular vesicles (EVs) of C. albicans. PMA1-containing EVs aggravated colitis, modulated the migration of cDC2 from the lamina propria to mesenteric lymph nodes, and induced TH17 cell differentiation. Moreover, the adaptor protein CARD9 was critical in PMA1-containing EV-induced colitis, and CARD9-deficient DCs did not induce TH17 cell differentiation or IL-17A production. Mechanically, CARD9 combines with the glycolytic protein GAPDH (aa2-146 domain) through its CARD region. CARD9 deficiency led to decreased enzyme activity of GAPDH and decreased glycolysis of DCs. These findings indicate that PMA1 is a potential virulence factor responsible for the pathogenesis of C. albicans colitis.

Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment.

The gut microbiome, composed of bacteria, fungi, and viruses, plays a crucial role in maintaining the delicate balance of human health. Emerging evidence suggests that microbiome disruptions can have far-reaching implications, ranging from the development of inflammatory diseases and cancer to metabolic disorders. Bacteriophages, or "phages", are viruses that specifically infect bacterial cells, and their interactions with the gut microbiome are receiving increased attention. Despite the recently revived interest in the gut phageome, it is still considered the "dark matter" of the gut, with more than 80% of viral genomes remaining uncharacterized. Today, research is focused on understanding the mechanisms by which phages influence the gut microbiota and their potential applications. Bacteriophages may regulate the relative abundance of bacterial communities, affect bacterial functions in various ways, and modulate mammalian host immunity. This review explores how phages can regulate bacterial functionality, particularly in gut commensals and pathogens, emphasizing their role in gut health and disease.

Clostridioides difficile infection (CDI) has been recognized as a leading cause of healthcare-associated infections and a considerable threat to public health globally. Increasing evidence suggests that the gut microbiota plays a key role in the pathogenesis of CDI. The taxonomic composition and functional capacity of the gut microbiota associated with CDI have not been studied systematically. Here, we performed a comprehensive shotgun metagenomic sequencing in a well-characterized human cohort to reveal distinct patterns of gut microbiota and potential functional features associated with CDI. Fecal samples were collected from 104 inpatients, including : (1) patients with clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment (CDI, n = 47); (2) patients with positive stool NAAT but without diarrhea (Carrier, n = 17); (3) patients with negative stool NAAT but with diarrhea (Diarrhea, n = 14); and (4) patients with negative stool NAAT and without diarrhea (Control, n = 26). Downstream statistical analyses (including alpha and beta diversity analysis, differential abundance analysis, correlation network analysis, and potential functional analysis) were then performed. The gut microbiota in the Control group showed higher Chao1 index (p < 0.05), while Shannon index at KEGG module level was higher in CDI than in Carrier and Control (p < 0.05). Beta diversity for species composition differed significantly between CDI vs Carrier/Control cohorts (p < 0.05). Microbial Linear discriminant analysis Effect Size and ANCOM analysis both identified 8 species (unclassified_f_Enterobacteriaceae, Veillonella_parvula, unclassified_g_Klebsiella and etc.) were enriched in CDI, Enterobacter_aerogenes was enriched in Diarrhea, Collinsella_aerofaciens, Collinsella_sp_4_8_47FAA, Collinsella_tanakaei and Collinsella_sp_CAG_166 were enriched in Control (LDA >3.0, adjusted p < 0.05). Correlation network complexity was higher in CDI with more negative correlations than in other three cohorts. Modules involved in iron complex transport system (M00240) was enriched in CDI, ABC-2 type transport system (M00254), aminoacyl-tRNA biosynthesis (M00359), histidine biosynthesis (M00026) and inosine monophosphate biosynthesis (M00048) were enriched in Carrier, ribosome (M00178 and M00179) was enriched in Diarrhea, fluoroquinolone resistance (M00729) and aminoacyl-tRNA biosynthesis (M00360) were enriched in Control (LDA > 2.5, adjusted p < 0.05). Resistance functions of acriflavine and glycylcycline were enriched in CDI, while resistance function of bacitracin was enriched in Carrier (LDA > 3.0, adjusted p < 0.05), and the contributions of phylum and species to resistance functions differed among the four groups. Our results reveal alterations of gut microbiota composition and potential functions among four groups of differential colonization/infection status of Clostridioides difficile. These findings support the potential roles of gut microbiota and their potential functions in the pathogenesis of CDI.

Roseburia intestinalis is one of the most abundant and important butyrate-producing human gut anaerobic bacteria that plays an important role in maintaining health and is a potential next-generation probiotic. We investigated the pangenome of 16 distinct strains, isolated over several decades, identifying local and time-specific adaptations. More than 50% of the genes in each individual strain were assigned to the core genome, and 77% of the cloud genes were unique to individual strains, revealing the high level of genome conservation. Co-carriage of the same enzymes involved in carbohydrate binding and degradation in all strains highlighted major pathways in carbohydrate utilization and reveal the importance of xylan, starch and mannose as key growth substrates. A single strain had adapted to use rhamnose as a sole growth substrate, the first time this has been reported. The ubiquitous presence of motility and sporulation gene clusters demonstrates the importance of these phenotypes for gut survival and acquisition of this bacterium. More than half the strains contained functional, potentially transferable, tetracycline resistance genes. This study advances our understanding of the importance of R. intestinalis within the gut ecosystem by elucidating conserved metabolic characteristics among different strains, isolated from different locations. This information will help to devise dietary strategies to increase the abundance of this species providing health benefits.

