Horizontal gene transfer (HGT) mediated diversification is a critical force driving evolutionary and ecological processes. However, how HGT might relate to anthropogenic activity such as nitrogen addition, and its subsequent effect on functional diversity and cooccurrence networks remain unknown. Here we approach this knowledge gap by blending bacterial 16S rRNA gene amplicon and shotgun metagenomes from a platform of cessation of nitrogen additions and continuous nitrogen additions. We found that bacterial HGT events, functional genes, and virus diversities increased whereas bacterial taxonomic diversity decreased by nitrogen additions, resulting in a counterintuitive strong negative association between bacterial taxonomic and functional diversities. Nitrogen additions, especially the ceased one, complexified the cooccurrence network by increasing the contribution of vitamin B12 auxotrophic Acidobacteria, indicating cross-feeding. These findings advance our perceptions of the causes and consequences of the diversification process in community ecology.

Bacteriophages (phages), viruses capable of infecting and lysing bacteria, are a promising alternative for treating infections from hypervirulent, antibiotic-resistant pathogens like Klebsiella pneumoniae, though narrow host range and phage resistance remain challenges. In this study, the hypervirulent K. pneumoniae NTUH-K2044 was used to purify phage ΦK2044, while two ΦK2044-resistant strains were used to purify two further phages: ΦKR1, and ΦKR8 from hospital sewage. A detailed characterization showed that ΦK2044 specifically killed KL1 capsule-type K. pneumoniae, while ΦKR1 and ΦKR8 targeted 13 different capsular serotypes. The phage cocktail (ΦK2044 + ΦKR1 + ΦKR8) effectively killed K. pneumoniae in biofilms, pre-treatment biofilm formation, and delayed phage-resistance. The phage cocktail improved 7-day survival in Galleria mellonella and mouse models and showed therapeutic potential in a catheter biofilm model. In summary, this proof-of-principle phage cocktail has a broad host range, including hypervirulent and highly drug-resistant K. pneumoniae, and serves as a promising starting point for optimizing phage therapy.

The "gut-brain axis" is involved in many physiological processes. However, its role in regulating mammary gland (MG) development remains unknown. In this study, we established the mice model of bilateral subdiaphragmatic vagotomy (Vago) to clarify the effects of "gut-brain axis" on MG development in pubertal mice. The results showed that Vago reduced the ratio of Lactobacillus and Bifidobacterium, neuronal excitability in the nucleus of solitary tract (NTS), and synthesis and secretion of BDNF, thereby slowing MG development. Transplanting the gut microbiota of Vago mice to recipient mice replicated these effects, and transplanting the gut microbiota of Control mice to Vago mice did not alleviate these effects. Galacto-Oligosaccharide (GOS), which up-regulates the ratio of Lactobacillus and Bifidobacterium, supplementation elevated NTS neuron excitability, synthesis and secretion of BDNF, and MG development, but Vago reversed these benefits. In conclusion, GOS enhances BDNF-mediated mammary gland development in pubertal mice via the "gut-brain axis".

Rumen microbiotas are known to influence the fat deposition (FD) in sheep, but controversy over causality remains unresolved. Here, we performed microbiome-wide association studies (MWAS), microbiome genome-wide association analysis (mbGWAS) and bidirectional mendelian randomization (MR) analyses on 1,150 sheep with genotype data from whole-genome resequencing, 16S rRNA sequencing and multilevel FD-traits data. We quantified the proportion of individual variation in FD-traits explained by host genetics, rumen microbiota, and their interaction effects. We identified 32 rumen microbiota biomarkers including Bifidobacterium that were associated with FD-traits (P <0.05). Further, utilizing five MR methods, we identified eight causal associations between marker genera and FD-traits (P <0.05), including Butyrivibrio, Olsenella, p-2534-18B5 gut group, Prevotellaceae UCG-003, and Pseudobutyrivibrio causing forward causal effects on FD, and changes in Flexilinea and Suttonella induced by FD. To our knowledge, this is the inaugural attempt to employ MR in sheep to investigate the causal relationships between gastrointestinal microbiota and complex phenotypes, underscoring the potential for developing interventions related to adipose deposition in sheep from the perspective of the rumen microbiome.

