Microbial regulatory strategies such as fecal microbiota transplantation, synthetic microbial communities, genetically engineered microorganisms, phages, and nanomaterials are increasingly being applied for their precise effects on gastrointestinal tract microbiota. This review underscores the need for targeted strategies, discussing mechanisms, advancements, safety, clinical trials, and optimization while highlighting support methods for improving timing, target selection, and monitoring in microbial interventions.
Pain is closely linked to microbes. The microbiota modulates pain perception through three mechanisms: microbiota-derived metabolites, immunoregulation, and direct stimulation on neurons. Therapeutic strategies like probiotics, fecal microbiota transplantation, and dietary changes show significant potential in pain management. Interdisciplinary advancements are accelerating research and clinical applications in this field.
This review explores the mechanisms underlying Clostridium difficile infection (CDI), focusing on the pathogen's life cycle and its pathogenicity within the host. It further explores the interactions between the gut microbiome, gut metabolites, and CDI. Additionally, the review highlights dietary modulation as a promising strategy to restore gut health, highlighting its potential to alter microbiome composition and reduce infection severity.
Archaea exhibit extensive diversity and ubiquitous distribution in sediments across a range of habitats, from terrestrial inland to deep-sea environments, including hot springs, salt lakes, freshwater lakes, rivers, mangroves, estuaries, coastal areas, seafloor sediments, cold seeps, and hydrothermal vents. The archaeal communities in sediments are predominantly composed of Thermoproteota, Halobacteriota, Asgardarchaeota, Thermoplasmatota, and Nanoarchaeota. Archaea play pivotal roles in the carbon, nitrogen, and sulfur cycles within sediments, with metabolic potentials varying across different archaeal lineages.
Intestinal homeostasis is crucial for host health. MicroRNA (miRNA)–microbiota interactions maintain intestinal health by regulating the barrier function, immune response, microbiota composition, and their metabolic activities. These interactions further influence host metabolism, behavior, and cognition. With advancements in sequencing and artificial intelligence, precise identification and manipulation of miRNA–microbiota interactions holds promise for manipulating intestinal homeostasis and promoting health in humans and animals.
The illustration of health benefits of Bifidobacterium animalis subsp. lactis NJ241 isolated from naturally fermented bovine milk. Integrative approaches unraveled that daily supplementation with Bifidobacterium animalis subsp. lactis NJ241 could markedly suppress colitis-linked reproductive disorders through the gut-testis axis. Bifidobacterium animalis subsp. lactis NJ241 may effectively improve gut barrier disorder by increasing the abundance of Akkermansia muciniphila and its metabolite trans-ferulic acid. Subsequently, the expression levels of pro-inflammatory cytokine IL-6 were suppressed in both serum and testicular tissue, which is closely related to the improvement of sperm motility and viability. It unveiled the prospective pharmacological mechanism of fermented milk-derived probiotic Bifidobacterium animalis subsp. lactis NJ241 in promoting reproductive health benefits.
The ProtHyena framework is designed for protein sequence prediction and functional analysis, leveraging extensive pre-training and task-specific fine-tuning. During the pre-training stage, ProtHyena is trained on 14 million sequences from the Pfam database to predict next amino acid residue, using cross-entropy loss to optimize probabilistic outputs for amino acids. The model's architecture incorporates “Hyena Blocks” that consist of specialized components- the Hyena Operator, Feed Forward, and normalization layers—that process sequence embeddings into robust representations. Moving to the fine-tuning stage, ProtHyena is adapted for diverse downstream tasks including fluorescence prediction, stability assessment, viral protein function analysis, and secondary structure prediction. This targeted fine-tuning enables ProtHyena to accurately address varied biological tasks, making it a versatile tool for protein function prediction and enhancing applications dependent on accurate protein analysis.
The common mycorrhizal networks (CMNs) provide a channel for interplant communication, which enables plants of different species to prepare for pathogen infections without direct exposure. The CMNs change the microbial abundance and community structure of the neighboring plants following pathogen infection in the donor plants, which further enhances microbial interaction and network complexity in neighboring plants. This activation may trigger defense responses in the receiver plants against potential pathogens, which enhances the system's ability to resist infections.