The enteric microbiota is an established reservoir for multidrug-resistant organisms that present urgent clinical and public health threats. Observational data and small interventional studies suggest that microbiome interventions, such as fecal microbiota products and characterized live biotherapeutic bacterial strains, could be an effective antibiotic-sparing prevention approach to address these threats. However, bacterial colonization is a complex ecological phenomenon that remains understudied in the context of the human gut. Antibiotic resistance is one among many adaptative strategies that impact long-term colonization. Here we review and synthesize evidence of how bacterial competition and differential fitness in the context of the gut present opportunities to improve mechanistic understanding of colonization resistance, therapeutic development, patient care, and ultimately public health.

The gut-brain axis (GBA) denotes the dynamic and bidirectional communication system that connects the gastrointestinal tract and the central nervous system (CNS). This review explored this axis, focusing on the role of microbial diversity and fitness in maintaining gastrointestinal health and preventing neurodegeneration, particularly in Alzheimer's disease (AD). Gut dysbiosis, characterized by the imbalance in populations of beneficial and harmful bacteria, has been associated with increased systemic inflammation, neuroinflammation, and the progression of AD through pathogenic mechanisms involving amyloid deposition, tauopathy, and increased blood-brain barrier (BBB) permeability. Emerging evidence highlighted the therapeutic potential of probiotics, dietary interventions, and intermittent fasting in restoring microbial balance, reducing inflammation, and minimizing neurodegenerative risks. Probiotics and synbiotics are promising in helping improve cognitive function and metabolic health, while dietary patterns like the Mediterranean diet were linked to decreased neuroinflammation and enhanced gut-brain communication. Despite significant advancement, further research is needed to elucidate the specific microbial strains, metabolites, and mechanisms influencing brain health. Future studies employing longitudinal designs and advanced omics technologies are essential to developing targeted microbiome-based therapies for managing AD-related disorders.

Cardiovascular diseases (CVDs), including hypertension, atherosclerosis, and cardiomyopathy among others, remain the leading cause of global morbidity and mortality. Despite advances in treatment, the complex pathophysiology of CVDs necessitates innovative approaches to improve patient outcomes. Recent research has uncovered a dynamic interplay between mitochondria and gut microbiota, fundamentally altering our understanding of cardiovascular health. However, while existing studies have primarily focused on individual components of this axis, this review examines the bidirectional communication between these biological systems and their collective impact on cardiovascular health. Mitochondria, serving as cellular powerhouses, are crucial for maintaining cardiovascular homeostasis through oxidative phosphorylation (OXPHOS), calcium regulation, and redox balance. Simultaneously, the gut microbiota influences cardiovascular function through metabolite production, barrier integrity maintenance, and immune system modulation. The mitochondria-gut microbiota axis operates through various molecular mechanisms, including microbial metabolites such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFA), and secondary bile acids, which directly influence mitochondrial function. Conversely, mitochondrial stress signals and damage-associated molecular patterns (DAMPs) affect gut microbial communities and barrier function. Key signalling pathways, including AMP-activated protein kinase (AMPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and the silent information regulator 1-peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1-PGC-1α) axis, integrate these interactions, highlighting their role in CVD pathogenesis. Understanding these interactions has revealed promising therapeutic targets, suggesting new therapies aimed at both mitochondrial function and gut microbiota composition. Thus, this review provides a comprehensive framework for leveraging the mitochondria-gut microbiota axis in providing newer therapeutics for CVDs by targeting the AMPK/SIRT-1/PGC-1α/NF-κB signalling.

The integration of microbiome research and nanotechnology represents a significant advancement in immuno-oncology, potentially improving the effectiveness of cancer immunotherapies. Recent studies highlight the influential role of the human microbiome in modulating immune responses, presenting new opportunities to enhance immune checkpoint inhibitors (ICIs) and other cancer therapies. Nanotechnology offers precise drug delivery and immune modulation capabilities, minimizing off-target effects while maximizing therapeutic outcomes. This review consolidates current knowledge on the interactions between the microbiome and the immune system, emphasizing the microbiome's impact on ICIs, and explores the incorporation of nanotechnology in cancer treatment strategies. Additionally, it provides a forward-looking perspective on the synergistic potential of microbiome modulation and nanotechnology to overcome existing challenges in immuno-oncology. This integrated approach may enhance the personalization and effectiveness of next-generation cancer treatments, paving the way for transformative patient care.

The human microbiome is crucial in regulating intestinal and systemic functions. While its role in cardiovascular disease is better understood, the link between intestinal microbiota and valvular heart diseases (VHD) remains largely unexplored.

Peer-reviewed studies on human, animal or cell models analysing gut microbiota profiles published up to April 2024 were included. Eligible studies used 16S rRNA or shotgun sequencing, metabolite profiling by mass spectrometry, and examined osteogenesis or fibrosis signalling in valve cells. Methods and findings were qualitatively analysed, with data charted to summarize study design, materials and outcomes.

Thirteen studies were included in the review: five human, three animal and five in vitro. Of the nine studies on calcific aortic stenosis (CAS), elevated trimethylamine N-oxide (TMAO) levels were linked to an increased risk of cardiovascular events in cohort studies, with CAS patients showing higher levels of Bacteroides plebeius, Enterobacteriaceae, Veillonella dispar and Prevotella copri. In vivo, TMAO promoted aortic valve fibrosis, while tryptophan derivatives stimulated osteogenic differentiation and interleukin-6 secretion in valvular interstitial cells. Two studies on rheumatic mitral valve disease found altered microbiota profiles and lower short-chain fatty acid levels, suggesting potential impacts on immune regulation. Two studies on Barlow's mitral valve disease in animal models revealed elevated TMAO levels in dogs with congestive heart failure, reduced Paraprevotellaceae, increased Actinomycetaceae and dysbiosis involving Turicibacter and E. coli.

TMAO has been mainly identified as a prognostic marker in VHD. Gut microbiota dysbiosis has been observed in various forms of VHD and deserve further study.