Testosterone deficiency can cause abnormal lipid metabolism in men, leading to hyperlipidemia. We identified the testosterone-degrading bacterium Pseudomonas nitroreducens in the fecal samples of male patients with hyperlipidemia. Gastric administration of P. nitroreducens in mice led to testosterone deficiency and elevated blood lipid levels. Whole-genome sequencing of P. nitroreducens revealed the presence of 3/17β-hydroxysteroid dehydrogenase (3/17β-HSD), a gene responsible for testosterone degradation, which is also associated with hyperlipidemia. Microbiota analysis of fecal samples collected from 158 patients with hyperlipidemia and 151 controls revealed that the relative abundance of P. nitroreducens and 3/17β-HSD in the fecal samples of patients with hyperlipidemia was significantly higher than that in controls. These results suggest that P. nitroreducens and 3/17β-HSD may be related to the onset of testosterone deficiency-induced hyperlipidemia. Therefore, treatments targeted at eradicating testosterone-degrading bacteria are a potential future option for patients with testosterone-induced hyperlipidemia and should thus be studied further.

Melatonin (MT) (N-acetyl-5-methoxytryptamine) is an indoleamine recognized primarily for its crucial role in regulating sleep through circadian rhythm modulation in humans and animals. Beyond its association with the pineal gland, it is synthesized in various tissues, functioning as a hormone, tissue factor, autocoid, paracoid, and antioxidant, impacting multiple organ systems, including the gut-brain axis. However, the mechanisms of extra-pineal MT production and its role in microbiota-host interactions remain less understood. This review provides a comprehensive overview of MT, including its production, actions sites, metabolic pathways, and implications for human health. The gastrointestinal tract is highlighted as an additional source of MT, with an examination of its effects on the intestinal microbiota. This review explores whether the microbiota contributes to MT in the intestine, its relationship to food intake, and the implications for human health. Due to its impacts on the intestinal microbiota, MT may be a valuable therapeutic agent for various dysbiosis-associated conditions. Moreover, due to its influence on intestinal MT levels, the microbiota may be a possible therapeutic target for treating health disorders related to circadian rhythm dysregulation.

The composition of bacteria in the human colon has been a subject of interest since the beginning of microbiology. With the development of methods for culturing strict anaerobic bacteria under multiple culture conditions, it was shown the gut contained more than 400 bacterial species and different people harbor different abundant species. The term "gut microbiome" in this review refers to bacteria studied in stool samples. Molecular methods for determining the bacterial composition of human gut has revealed more than 3000 species and less than 130 genera, indicating that the diversity of human colonic bacteria is concentrated at the species and strain levels. This review concludes with a discussion of how diversity can lead to unity of individual holobionts, between holobionts, and between populations. One of the reasons for the unity is that different bacterial species can have similar functional genes.

Environmental osmolarity plays a crucial role in regulating the functions and behaviors of both host cells and pathogens. However, it remains unclear whether and how environmental osmotic stimuli modulate bacterial‒host interfacial adhesion. Using single-cell force spectroscopy, we revealed that the interfacial adhesion force depended nonlinearly on the osmotic prestimulation of host cells but not bacteria. Quantitatively, the adhesion force increased dramatically from 25.98 nN under isotonic conditions to 112.45 or 93.10 nN after the host cells were treated with the hypotonic or hypertonic solution. There was a strong correlation between the adhesion force and the number of host cells harboring adherent/internalized bacteria. We further revealed that enhanced overexpression levels of collagen XV and II were responsible for the increases in interfacial adhesion under hypotonic and hypertonic conditions, respectively. This work provides new opportunities for developing host-directed antibacterial strategies related to interfacial adhesion from a mechanobiological perspective.

