Bacteroides is a crucial mucosal symbiotic bacterium in mammals, with Bacteroides thetaiotaomicron (B. thetaiotaomicron) being particularly noteworthy as a glyco-specialist due to its significant nutritional impact. However, B. thetaiotaomicron may affect host health, but related research is limited.

Our main focus is to understand the patterns of microbial community changes and the molecular mechanisms mediated by microbial metabolites in the alleviation of piglet diarrhea by B. thetaiotaomicron.

Cold stress was induced in piglets to trigger stress-induced diarrhea. The control group and B group were administered a blank medium and 1 × 108 CFU of B. thetaiotaomicron, respectively, on days 1, 3, and 5. The diarrhea rate and growth performance of the piglets were recorded during the experimental period. Based on 16S rRNA gene amplicon sequencing, microbial network analysis, and metabolomics analysis, the composition and changes of the colonic microbiota and metabolites were analyzed. The antibacterial capacity and anti-inflammatory molecular mechanisms of B. thetaiotaomicron metabolites were analyzed through in vitro antibacterial assays and inflammatory cell models.

B. thetaiotaomicron alleviated diarrhea in piglets and improved their growth performance. It influenced the composition of the intestinal microbiota and microbial interactions, with metabolites primarily enriched in the tryptophan metabolism pathway, particularly indole and its derivatives, which were closely related to host phenotypes. In vitro co-culture experiments demonstrated that B. thetaiotaomicron metabolites inhibited the growth of pathogenic bacteria. Further in vitro experiments revealed that these metabolites, including indole, reinforced barrier function and reduced TNF-α-induced inflammation and apoptosis in Caco-2 cells, confirming the significance of the AHR-Nrf2 pathway in mediating these positive effects.

In conclusion, this study offers a theoretical framework for understanding the role of the symbiotic bacterium B. thetaiotaomicron in the gut microbiota ecosystem during diarrhea and its interactions with the host's intestinal tract.

Oncolytic viruses (OVs) hold promise for cancer treatment. However, the antitumor efficacy is limited. Microbiota plays a pivotal role in cancer treatment and its impact on oncolytic virotherapy is unknown. Here, we show that VSVΔ51 has higher antitumor efficacy for hepatocellular carcinoma in the absence of microbiota in female mouse models. VSVΔ51 infection causes microbiota dysbiosis, increasing most of the gut bacteria abundance, while decreasing the commensal Lactobacillus. VSVΔ51 reduced intestinal expression of SLC20A1 that binds to Lactobacillus acidophilus (L. acidophilus) CdpA cell wall protein through IL6-JAK-STAT3 signaling, thereby attenuating attachment and colonization of L. acidophilus. L. acidophilus supplementation confers sensitivity to VSVΔ51 through restoring gut barrier integrity and microbiota homeostasis destroyed by VSVΔ51. In this work, we show that targeting microbiota homostasis holds substantial potential in improving therapeutic outcomes of oncolytic virotherapy.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.

Helicobacter pylori (H. pylori) infection presents increasing challenges to antibiotic therapies owing to limited drug bioavailability, multi-drug resistance and collateral damage to commensal intestinal microflora. To address these problems, here, an ingestible magnetically controlled light-emitting diode (LED) light source was designed for an ingestible capsule to perform antimicrobial photodynamic therapy (aPDT) without an exogenous photosensitizer (ex-PS) at 630 nm. Specifically, we first optimized the antibacterial rates of aPDT with ex-PS and aPDT without ex-PS against H. pylori at the bacterial suspension level by varying the wavelength (405, 530, 630 nm), photosensitizer concentration (2, 4, 6, 8, 10 μg/mL), power density (15, 30 mW/cm2), and energy density (0, 3.6, 7.2, 10.8, 14.4, 18.0 J/cm2). Then, we compared the antibacterial effect of aPDT with ex-PS and aPDT without ex-PS against H. pylori at the biofilm level, revealing that the antibacterial rate of aPDT without ex-PS reached approximately 97 % at 405 nm and 18 J/cm2, similar to that of aPDT with ex-PS under the same conditions. Furthermore, 80 SD rats infected with H. pylori were treated with aPDT with ex-PS and aPDT without ex-PS at the above wavelengths. Histopathological analysis of rat gastrointestinal tissues revealed that aPDT with ex-PS and aPDT without ex-PS exhibited significant antibacterial activity against H. pylori, without side effects on normal tissues. Additionally, aPDT without ex-PS at 630 nm induced an anti-inflammatory response and regulated the intestinal flora. Ultimately, we developed a magnetically controlled LED capsule for in vivo aPDT without ex-PS at 630 nm against H. pylori.