This study revealed that microplastics activated the antioxidant defense system and enhanced maize photosynthesis. Metabolomic and transcriptomic analyses showed that biodegradable and conventional microplastics regulated pathways related to secondary metabolite biosynthesis and carbohydrate metabolism. Belowground changes played a key role in mediating maize responses to microplastic stress.
A large cohort of acute pancreatitis patients (n = 600) underwent whole-exome sequencing, which identified a genetic mutation in FCGBP strongly associated with a predisposition of spontaneous intraabdominal hemorrhage. Incorporating the FCGBP mutation as a clinical indicator enhances the assessment for complications and mortality risk in acute pancreatitis, even in the early phase of the disease.
During Mtb infection, the serine/threonine protein phosphatase PstP is secreted into host cells and directly dephosphorylate S189 on the spliceosomal RNA-binding motif protein RBMX. Dephosphorylated RBMX promotes pathological alternative splicing of the immune gene platelet-activating factor acetylhydrolase PLA2G7, leading to an increase in the expression of the exon9-containing transcript (PLA2G7-exon9+). While the host primarily produces the PLA2G7 isoform lacking exon9 under normal/physiological conditions, Mycobacteria challenge disrupts RNA splicing machinery and raises the levels of PLA2G7-exon9+, thus influencing immune processes.
Fumigation significantly impacts soil nitrogen dynamics and above-ground nutrient metabolism in plants by altering microbial community structure and nitrogen forms. This process increases ammonium nitrogen while reducing nitrate nitrogen levels in plant tissues, a shift driven by the suppression of ammonium-oxidizing microbes and the promotion of denitrifying microbes in soil. Such microbial community changes disrupt the soil nitrogen balance, influencing the availability and distribution of nitrogen to plants. The altered nitrogen profile in subsurface soil subsequently modulates the activities of key metabolic enzymes and the expression of nitrogen transporter genes in above-ground tissues, highlighting the role of soil microorganisms in regulating nutrient turnover and above-ground nutrient metabolism.
This study explores gut microbiota dynamics and metabolic signatures in obesity-prone (OP) and obesity-resistant (OR) mice. Longibaculum and Kineothrix were identified as keystone bacteria in the gut microbiota dynamics of OP and OR mice, respectively. Notably, bacteria such as Kineothrix and Intestinimonas observed in OR mice were also detected in obesity-resistant humans, suggesting cross-species relevance. Metabolomic analysis revealed that ten non-12-OH bile acids, including ursodeoxycholic acid (UDCA), were elevated in OR mice, contributing to weight regulation. Additionally, 22 specific amino acid profiles differentiated OP and OR mice, highlighting potential biomarkers for obesity susceptibility. Integrated analyses of the microbiome, metabolome, and colon transcriptome revealed a dynamic interplay among gut microbiota, bile acids, amino acid metabolism, and gut barrier function, providing both theoretical insights and data support for understanding obesity resistance mechanisms.
In this study, we utilized a PCPA-induced insomnia mouse model to investigate the therapeutic effects of Baihe Dihuang Tang (BDT) on sleep disorders. Our findings indicate that BDT treatment effectively reshapes the dysregulated gut microbiota, characterized by a decrease in Acidobacteria and an increase in Fusobacteria and Firmicutes at the phylum level. Additionally, BDT treatment restores the abnormal levels of neurotransmitters in various brain regions and corrects the hormonal imbalances observed in peripheral blood. Behavioral assessments demonstrated marked improvements in locomotion and reduced sleep latency among BDT-treated mice compared to the insomnia model group. These results highlight the potential of BDT as a promising therapeutic agent for insomnia, suggesting that its multifaceted mechanisms may involve the modulation of gut microbiota and restoration of neuroendocrine and serotonin system functions. Overall, our findings provide compelling evidence supporting BDT's role in the management of insomnia, paving the way for further exploration in clinical applications.