The interaction between the gut-microbiota-derived metabolites and brain has long been recognized in both health and disease. The liver, as the primary metabolic organ for nutrients in animals or humans, plays an indispensable role in signal transduction. Therefore, in recent years, Researcher have proposed the Gut-Liver-Brain Axis (GLBA) as a supplement to the Gut-Brain Axis. The GLBA plays a crucial role in numerous physiological and pathological mechanisms through a complex interplay of signaling pathways. However, gaps remain in our knowledge regarding the developmental and functional influences of the GLBA communication pathway. The gut microbial metabolites serve as communication agents between these three distant organs, functioning prominently within the GLBA. In this review, we provide a comprehensive overview of the current understanding of the GLBA, focusing on signaling molecules role in animal and human health and disease. In this review paper elucidate its mechanisms of communication, explore its implications for immune, and energy metabolism in animal and human, and highlight future research directions. Understanding the intricate communication pathways of the GLBA holds promise for creating innovative treatment approaches for a wide range of immune and metabolic conditions.

The rapid development of high-throughput sequencing techniques provides an unprecedented opportunity to generate biological insights into microbiome-related diseases. However, the relationships among microbes, metabolites and human microenvironment are extremely complex, making data analysis challenging. Here, we present NMFGOT, which is a versatile toolkit for the integrative analysis of microbiome and metabolome data from the same samples. NMFGOT is an unsupervised learning framework based on nonnegative matrix factorization with graph regularized optimal transport, where it utilizes the optimal transport plan to measure the probability distance between microbiome samples, which better dealt with the nonlinear high-order interactions among microbial taxa and metabolites. Moreover, it also includes a spatial regularization term to preserve the spatial consistency of samples in the embedding space across different data modalities. We implemented NMFGOT in several multi-omics microbiome datasets from multiple cohorts. The experimental results showed that NMFGOT consistently performed well compared with several recently published multi-omics integrating methods. Moreover, NMFGOT also facilitates downstream biological analysis, including pathway enrichment analysis and disease-specific metabolite-microbe association analysis. Using NMFGOT, we identified the significantly and stable metabolite-microbe associations in GC and ESRD diseases, which improves our understanding for the mechanisms of human complex diseases.

The lower female reproductive tract (FRT) hosts a complex microbial environment, including eukaryotic and prokaryotic viruses (the virome), whose roles in health and disease are not fully understood. This review consolidates findings on FRT virome composition, revealing the presence of various viral families and noting significant gaps in knowledge. Understanding interactions between the virome, microbiome, and immune system will provide novel insights for preventing and managing lower genital tract disorders.

The success of allogeneic hematopoietic cell transplantation (alloHCT) in curing hematologic disorders is limited by its short- and long-term toxicities. One such toxicity is oral mucositis (OM), causing pain, speech/swallowing difficulty, and prolonged hospitalization. Although conditioning chemoradiotherapy is the direct cause of OM, potential host-intrinsic mediators of mucosal injury remain elusive. We hypothesized that the oral microbiota may influence OM severity. We used a validated comprehensive scoring system based on specialized Oral Medicine examinations to longitudinally quantify OM severity in alloHCT recipients. High-throughput multi-site profiling of the oral microbiota was performed in parallel. We identify a sex-dependent commensal bacterium, Oribacterium asaccharolyticum, whose presence in saliva before transplantation is associated with more severe OM 14 days after transplantation. The sex predilection of this species correlated with higher uric acid levels in men. Our findings represent the first sex-dependent microbiota-mediated pathway in OM pathogenesis and introduce novel targets for preventative interventions.

Previous research has established that the formation of Gardnerella vaginalis (GV) biofilm is one of the primary reasons for bacterial vaginosis (BV) recurrence. This study was the first to explore the impact of Streptococcus agalactiae (group B Streptococcus, GBS) on GV biofilm in a co-culture scenario. The results revealed that GBS could significantly increased the GV biomass in 48-hours dual-species biofilms. The luxS gene of GBS was significantly higher in dual-species biofilm, while knockdown of the luxS gene resulted in a significant decrease in mono- and dual-species biofilms. Meanwhile, in vitro addition of AI-2 (product of luxS gene) substantially increased biofilm biomass. Furthermore, we found that the expression of two genes related to biofilm formation was notably elevated in GV after receiving AI-2 signals. Collectively, these findings suggest that GBS enhances GV biofilm formation via luxS/AI-2 in an in vitro co-culture model, which in turn may promotes recurrence of BV.