Gut microbiota plays an important role in gut health, and its dysbiosis is closely related to the pathogenesis of various intestinal diseases. The field of gut microbiota and intestinal diseases has not yet been systematically quantified through bibliometric methods. This study conducted bibliometric analysis to delineate the evolution of research on gut microbiota and intestinal diseases. Data were sourced from the Web of Science Core Collection database from 2009 to 2023 and were scientometrically analyzed using CiteSpace. We have found that the number of annual publications has been steadily increasing and showing an upward trend. China and the Chinese Academy of Sciences are the country and institution with the most contributions, respectively. Frontiers in Microbiology and Nutrients are the journals with the most publications, while Plos One and Nature are the journals with the most citations. The field has shifted from focusing on traditional descriptive analysis of gut microbiota composition to exploring the causal relationship between gut microbiota and intestinal diseases. The research hotspots and trends mainly include the correlation between specific intestinal diseases and gut microbiota diversity, the mechanism of gut microbiota involvement in intestinal diseases, the exploration of important gut microbiota related to intestinal diseases, and the relationship between gut microbiota and human gut health. This study provides a comprehensive knowledge map of gut microbiota and intestinal diseases, highlights key research areas, and outlines potential future directions.

Breast cancer is the most commonly diagnosed cancer in women worldwide, with alcohol consumption recognized as a significant risk factor. While epidemiological studies consistently show a positive correlation between alcohol consumption and increased breast cancer risk, the underlying mechanisms remain unclear. Recent evidence suggests that the gut microbiome-the diverse collection of microorganisms, including bacteria, viruses, and fungi, residing in the gastrointestinal tract-plays a pivotal role in systemic health and disease. This is achieved through its regulation of key physiological processes such as metabolism, immune function, and inflammatory responses. Disruption of the gut microbiome (dysbiosis) has recently been implicated in the development of breast cancer. We hypothesized that alcohol exposure induces gut dysbiosis, which in turn drives systemic inflammation and carcinogenic processes. Previously, we demonstrated that alcohol exposure promotes mammary tumor growth and aggressiveness in MMTV-Wnt1 (Wnt1) transgenic mice, an established model for investigating mechanisms of alcohol-induced tumor promotion. In this study, we sought to determine whether alcohol exposure induces gut dysbiosis in adolescent and adult Wnt1 transgenic mice and their wild-type FVB counterparts. Our findings revealed that alcohol exposure significantly reduced microbiome richness in adult Wnt1 and FVB mice. Alcohol exposure also markedly altered microbiome composition in adolescents and adults in both strains. Additionally, we identified specific microbial taxa that were significantly affected by alcohol exposure. These results demonstrate that alcohol disrupts the gut microbiome in a preclinical breast cancer model, providing insights into the potential role of gut dysbiosis in alcohol-induced mammary tumor promotion and offering avenues for future research.

This study aimed to investigate the role of the gut-lung microbiome axis in airway inflammation in asthma and to evaluate the effect of azithromycin on this axis, with a focus on the potential mechanism by which azithromycin reduces allergic airway inflammation.

Haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were used to assess pathological changes in the lung tissues of asthmatic mice. Leukocyte cell types in bronchoalveolar lavage fluid (BALF) samples were quantified following Wright-Giemsa staining. Total IgE, OVA-specific IgE, IL-4, IL-6, and IL-17A levels in BALF and total IgE in serum were measured by ELISA. The respiratory and gut microbiota were analysed using 16S rRNA gene sequencing and subsequent taxonomic analysis.