Childhood obesity is a considerable public health issue. Recent research has shown that alterations in gut microbiota can have an impact on developing obesity and other metabolic health problems in children. This study aimed to investigate whether the characteristics of gut microbiota in obese children and adolescents are associated with the severity of obesity and any metabolic complications.

During May 2022 to May 2023, a total of 56 children and adolescents with obesity, aged 6-18 years, were recruited at Thammasat Hospital, situated in provincial Pathumthani in central Thailand. Participants were allocated into two groups, characterized by the severity of their obesity. Demographic data, body composition, along with resting energy expenditures were determined. Serum samples were collected for the metabolic profile and inflammatory markers. Fecal samples were obtained for gut microbiota analysis via 16S rRNA Illumina. The obese group exhibited notably greater relative abundance of Actinobacteriota in comparison to the severely obese group, along with a lower abundance of Bacteroidota. There were no statistically significant differences in the relative abundance of Firmicutes and the Firmicutes to Bacteroidota ratio between the two cohorts. Bacteroidota positively correlated with FMI, while Actinobacteriota showed a negative correlation with FMI.

The data gathered from this study illustrated that children and adolescents with obesity and severe obesity in Thailand showed differences in the relative abundance of Actinobacteriota and Bacteroidota. Certain microbiome taxa showed correlations with various body and metabolic parameters.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become a major health risk and a serious worldwide issue. MAFLD typically arises from aberrant lipid metabolism, insulin resistance, oxidative stress, and inflammation. However, subjacent causes are multifactorial. The gut has been proposed as a major factor in health and disease, and over the last decade, bacterial strains with potentially beneficial effects on the host have been identified. In vitro cell models have been commonly used as an early step before in vivo drug assessment and can confer complementary advantages in gut and liver health research. In this study, several selected strains of the order Bacteroidales were used in a three-cell line in vitro analysis (HT-29, Caco-2, and HepG2 cell lines) to investigate their potential as new-generation probiotics and microbiota therapeutics. Antimicrobial activity, a potentially useful trait, was studied, and the results showed that Bacteroidales can be a source of either wide- or narrow-spectrum antimicrobials targeting other closely related strains. Moreover, Bacteroides sp. 4_1_36 induced a significant decrease in gut permeability, as evidenced by the high TEER values in the Caco-2 monolayer assay, as well as a reduction in free fatty acid accumulation and improved fatty acid clearance in a steatosis HepG2 model. These results suggest that Bacteroidales may spearhead the next generation of probiotics to prevent or diminish MAFLD.

Recently, it has been reported that oral probiotics improve the apparent digestibility of nitrogen in weaned piglets; however, the underlying mechanism is unclear. A total of 12 crossbred piglets (Yorkshire × Landrace; 28 days old) were randomly divided into two groups. The control (Con) group was fed with a basic diet + Luria-Bertani (LB; sterile; 10 mL), whereas the subject (Sub) group was fed with a basic diet + B. subtilis JATP-3 (1 × 109 CFU/mL; 10 mL). The results showed that feeding B. subtilis JATP-3 increased the final body weight and nitrogen deposition rate of weaned piglets (P < 0.05); while the daily weight gain showed an upward trend (P < 0.1). The abundance of Pedicoccus, Collinella, Turiciator, Veillonella, Clostridium, and Escherichia were significantly increased in the jejunum (P < 0.05). The abundance of Olsenella and Pediococcus were significantly increased in the ileum (P < 0.05). The metabolomics analysis showed that the levels of l-lactic acid and Alpha-ketoglutaric acid (AKG) in portal vein plasma were significantly increased (P < 0.05). In addition, the content of AKG in muscle and liver increased significantly (P < 0.01). The metagenomics analysis showed that Veillonella encoded the functional genes of 2-oxoglutarate synthase and promoted AKG production. The protein expression of eIF4E-binding protein 1 (4EBP1) phosphorylated in the skeletal muscle increased (P < 0.05). In summary, B. subtilis JATP-3 promotes dietary nitrogen metabolism and skeletal muscle synthesis by modulating the intestinal microbiota and its metabolites, in which AKG may be one of the main mediators of the therapeutic effects of B. subtilis JATP-3.

Diabetes mellitus, a most common endocrine disorder of glucose metabolism, has become a global epidemic and poses a serious public health threat with an increased socio-economic burden. Escalating incidence of diabetes is correlated with changes in lifestyle and food habits that cause gut microbiome dysbiosis and β-cells damage, which can be addressed with dietary interventions containing probiotics. Hence, the search for probiotics of human origin with anti-diabetic, anti-AGE, and anti-ACE potentials has gained renewed interest for the effective management of diabetes and its associated complications. The present study used an alloxan (AXN)-induced diabetic rat model to investigate the effects of potential probiotic Lacticaseibacillus casei MKU1, Lactiplantibacillus pentosus MKU3, and Lactiplantibacillus plantarum MKU7 administration individually on physiochemical parameters related to diabetic pathogenesis. Experimental animals were randomly allotted into six groups viz. NCG (control), DCG (AXN), DGM (metformin), DGP1 (MKU1), DGP2 (MKU3), and DGP3 (MKU7), and biochemical data like serum glucose, insulin, AngII, ACE, HbA1c, and TNF-α levels were measured until 90 days. Our results suggest that oral administration with MKU1, MKU3, or MKU7 significantly improved serum insulin levels, glycemic control, glucose tolerance, and body weight. Additionally, β-cell mass was increased by preserving islet integrity in Lactobacillus-treated diabetic rats, whereas TNF-α (~40%), AngII (~30%), and ACE levels (~50%) were strongly inhibited and enhanced sIgA production (5.8 folds) abundantly. Furthermore, Lactobacillus administration positively influenced the gut microbiome with a significant increase in the abundance of Lactobacillus species and the beneficial Bacteroides uniformis and Bacteroides fragilis, while decreased the pathogenic Proteus vulgaris and Parabacteroides distasonis. Among the probiotic treatment groups, L. pentosus MKU3 performed greatly in almost all parameters, indicating its potential use for alleviating diabetes-associated complications.