During the coronavirus disease 2019 (COVID-19) pandemic, the exploration of microecology has been essential for elucidating the intricacies of infection mechanisms and the recovery of afflicted individuals. To decipher the interplay of microorganisms between the intestinal and respiratory tracts, we collected sputum and throat swabs and feces from COVID-19 patients and explored the mutual migration among intestinal and respiratory microorganisms. Using next-generation sequencing (NGS) technology, we investigated intestinal and respiratory microorganism intermigration in two patients with severe COVID-19 during their hospitalization. Notably, we observed an expedited recovery of microecological equilibrium in one patient harboring Mycobacterium avium. Comparative analyses between 32 healthy controls and 110 COVID-19 patients with different disease severities revealed alterations in predominant microorganisms inhabiting the respiratory and intestinal tracts of COVID-19 patients. Among the alterations, intestinal Bacteroides vulgatus (BV) was identified as a noteworthy microorganism that exhibited marked enrichment in patients with severe COVID-19. BV, when highly abundant, may inhibit the transitional growth of Escherichia coli/Enterococcus, indirectly prevent the overgrowth of salivary streptococci, and maintain lung/intestinal microecology stability. In summary, this study elucidates the bidirectional microbial intermigration between the intestinal and respiratory tracts in COVID-19 patients. These findings are expected to provide new ideas for the treatment and management of COVID-19, underscoring the essential role of microecology in infectious diseases. Nevertheless, a systematic study of the roles of BV in recovery from infection is required to gain a deeper understanding of the mechanisms of microbial migration.

An intensive feeding system might improve the production cycle of yaks. However, how intensive feeding system contributes to yak growth is unclear. Here, multi-omics, including rumen metagenomics, rumen and plasma metabolomics, were performed to classify the regulatory mechanisms of intensive feeding system on yaks. Increased growth performance were observed. Rumen metagenomics revealed that Clostridium, Methanobrevibacter, Piromyces and Anaeromyces increased in the intensively fed yaks, contributing to amino acid and carbohydrate metabolism. The grazing yaks had more cellulolytic microbes. These microbiomes were correlated with the pathways of "Alanine aspartate and glutamate metabolism" and "Pyruvate metabolism". Intensive feeding increased methane degradation functions, while grazing yaks had higher methyl metabolites associated with methane production. These rumen microbiomes and their metabolites resulted in changes in plasma metabolome, finally influencing yaks' growth. Thus, an intensive feeding system altered the rumen microbiome and metabolism as well as host metabolism, resulting in improvements of yak growth.

Microbiome restoration using beneficial microorganisms for corals (BMCs) comprise a promising strategy to help corals cope with anthropogenic stressors. However, there is limited knowledge on the uptake of BMCs by nontarget animals, especially sponges. This study explores whether sponges can acquire BMCs upon direct application and whether inoculations affect sponge health. A 4-week field experiment applying BMCs to Stylissa carteri and Callyspongia crassa assessed three conditions: no inoculation, and BMCs inoculation once and thrice a week. BMC-related strains were naturally present in the seawater and the microbiome of S. carteri. These strains were enriched in response to the inoculation only in the S. carteri microbiome. Microbiomes of both sponges were restructured; sponges were visually healthy and efficiently pumped water at the end of the experiment. These results suggest that sponges can be enriched with BMC-related strains, and that BMC application on nearby corals is unlikely to negatively affect sponge health.