OVA-challenged asthmatic mice with gut microbiota dysbiosis exhibited alterations in the respiratory microbiota, resulting in further aggravation of airway inflammation. Following faecal microbiota transplantation (FMT) to restore gut microbiota, respiratory microbiota dysbiosis was partially improved, and airway inflammation was significantly alleviated. Furthermore, azithromycin reduced airway inflammation in asthmatic mice, particularly non-eosinophilic inflammation, for which low-dose azithromycin combined with budesonide proved more effective. Azithromycin significantly enhanced the diversity and microbial composition of the gut microbiota and also affected the respiratory microbiota. At the phylum level, azithromycin decreased the abundance of Proteobacteria in the gut microbiota. At the genus level, azithromycin reduced the abundance of Pseudomonas in the respiratory microbiota.

The gut-lung microbiome axis plays a crucial role in airway inflammation in asthma. Azithromycin may reduce airway inflammation in asthma through modulation of the gut-lung microbiome axis.

The ocular surface microbiota plays a critical role in maintaining corneal homeostasis, but its disruption and subsequent effects on corneal functions remain poorly understood. This study investigates how antibiotic-induced microbial depletion affects the corneal circadian transcriptome in C57BL/6J mice. Dysbiosis was induced using a topical antibiotic cocktail, and RNA sequencing was employed to analyze gene expression across eight time points over 24 h. Antibiotic treatment disrupted corneal circadian rhythms, eliminating rhythmicity in 1,812 genes and introducing rhythmicity in 1,928 previously arrhythmic genes. Furthermore, epithelial adhesion was impaired, inflammation was elevated, and neural sensitivity was reduced. More than 50 % of ocular microbial genera exhibited daily oscillations, with six genera showing significant correlations with corneal rhythmic transcripts. Additionally, the administration of TLR agonists restored circadian gene expression patterns, with partial recovery of corneal barrier function and immune homeostasis, further highlighting the potential of microbiota-targeted therapies in treating ocular surface disorders. These findings underscore the critical role of the ocular microbiota in regulating corneal health and suggest that restoring microbial balance via TLR activation may offer new therapeutic avenues for eye diseases.

Donkeys, as single-stomach herbivores, have a complex and diverse microbial community in their digestive tracts. The intestinal bacterial community is crucial for maintaining intestinal homeostasis, as well as the host's overall nutrition and health. However, research on donkey gut microbes is relatively limited, particularly regarding the microbial colonization patterns in different intestinal segments of adult donkeys. Therefore, this study examined the abundance and function of microbiota across various sites of the intestinal tract (duodenum, jejunum, ileum, cecum, colon) and feces of healthy adult Dezhou male donkeys using 16S rRNA gene sequencing and PICRUSt analysis. The results indicate that donkeys have a rich gut microbial diversity and a large microbial population. No significant differences in the indices of alpha diversity were observed among the donkey's duodenum, jejunum, ileum, cecum, colon, and feces. A Venn diagram analysis revealed the presence of both unique (Duodenum: 4645; Jejunum: 3586; Ileum: 4904; Cecum: 4253; Colon: 6135; Feces: 4885) and shared (339) ASVs among the different sections. A principal coordinate analysis (PCoA) revealed significant differences (R2 = 0.2076, p < 0.007) across the six intestinal segments of the donkeys. At the phylum level, Firmicutes (63.64%), Bacteroidetes (20.72%), Verrucomicrobiota (9.16%), Patescibacteria (1.95%), Spirochaetota (1.87%), Actinobacteriota (1.13%), and Proteobacteria (0.42%) were the dominant bacteria in all samples. The Wilcoxon rank-sum test revealed significant differences in the proportions of genera among different intestinal segments. Specific genera were significantly enriched in various segments: Lachnospiraceae_UCG-008 and Sphaerochaeta in the duodenum; Christensenellaceae_R-7_group and Bacillus in the jejunum; NK4A214_group and Alloprevotella in the ileum; UCG-005 and Lactobacillus in the cecum; Clostridium_sensu_stricto_1 and Chlamydia in the colon; and Rikenellaceae_RC9_gut_group and Prevotellaceae_UCG-004 in the feces. A PICRUSt2 functional prediction analysis indicated that carbohydrate metabolism, prokaryotic cellular communities, antimicrobial drug resistance, immune diseases, membrane transport, signal transduction, and transcription exhibited significant differences among the different intestinal segments. This study provided critical primary data on the differences in donkey gut microbiota and the synergistic effects between gut microbiota and host functions. These findings can be used to assess donkey health status, improve breeding, and develop microbial additives.