Anxiety disorders are mental health disorders characterized by long-lasting fear, worry, nervousness, and alterations in gut microbiota (GM). The GM is a vital modulator of brain function through the gut-brain axis, which acts as the neural pathway between the central and peripheral nervous systems. Dysbiosis of GM plays an essential role in anxiety development because of alterations in the vagus nerve, increased intestinal permeability, and altered breakdown of tryptophan (TRP). The Kynurenine (KYN) pathway plays a crucial role in the pathogenesis of anxiety disorders, primarily through its neuroprotective (KYNA) and neurotoxic (QUIN) metabolites. Higher ratios of KYNA/QUIN result in neuroprotection, whereas higher KYN/TRP ratios indicate increased QUIN production causing neuroinflammation. Studies on germ-free models exhibit higher plasma TRP levels, which interrupt the metabolic balance of TRP-derived compounds, thus causing brain impairment. A key issue in anxiety disorders is the dysregulation of GM, which disrupts TRP metabolism and neuroinflammatory pathways, however, remains poorly understood. Hence, the proper understanding of these mechanisms is crucial for future therapeutic advancements. Here, we highlight the significance of the TRP-KYN pathway and the potential of modulating KYN pathway enzymes, such as kynurenine aminotransferases (KATs), to adjust KYNA levels and restore neurotransmitter balance. It further discusses new therapeutic methods with a particular focus on probiotics that may restore GM and modulate TRP metabolism. Advancing our understanding of the intricate relationship between GM and anxiety disorders may facilitate novel, microbiota-targeted interventions. This ultimately contributes to precision medicine approaches in mental health care, thereby enhancing treatment efficacy and patient outcomes.

Postmenopausal osteoporosis (PMOP) is a systemic metabolic bone disease caused by the decrease in estrogen levels after menopause. It leads to bone loss, microstructural damage, and an increased risk of fractures. Studies have found that the gut microbiota and its metabolites can regulate bone metabolism through the gut-bone axis and the gut-brain axis. As research progresses, PMOP has been found to be associated with gut microbiota dysbiosis and Th17/Treg imbalance. The gut microbiota is closely related to the development and differentiation of Treg and Th17 cells. Among them, the metabolites of the gut microbiota such as short-chain fatty acids (SCFAs) can regulate the differentiation of effector T cells by acting on molecular receptors on immune cells, thereby regulating the bone immune process. The multifaceted relationship among the gut microbiota, SCFAs, Th17/Treg cell-mediated bone immunity, and bone metabolism is eliciting attention from researchers. Through a review of existing literature, we have comprehensively summarized the effects of the gut microbiota and SCFAs on PMOP, especially from the perspective of Th17/Treg balance. Regulating this balance may provide new opportunities for PMOP treatment.

Microglia-mediated neuroinflammation is crucial for obstructive sleep apnea (OSA)-induced cognitive impairment. We aimed to investigate roles of acetate (ACE) and SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) in neuroinflammation of OSA.

After C57BL/6J mice were exposed to OSA-associated intermittent hypoxia (IH) or normoxia for four weeks, the composition of the gut microbiota (GM) and the levels of serum short-chain fatty acids (SCFAs) were measured by 16S rRNA and GC-MS methods, respectively. To assess the effect of ACE on IH mice, glyceryl triacetate (GTA) was gavaged in IH-exposed mice and the cognitive function, microglial activation, and hippocampal neuronal death were examined. Moreover, ACE-treated BV2 microglia cells were also utilized for further mechanistic studies.

IH disrupts the gut microbiome, reduces microbiota-SCFAs, and impairs cognitive function. Gavage with GTA significantly mitigated these cognitive deficits. Following IH exposure, we observed substantial increases in SETDB1 both in vivo and in vitro, along with elevated levels of histone H3 lysine 9 trimethylation (H3K9me3). Genetic or pharmacological inhibition of SETDB1 in microglia led to decreased induction of proinflammatory factors, as well as reduced reactive oxygen species (ROS) generation. Mechanistically, SETDB1 was found to upregulate the transcription factors p-signal transducer and activator of transcription 3 (p-STAT3) and p-NF-κB. In vitro, ACE supplementation effectively repressed high SETDB1 and H3K9me3 levels, thereby inhibiting microglial pro-inflammatory responses induced by IH. In vivo, ACE supplementation significantly reduced hippocampal levels of p-STAT3, p-NF-κB, and pro-inflammatory cytokines while also protecting neuronal integrity.

This study provides the first evidence that H3K9 methyltransferase SETDB1 promotes microglial pro-inflammatory response distinct from its previously shown role in macrophages. Our findings also identify ACE supplementation as a promising dietary intervention for OSA-related cognitive impairment with SETDB1 serving as both a mechanistic biomarker and potential therapeutic target.

Type 2 diabetes presents significant public health challenges. The gut microbiome has emerged as a potential factor influencing glucose metabolism.

We performed a randomized, double-blind, single-center trial involving patients with type 2 diabetes and glycated hemoglobin (HbA1c) concentration of 7 % or greater. Patients were randomly assigned to receive 100 billion colony-forming units (CFUs) of probiotic supplementation daily or placebo. The primary efficacy endpoint was the change in HbA1c from baseline to 12 weeks, and secondary endpoints included lipid and inflammatory markers.