To investigate recently horizontally transferred biosynthetic gene clusters (HTBGCs) within individuals from metagenome-assembled genomes (MAGs), we developed a tool named Horizontally Transferred Biosynthetic Gene Clusters Finder (HTBGC-Finder). In an extensive analysis of human gut microbiota, HTBGC-Finder identified 81 potential HTBGCs. Ribosomally synthesized and post-translationally modified peptides (RiPPs) and cyclic-lactone-autoinducer (CLA) BGCs exhibited significantly higher transfer rates compared to non-RiPPs and non-CLA BGCs. Horizontal BGC transfer was detected exclusively within the phyla Bacteroidota (synonym Bacteroidetes) and Bacillota (synonym Firmicutes). Our analysis also revealed cross-phylum transfer events, suggesting a mechanism for rapid evolution within the gut microbiota.
The bacterial pathogen Erwinia amylovora is the causative agent of fire blight, a devastating disease affecting rosaceous plants globally. Pathogenicity tests in immature pears demonstrated E. amylovora discovered in China exhibit different virulences. Through full-genome sequencing and genetic variations assay, Each strain exhibited a chromosome size of approximately 3.8 Mb, with distinct distribution patterns in plasmids. The genomes of all sequenced strains were compared to the model strain CFBP1430. Single-nucleotide polymorphisms (SNPs) and short deletions, insertions, and other polymorphisms (DIPs) were identified and shared SNPs and DIPs among strains suggest genomic homogeneity, with a higher level of specificity in DIPs. Phylogenetic analysis inferred that the primary pathway of fire blight spread to China followed a trajectory from the Middle East to Central Asia, ultimately reaching Xinjiang.
Molting is a crucial process for crab growth and development. However, the impacts of molting on the structure and function of the gut bacterial community in swimming crab Portunus trituberculatus are poorly understood. Then, dynamic changes in the microbiotas of gut segments (foregut, midgut, and hindgut) after molting were investigated using 16S rRNA gene amplicon and shotgun metagenomic sequencing. We highlight the segment-specific responses in bacterial community compositions, alpha-diversity, and co-occurrence patterns, emphasizing the significant impact of hindgut bacteria on the analysis of the whole gut. The identification of enriched and emerged species and their source, coupled with insights into functional stability and multifunctionality, adds granularity to our understanding of postmolt microbial ecology. We offer potential keys to driving microbial community succession. These findings provide essential insights into the stability and dynamics of gut microbiota, which are crucial for both ecological understanding and sustainable management of crab probiotic regulation.
The Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) diet has been related to a lower risk of dementia and better cognitive function. This study identified 47 circulating metabolites associated with the alternate MIND diet score (aMIND) in the UK Biobank (45,906 participants, 168 metabolites measured) and Whitehall II (6193 participants, 152 metabolites measured). Unsaturated fatty acids showed the strongest positive associations with the aMIND, and very low-density lipoprotein measures and glycoprotein acetyls showed the strongest inverse associations. We constructed a metabolomic signature score (MIND-MetS) to objectively reflect MIND diet adherence. Both aMIND and MIND-MetS were associated with better cognitive outcomes in participants aged 55 years or older, and the MIND-MetS partially mediated the aMIND-cognition associations. In summary, the rapid and widely accessible nuclear magnetic resonance-based metabolomic measure could objectively reflect MIND diet adherence. Moreover, our findings offered insights into the intricate connections among diet, metabolism, and cognition.
The gut microbiota influences host health, with outer membrane vesicles (OMVs) facilitating intercellular communication and transporting bioactive molecules. At high altitudes, OMVs can cross the intestinal barrier, affecting heart function and potentially modulating inflammation, oxidative stress, and apoptosis in cardiomyocytes. Genetic engineering of OMVs may improve their therapeutic efficacy by altering surface properties to enhance targeting and residence time. They could also act as disease biomarker carriers for early detection and monitoring.
The human-derived probiotic Lactobacillus rhamnosus GG (LGG) improves intestinal health in humans. However, in zebrafish, the SpaC pilin of LGG and the LPS produced by SpaC-induced dysbiotic gut microbiota cause intestinal pyroptosis and epithelial damage. This negative effect is host-specific, raising concerns about the safety of using classical terrestrial-derived probiotics strains in aquatic species. These results emphasize the need for species-specific probiotic evaluations and promote the regulation of non-host origin probiotics in aquaculture. Further research is needed to understand the action mechanisms of non-host probiotics and their impacts on economical fish species.