Little is known about how zoonotic virus infections manifest in wildlife reservoirs. However, a common health consequence of enteric virus infections is gastrointestinal diseases following a shift in gut microbial composition. The sub-Saharan hipposiderid bat complex has recently emerged to host at least three coronaviruses (CoVs), with Hipposideros caffer D appearing particularly susceptible to Hibecovirus CoV-2B infection. In this study, we complement body condition and infection status data with information about the gut microbial community to understand the health impact of CoV infections in a wild bat population. Of the three CoVs, only infections with the distantly SARS-related Hibecovirus CoV-2B were associated with lower body condition and altered the gut microbial diversity and composition. The gut microbial community of infected bats became progressively less diverse and more dissimilar with infection intensity, arguing for dysbiosis as per the Anna Karenina principle. Putatively beneficial bacteria, such as Alistipes and Christensenella, decreased with infection intensity, while potentially pathogenic bacteria, namely Mycoplasma and Staphylococcus, increased. Infections with enterically replicating viruses may therefore cause changes in body condition and gut dysbiosis with potential negative health consequences even in virus reservoirs. We argue that high-resolution data on multiple health markers, ideally including microbiome information, will provide a more nuanced picture of bat disease ecology.

Coccidiosis, caused by different species of Eimeria parasites, is an economically important disease in poultry and livestock worldwide. This study aimed to investigate the changes in the ileal microbiota and fecal metabolites in chickens after repeated infections with low-dose E. mitis. The chickens developed solid immunity against a high dose of E. mitis infection after repeated infections with low-dose E. mitis. The composition of the ileal microbiota and the metabonomics of the Eimeria-immunized group and the control group were detected using 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS). The relative abundance of Neisseria, Erysipelotrichaceae, Incertae sedis, Coprobacter, Capnocytophaga, Bifidobacterium, and the Ruminococcus torques group declined in the Eimeria-immunized chickens, whereas Alloprevotella, Staphylococcus, Haemophilus, and Streptococcus increased. Furthermore, 286 differential metabolites (including N-undecylbenzenesulfonic acid, 1,25-dihydroxyvitamin D3, gluconic acid, isoleucylproline, proline, and 1-kestose) and 19 significantly altered metabolic pathways (including galactose metabolism, ABC transporters, starch and sucrose metabolism, the ErbB signaling pathway, and the MAPK signaling pathway) were identified between the Eimeria-immunized group and the control group. These discoveries will help us learn more about the composition and dynamics of the gut microbiota as well as the metabolic changes in chickens infected with Eimeria spp.

There is a huge quantity of microorganisms in the gut of fish, which exert pivotal roles in maintaining host intestinal and general health. The fish immunity can sense and shape the intestinal microbiota and maintain the intestinal homeostasis. In the meantime, the intestinal commensal microbes regulate the fish immunity, control the extravagant proliferation of pathogenic microorganisms, and ensure the intestinal health of the host. This review summarizes developments and progress on the known interactions between host immunity and intestinal microorganisms in fish, focusing on the recent advances in zebrafish (Danio rerio) showing the host immunity senses and shapes intestinal microbiota, and intestinal microorganisms tune host immunity. This review will offer theoretical references for the development, application, and commercialization of intestinal functional microorganisms in fish. KEY POINTS: • The interactions between the intestinal microorganisms and host immunity in zebrafish • Fish immunity senses and shapes the microbiota • Intestinal microbes tune host immunity in fish.