A total of 130 patients were included. HbA1c was 7.63 ± 0.54 % at baseline and 7.63 ± 0.63 % at 12 weeks in the probiotic group and 7.71 ± 0.74 % and 7.81 ± 0.84 % in the placebo group (p = 0.29 between treatment groups). There were also no significant differences between treatment groups in plasma glucose (p = 0.60) and insulin (p = 0.41), as well as in LDL-cholesterol (p = 0.90) and triglycerides (p = 0.32). The adjusted geometric mean percent change (95 % confidence interval) in high-sensitivity C-reactive protein was 1.59 % (-15.71, 22.44) in the probiotic group and -1.37 % (-18.04, 18.70) in the placebo group (p = 0.82). Gastrointestinal adverse events occurred in 38.5 % and 46.2 % of patients in the probiotic group and placebo group respectively (p = 0.48).

Probiotic supplementation for 12 weeks did not improve glycemic control, lipid or inflammatory markers in patients with type 2 diabetes. Further research is needed to determine the potential benefits and underlying mechanisms of probiotics in subsets of patients.

gov Identifier no. NCT03239366.

Recent evidence underscores a reciprocal relationship between the gut microbiota and prostate cancer (PCa). Dysbiosis, often driven by Western dietary habits and antibiotic use, can heighten systemic inflammation and hinder antitumor immunity, thereby fostering PCa onset and progression. Conversely, certain gut microbes and their metabolites may protect against tumor growth by modulating immune and hormonal pathways that impact therapeutic responses, including androgen deprivation therapy (ADT). Emerging evidence links gut microbial shifts to PCa aggressiveness, potentially sustaining local androgen production and promoting resistance. In this review, we explore current understanding of the gut-PCa interplay, highlighting key knowledge gaps and the need for further research to clarify how targeting the microbiome might influence PCa outcomes.

The mechanistic role of gut microbiota in metabolic dysfunction-associated steatotic liver disease (MASLD) and chronic kidney disease (CKD) is increasingly recognized. Despite their close association, comparative data regarding gut dysbiosis in these disorders are limited. This study included 22 healthy controls and 180 patients (90 MASLD, 60 CKD, and 30 both diseases with sex- and age-matched). Fecal bacterial 16 S ribosomal RNA sequencing and butyryl-CoA: acetate CoA transferase (BCoAT) gene expression were analyzed. Plasma intestinal fatty acid binding protein (I-FABP), representing intestinal barrier dysfunction, was assessed using the ELISA method. Our data showed that alpha and beta diversities of gut microbiota differed between MASLD and healthy controls. However, only beta diversities were different between CKD and healthy individuals. The MASLD and CKD groups displayed fewer SCFA-producing genera, particularly Bifidobacterium, than healthy controls. Fecal BCoAT levels were inversely correlated with eGFR and I-FABP levels. Patients with CKD had significantly enriched pathogenic bacteria, reduced BCoAT, and increased I-FABP levels versus MASLD. Combining significant bacterial genera discriminated MASLD from CKD with high diagnostic accuracy (AUC of 0.90). Among patients with both diseases, gut microbial alterations showed mixed characteristics of MASLD and CKD. These data highlighted the shared and distinct gut dysbiosis and related biomarkers, which could provide a better understanding of MASLD and CKD pathogenesis.

Dysbiosis refers to the disruption of the gut microbiota balance and is the pathological basis of various diseases. The main pathogenic mechanisms include impaired intestinal mucosal barrier function, inflammation activation, immune dysregulation, and metabolic abnormalities. These mechanisms involve dysfunctions in the gut-brain axis, gut-liver axis, and others to cause broader effects. Although the association between diseases caused by dysbiosis has been extensively studied, many questions remain regarding the specific pathogenic mechanisms and treatment strategies. This review begins by examining the causes of gut microbiota dysbiosis and summarizes the potential mechanisms of representative diseases caused by microbiota imbalance. It integrates clinical evidence to explore preventive and therapeutic strategies targeting gut microbiota dysregulation, emphasizing the importance of understanding gut microbiota dysbiosis. Finally, we summarized the development of artificial intelligence (AI) in the gut microbiota research and suggested that it will play a critical role in future studies on gut dysbiosis. The research combining multiomics technologies and AI will further uncover the complex mechanisms of gut microbiota dysbiosis. It will drive the development of personalized treatment strategies.

Bee pollen, a natural honeybee product, is hailed as a treasure trove of human nutrition. Among the nourishing substances of bee pollen, the constituents with a low molecular weight (such as phenolic acids and flavonoid glycosides) have been extensively studied in the past decades, whereas the polysaccharides with a relatively high molecular weight have received much less attention. To deepen our understanding of bee pollen polysaccharides, this review summarizes the published findings related to their preparation technologies, structural characteristics and biological activities. Among the preparation technologies, ultrasonic-assisted extraction is currently the most effective technology for the recovery of polysaccharides from bee pollen, because ultrasound can crack the pollen exine into fragments and facilitate the release of polysaccharides present in the pollen intine. The preliminary structures, including the molecular weight and monosaccharide composition, of bee pollen polysaccharides have been widely reported, but their fine structures have not fully elucidated. Moreover, bee pollen polysaccharides have antioxidant, immunomodulatory, and antitumor activities, exhibiting potential application in functional foods. Furthermore, bee pollen polysaccharides can modulate the composition of gut microbiota and promote the production of short-chain fatty acids. It is expected that this review can provide inspiration for the development and utilization of bee pollen polysaccharides.