Biofilm formation shields Staphylococcus epidermidis from host defense mechanisms, contributing to chronic implant infections. Using wild-type S. epidermidis 1457, a PIA-negative mutant (1457-M10), and an eDNA-negative mutant (1457ΔatlE), this study examined the influence of biofilm matrix components on human monocyte-derived macrophage (hMDM) interactions. The wild-type strain was resistant to phagocytosis and induced an anti-inflammatory response in hMDMs, while both mutants were more susceptible to phagocytosis and triggered a pro-inflammatory response. Removing eDNA from the 1457 biofilm matrix increased hMDM uptake and a pro-inflammatory reaction, whereas adding eDNA to the 1457ΔatlE mutant reduced phagocytosis and promoted an anti-inflammatory response. Inhibiting TLR9 enhanced bacterial uptake and induced a pro-inflammatory response in hMDMs exposed to wild-type S. epidermidis. This study highlights the critical role of eDNA in immune evasion and the central role of TLR9 in modulating macrophage responses, advancing the understanding of implant infections.

This paper is a call to action. By publishing concurrently across journals like an emergency bulletin, we are not merely making a plea for awareness about climate change. Instead, we are demanding immediate, tangible steps that harness the power of microbiology and the expertise of researchers and policymakers to safeguard the planet for future generations.

The intestinal microbiota (IM) plays a role in the severity of alcohol-associated liver disease. Modifying severe alcohol-associated hepatitis (AH) dysbiosis improves liver injury through tryptophan (Trp) metabolites and the aryl hydrocarbon receptor (AhR). However, Trp's effect on the IM in alcohol use disorder (AUD) patients remains unclear. Here, we used an in vitro microbiota modeling system named Minibioreactor arrays (MBRAs). Feces from AUD patients with or without AH were treated with low, normal, or high Trp concentrations, with subsequent treatment with alcohol. Microbiota composition and AhR activity were studied. We showed that microbial communities from donors were maintained in MBRAs. High and low Trp increased the abundance of pathogen Escherichia Shigella. In the absence of alcohol, Trp changed more bacteria in AUD IM compared to AH IM. Normal Trp increased the AhR activity. Overall, maintaining normal Trp levels may prevent dysbiosis in AUD or AH, pending in vivo confirmation.

Trillions of microbes colonize the ungulate gastrointestinal tract, playing a pivotal role in enhancing host nutrient utilization by breaking down cellulose and hemicellulose present in plants. Here, through large-scale metagenomic assembly, we established a catalog of 131,416 metagenome-assembled genomes (MAGs) and 11,175 high-quality species-level genome bins (SGBs) from 17 species of ungulates in China. Our study revealed the convergent evolution of high relative abundances of carbohydrate-active enzymes (CAZymes) in the gut microbiomes of plateau-dwelling ungulates. Notably, two significant factors contribute to this phenotype: structural variations in their gut microbiome genomes, which contain more CAZymes, and the presence of novel gut microbiota species, particularly those in the genus Cryptobacteroides, which are undergoing independent rapid evolution and speciation and have higher gene densities of CAZymes. Furthermore, these enrichment CAZymes in the gut microbiomes are highly enrichment in known metabolic pathways for short-chain fatty acid (SCFA) production. Our findings not only provide a valuable genomic resource for understanding the gut microbiomes of ungulates but also offer fresh insights into the interaction between gut microbiomes and their hosts, as well as the co-adaptation of hosts and their gut microbiomes to their environments.

Candidate phyla radiation (CPR) constitutes a substantial fraction of bacterial diversity, yet their survival strategies and biogeochemical roles in brackish-saline groundwater remain unknown. By reconstructing 399 CPR metagenome-assembled genomes (MAGs) and 2007 non-CPR MAGs, we found that CPR, affiliated with 44 previously proposed phyla and 8 putative novel phyla, played crucial roles in maintaining the microbial stability and complexity in groundwater. Metabolic reconstructions revealed that CPR participated in diverse processes, including carbon, nitrogen, and sulfur cycles. Adaption of CPR to high-salinity conditions could be attributed to abundant genes associated with heat shock proteins, osmoprotectants, and sulfur reduction, as well as their cooperation with Co-CPR (non-CPR bacteria co-occurred with CPR) for metabolic support and resource exchange. Our study enhanced the understanding of CPR biodiversity in high-salinity groundwater, highlighting the collaborative roles of self-adaptive CPR bacteria and their reciprocal partners in coping with salinity stress, maintaining ecological stability, and mediating biogeochemical cycling.