In this review, we explore the biomarkers of different psychiatric disorders, such as major depressive disorder, generalized anxiety disorder, schizophrenia, and bipolar disorder. Moreover, we show the interplay between genetic and environmental factors. Novel techniques such as genome-wide association studies (GWASs) have identified numerous risk loci and single-nucleotide polymorphisms (SNPs) implicated in these conditions, contributing to a better understanding of their mechanisms. Moreover, the impact of genetic variations on drug metabolisms, particularly through cytochrome P450 (CYP450) enzymes, highlights the importance of pharmacogenomics in optimizing psychiatric treatment. This review also explores the role of neurotransmitter regulation, immune system interactions, and metabolic pathways in psychiatric disorders. As the technology advances, integrating genetic markers into clinical practice will be crucial in advancing precision psychiatry, improving diagnostic accuracy and therapeutic interventions for individual patients.

Commensal bacteria have been implicated in the modulation of steroid hormones, including circulating androgen levels in the host. However, the microbial genetic pathways involved in androgen production have not been fully characterized. Here we identify a microbial gene encoding an enzyme that catalyses the conversion of androstenedione to epitestosterone in the gut microbiome member Clostridium scindens and named this gene desF. We demonstrate that epitestosterone impacts androgen receptor-dependent prostate cancer cell proliferation in vitro. We also demonstrate that stool desF levels are elevated in patients with prostate cancer who are unresponsive to abiraterone/prednisone therapy. Bacterial isolates from urine or prostatectomy tissue produced androgens, and 17β-hydroxysteroid dehydrogenase activity encoded by the desG gene was detected in strains of the urinary tract bacterium Propionimicrobium lymphophilum. Furthermore, we demonstrate that urinary androgen-producing bacterial strains can promote prostate cancer cell growth through metabolism of cortisol and prednisone. Abiraterone, which targets host desmolase (CYP17A1), a rate-limiting enzyme in adrenal steroidogenesis, does not inhibit bacterial desmolase (DesAB), whereas the conversion of prednisone to androgens by DesAB, DesF and DesG drives androgen-receptor-dependent prostate cancer cell line proliferation in vitro. Our results are a significant advance in steroid microbiology and highlight a potentially important role for gut and urinary tract bacteria in host endocrine function and drug metabolism.

Over the past few decades, there has been a surge in global study on the relationship between gut microbiota and human health. Numerous human illnesses have been linked to dysbiosis. Gram-positive firmicutes and Gram-negative bacteroidetes are the two leading bacterial phyla that make up 90% of the gut microbiome. Many symbionts in the gut environment establish intricate relationships with host defense to stop both local and non-native dangerous bacteria from colonizing and invading. Dysbiosis alters the paracellular route and damages the epithelium, enabling them to penetrate the epithelium and come into contact with the immune cells. Impaired intestinal barrier function, immune regulation mediated by metabolites derived from the gut microbiota, posttranslational modification of host proteins such as increased citrullination, regulation of the gut microbiota's effect on immune cells, intestinal epithelial cell autophagy, interaction between the microbiome and human leukocyte antigen alleles, and interaction with microRNAs are some of the mechanisms involved in rheumatoid arthritis (RA). The gut microbiota, Prevotella copri, and Collinsella spp. were shown to be higher in the early/preclinical phases of RA, while Bacteroidetes, Bifidobacteria, and Eubacterium rectale were found to be lower. Probiotic-based early dietary intervention may reduce inflammation and slow the rate of joint deterioration, and such intervention can also aid in the restoration of gut microbiota equilibrium. This review article describes the gut microbial dysbiosis and role of probiotics in RA.

Everyday actions such as eating, tooth brushing or applying cosmetics inherently modulate our microbiome. Advances in sequencing technologies now facilitate detailed microbial profiling, driving intentional microbiome-targeted product development. Inspired by an academic-industry workshop held in January 2024, this review explores the oral, skin and gut microbiomes, focussing on the potential long-term implications of perturbations. Key challenges in microbiome safety assessment include confounding factors (ecological variability, host influences and external conditions like geography and diet) and biases from experimental measurements and bioinformatics analyses. The taxonomic composition of the microbiome has been associated with both health and disease, and perturbations like regular disruption of the dental biofilm are essential for preventing caries and inflammatory gum disease. However, further research is required to understand the potential long-term impacts of microbiome disturbances, particularly in vulnerable populations including infants. We propose that emerging technologies, such as omics technologies to characterize microbiome functions rather than taxa, leveraging artificial intelligence to interpret clinical study data and in vitro models to characterize and measure host-microbiome interaction endpoints, could all enhance the risk assessments. The workshop emphasized the importance of detailed documentation, transparency and openness in computational models to reduce uncertainties. Harmonisation of methods could help bridge regulatory gaps and streamline safety assessments but should remain flexible enough to allow innovation and technological advancements. Continued scientific collaboration and public engagement are critical for long-term microbiome monitoring, which is essential to advancing safety assessments of microbiome perturbations.

More and more recent studies highlight the crucial role of the human microbiome in maintaining health, while modern advancements in metagenomic sequencing technologies have been accumulating data that are associated with human diseases. Although metagenomic data offer rich, multifaceted information, including taxonomic and functional abundance profiles, their full potential remains underutilized, as most approaches rely only on one type of information to discover and understand their related correlations with respect to disease occurrences. To address this limitation, we propose a multistage fusion tabular transformer architecture (MSFT-Transformer), aiming to effectively integrate various types of high-dimensional tabular information extracted from metagenomic data. Its multistage fusion strategy consists of three modules: a fusion-aware feature extraction module in the early stage to improve the extracted information from inputs, an alignment-enhanced fusion module in the mid stage to enforce the retainment of desired information in cross-modal learning, and an integrated feature decision layer in the late stage to incorporate desired cross-modal information. We conduct extensive experiments to evaluate the performance of MSFT-Transformer over state-of-the-art models on five standard datasets. Our results indicate that MSFT-Transformer provides stable performance gains with reduced computational costs. An ablation study illustrates the contributions of all three models compared with a reference multistage fusion transformer without these novel strategies. The result analysis implies the significant potential of the proposed model in future disease prediction with metagenomic data.

The intestine, as a critical interface between the external environment and the internal body, plays a central role in nutrient absorption, immune regulation, and maintaining homeostasis. The intestinal epithelium, composed of specialized epithelial cells, harbors apical anion transporters that primarily mediate the transport of chloride and bicarbonate ions, essential for maintaining electrolyte balance, pH homeostasis, and fluid absorption/secretion. In addition, the intestine hosts a diverse population of gut microbiota that plays a pivotal role in various physiological processes including nutrient metabolism, immune regulation, and maintenance of intestinal barrier integrity, all of which are critical for host gut homeostasis and health. The anion transporters and gut microbiome are intricately interconnected, where alterations in one can trigger changes in the other, leading to compromised barrier integrity and increasing susceptibility to pathophysiological states including gut inflammation. This review focuses on the interplay of key apical anion transporters including Down-Regulated in Adenoma (DRA, SLC26A3), Putative Anion Transporter-1 (PAT1, SLC26A6), and Cystic Fibrosis Transmembrane Conductance Regulator [CFTR, ATP-binding cassette subfamily C member 7 (ABCC7)] with the gut microbiome, barrier integrity, and their relationship to gut inflammation.

Although several studies have identified a distinct gut microbiota in individuals with acute ischemic stroke (AIS), there is a limited amount of research that has simultaneously investigated alterations in the oral and intestinal microbiota in AIS patients and their correlation with clinical prognosis. This was a prospective and observational single-center cohort study in which we included 160 AIS patients who were admitted within 24 h after a stroke event. We collected oral and rectal swab samples for analysis using 16S rRNA high-throughput sequencing. Our study revealed that patients with unfavorable outcomes after AIS showed early disruptions in their oral and intestinal microbiota. Rectal swabs showed increased levels of facultatively anaerobic bacteria in patients with a poor prognosis, while the oral cavity exhibited higher levels of anaerobic and opportunistic pathogenic bacteria. By employing machine learning analysis, we found that the microbiota composition at both rectal and oral sites could predict early and long-term outcomes. Moreover, patients with a poor prognosis displayed increased oral bacterial colonization in the rectal microbiota and altered interactions between the oral and gut microbiota. This study reveals distinct rectal and oral bacteria that could predict unfavorable outcomes for AIS patients. Monitoring the microbiota of various body sites during the early stages after admission may hold prognostic value and inform personalized treatment strategies. The presence of oral bacteria colonizing the intestines during the acute phase of stroke could serve as an early indication of poor outcomes for AIS patients.

Taolimiao-Alashan Nur (T-A Nur) is an important breeding site for the Relict Gulls (Larus relictus) and many other waterbirds. To understand the gut health status of rare bird species living there and to protect these bird species, this study analyzed the gut microbiota of four waterbird species, including Relict Gull (L. relictus), Black-necked Grebe (Podiceps nigricollis), Greylag Goose (Anser anser), and Ruddy Shelduck (Tadorna ferruginea), using 16S rRNA high-throughput sequencing. Results showed that the gut microbiota of Ruddy Shelduck had the highest α-diversity, while Greylag Goose had the lowest. The composition of gut microbiota varied significantly among the bird species. The dominant bacterial phylum in the guts of Black-necked Grebe, Greylag Goose, and Ruddy Shelduck was Firmicutes, while it was Pseudomonadota in Relict Gull. At the genus level, the dominant bacteria were Halomonas in Black-necked Grebe, Escherichia-Shigella in Relict Gull, Ligilactobacillus in Greylag Goose, and Enterococcus in Ruddy Shelduck. Correlation analysis revealed significant relationships among gut bacterial communities, suggesting that gut bacteria can regulate host metabolism and physiological state by their interactions. KEGG functional predictions indicated that gut microbiota were primarily involved in metabolism. The abundance of metabolism-related microorganisms in Relict Gull was significantly lower than in Greylag Goose and Ruddy Shelduck, indicating that the gut microbiota of Greylag Goose and Ruddy Shelduck can provide stronger metabolic functions for the hosts. Additionally, microorganisms related to human diseases were more abundant in the gut of Relict Gull compared to Ruddy Shelduck and Black-necked Grebe, and in Greylag Goose compared to Ruddy Shelduck. These findings suggested that the gut microbiota of birds in this area harbor some human pathogens, which warrants attention and preventive measures.

Background/Objectives: The aim of this study was to qualitatively and quantitatively assess the bacterial domain of the gut microbiome in elderly patients with type 2 diabetes (T2D), with a focus on sex differences, glycemic control, and lipid disorders. Methods: This study included 60 older adults with T2D (38 women and 22 men) treated with metformin or a combination of metformin and insulin. The gut microbiota was profiled using 16S rRNA gene sequencing. Statistical analyses, including correlation analysis and multiple regression, were performed to identify the associations between microbial taxa, sex, and metabolic parameters. Results: No statistically significant differences in alpha or beta diversity were observed between the sexes. Multiple regression analysis indicated a positive relationship between Tenericutes and HbA1c in male participants (β = 2.22931, CI [0.75, 3.70], R = 0.67; R2 = 0.36; unadjusted p = 0.0052; adjusted p = 0.0496). In female participants, G0' (β = -2.24107, CI [-3.19, -1.30], R = 0.78; R2 = 0.58; unadjusted p = 0.00003; adjusted p = 0.0005) and HbA1c (β = -1.86670, CI [-2.61, -1.12], R = 0.78; R2 = 0.58; unadjusted p = 0.00001; adjusted p = 0.0003) correlated negatively with Verrucomicrobia as well G0' (β = -1.90427, CI [-2.95, -0.85], R = 0.46; R2 = 0.17; unadjusted p = 0.0008; adjusted p = 0.007) and HbA1c (β = -1.69561, CI [-2.52, -0.87], R = 0.46; R2 = 0.17; unadjusted p = 0.0002; adjusted p = 0.002) correlated negatively with OD1 bacteria, known as Parcubacteria. Conclusions: In this elderly population with type 2 diabetes, biological sex did not significantly affect the gut microbiota diversity. However, several exploratory associations between microbial taxa and metabolic parameters differed between men and women, suggesting that sex may influence specific aspects of microbiota-metabolism interactions. These preliminary findings underscore the importance of considering both age- and sex-related factors when investigating the gut microbiome in the context of type 2 diabetes.

The thyroid gland is the body's largest single organ specialized for endocrine hormone production, and still unraveled mechanisms regulate its interaction between the hypothalamic-pituitary-thyroid axis and composition of the gut microbiota: in particular, a disrupted integrity of the intestinal barrier, causing dysbiosis and increasing detrimental substances or reducing beneficial metabolites, such as short-chain fatty acids (SCFAs) with proinflammatory effects, may be crucial for the induction of an autoimmune thyroid disease. More specifically, Lactobacilli and Bifidobacteria have a role in this partnership through a "molecular mimicry" mechanism, as their protein sequences share structural similarity with thyroid peroxidase and thyroglobulin. Lactobacilli can also increase T helper 17 cells, modifying the number of colonic regulatory T cells, largely implicated in the maintenance of immunological tolerance at the gut barrier. Additionally, Blautia and Anaerostipes work beneficially with butyric acid, one of the SCFAs, promoting antimicrobial peptide synthesis from the intestinal cells and bolstering the innate immune system's ability to struggle against pathogens, which can also influence thyroid hormone levels by regulating iodine uptake and metabolism. This review aims to summarize the current knowledge about the contribution of gut microbiota changes in triggering immune abnormalities leading to autoimmune thyroid diseases.

The gut microbiota is a diverse ecosystem that significantly impacts human health and disease. This article focuses on how the gut microbiota interacts with inflammatory bowel diseases and colorectal tumors, especially through immune regulation. The gut microbiota plays a role in immune system development and regulation, while the body's immune status can also affect the composition of the microbiota. These microorganisms exert pathogenic effects or correct disease states in gastrointestinal diseases through the actions of toxins and secretions, inhibition of immune responses, DNA damage, regulation of gene expression, and protein synthesis. The microbiota and its metabolites are essential in the development and progression of inflammatory bowel diseases and colorectal tumors. The complexity and bidirectionality of this connection with tumors and inflammation might render it a new therapeutic target. Hence, we explore therapeutic strategies for the gut microbiota, highlighting the potential of probiotics and fecal microbiota transplantation to restore or adjust the microbial community. Additionally, we address the challenges and future research directions in this area concerning inflammatory bowel diseases and colorectal tumors.

Due to the heterogeneity of the human gut environment, the gut microbiota is complex and diverse, and has been insufficiently explored. In this study, one fresh fecal sample was cultured using 12 commercial or modified media and incubation of culture plates anaerobically and aerobically, the conventional experienced colony picking (ECP) was first used to isolate the colonies and obtain pure culture strains. On this basis, all the colonies grown on the culture plates were collected for culture-enriched metagenomic sequencing (CEMS), and the original sample was also subjected to direct culture-independent metagenomic sequencing (CIMS), the study compared the effects of three methods for analyzing the microbiota contained in the sample. It was found that compared with CEMS, conventional ECP failed to detect a large proportion of strains grown in culture media, resulting in missed detection of culturable microorganisms in the gut. Microbes identified by CEMS and CIMS showed a low degree of overlap (18% of species), whereas species identified by CEMS and CIMS alone accounted for 36.5% and 45.5%, respectively. It suggests that both culture-dependent and culture-independent approaches are essential in revealing gut microbial diversity. Moreover, based on the CEMS results, growth rate index (GRiD) values for various strains on different media were calculated to predict the optimal medium for bacterial growth; this method can be used to design new media for intestinal microbial isolation, promote the recovery of specific microbiota, and obtain new insights into the human microbiome diversity. This is among the first studies on CEMS of the human gut microbiota.

Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. Induction and maintenance of remission is a crucial therapeutic goal. We investigated curcumin's efficacy in treatment of pouchitis.

The double-blind trial included an induction cohort of refractory pouchitis patients and a maintenance cohort of patients without pouchitis after IPAA. Patients received either placebo or curcumin for 8 weeks. The pouchitis activity were assessed before and after and was compared between cohorts or groups. Laboratory inflammation indicators, nutritional status and quality of life were also appraised.

52 patients were included, with 39 and 13 patients entering the maintenance cohort and induction cohort, respectively. In maintenance cohort, the proportion of clinical remission elevated from 11 to 89% in curcumin group (p = 0.005), whereas there was no significant difference in placebo group (10% vs 5%, p = 1).In induction cohort, 67% (4/6) patients achieved clinical response after 8 weeks' intervention of curcumin, whereas none treated with placebo (p = 0.021). Patients treated with curcumin appeared less inflammation and there was no significant difference in indicators changes between two cohorts.

Curcumin has preventive and therapeutic effects on pouchitis. Curcumin supplementation can reduce the disease activity and improve the nutritional status of patients with after IPAA.

ChiCTR, ChiCTR1900022243. Registered 31 March 2019, https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR1900022243.