A central goal of biological anthropology is connecting environmental variation to differences in host physiology, biology, health, and evolution. The microbiome represents a valuable pathway for studying how variation in host environments impacts health outcomes. While there are many resources for learning about methods related to microbiome sample collection, laboratory analyses, and genetic sequencing, there are fewer dedicated to helping researchers navigate the dense portfolio of bioinformatics and statistical approaches for analyzing microbiome data. Those that do exist are rarely related to questions in biological anthropology and instead are often focused on human biomedicine. To address this gap, we expand on existing tutorials and provide a "road map" to aid biological anthropologists in understanding, selecting, and deploying the data analysis and visualization methods that are most appropriate for their specific research questions. Leveraging an existing dataset of fecal samples and survey data collected from wild geladas living in Simien Mountains National Park in Ethiopia (Baniel et al., 2021), this paper guides researchers toward answering three questions related to variation in the gut microbiome across host and environmental factors. By providing explanations, examples, and a reproducible workflow for different analytic methods, we move beyond the theoretical benefits of considering the microbiome within anthropological research and instead present researchers with a guide for applying microbiome science to their work. This paper makes microbiome science more accessible to biological anthropologists and paves the way for continued research into the microbiome's role in the ecology, evolution, and health of human and non-human primates.

The gut microbiome impacts many physiological processes that greatly influence host health and disease. Metabolites produced by the gut microbiota have emerged as central players in regulating these biological pathways, often through the engagement of specific host receptors. Despite the importance of these microbial metabolites and receptors in human biology, the vast majority of these interactions remain uncharted due to the complex nature of the gut microbiome and the multitude of metabolites that these microbes produce. Here, we highlight recent developments in identifying such host-gut microbiota interactions, including characterization of bioactive metabolites and their mechanisms of action. Understanding these pathways will enable the development of prophylactics and therapeutics for treating many inflammatory diseases that are impacted by the gut microbiota.

The intratumoral microbiome (ITM) is in the spotlight due to its possible contribution to the initiation, progression, and invasion of a wide range of cancers. Its precise contribution to cancer tumorigenesis is still elusive, though. Thyroid cancer(TC), the ninth leading cause of cancer globally and the most prevalent endocrine malignancy with a rapidly rising incidence among all cancers, has attracted much attention nowadays. Still, the association between the tumor's microbiome and TC progression and development is an evolving area of investigation with significant consequences for disease understanding and intervention. Therefore, this review offers an appropriate perspective on this emerging concept in TC based on prior studies on the ITM among the most common tumors worldwide, concentrating on TC. Moreover, information on the origin of the ITM and practical methods can pave the way for researchers to opt for the most appropriate method for further investigations on the ITM more accurately.

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.

Studies have shown that gut microbiota (GM) and its metabolites, short-chain fatty acids (SCFAs), are associated with the development of postmenopausal osteoporosis (PMO). This study explored the clinical and laboratory evidence of the relationship of GM and SCFAs to PMO and attempted to determine the potential mechanism of action. 18 patients (Collected from the First Affiliated Hospital of Guangdong Pharmaceutical University between January 2021 and August 2021) were included in this retrospective study, including 10 PMO women and 8 healthy young women as the healthy control (HC) group from Guangzhou, China. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry. The composition of GM and its metabolites, SCFAs, in the fecal samples were measured by 16S rRNA gene sequencing and gas chromatography/mass spectrometry analysis, respectively. Compared with healthy control, PMO group had significantly decreased BMD in lumbar spines 1-4 (BMD_L) and femoral neck (BMD_F). 16S rRNA gene sequencing revealed that, compared with healthy control, PMO group had a markedly decreased abundance in Subdoligranulum, Norank_f_Muribaculaceae, and Alistipes at the genus level. Gas chromatography/mass spectrometry analysis indicated that the concentration of propanoic acid significantly dropped in PMO group. Additionally, we found that Subdoligranulum, Norank_f_Muribaculaceae, and Alistipes were positively correlated with BMD_L. Subdoligranulum and Norank_f_Muribaculaceae were also positively correlated BMD_F and propanoic acid, while Subdoligranulum is the only species that presented a strong correlation with the levels of acetic acid and butyric acid. Our findings indicated that, in postmenopausal women, there were evident changes in GM and SCFAs, and these changes were found correlated with patients' BMD. These correlations provide novel insights into the underlying mechanism of PMO development, representative of early diagnostic markers and therapeutic targets that may improve the bone health in postmenopausal women.

The gut microbiota, a diverse collection of microorganisms in the gastrointestinal tract, plays a critical role in regulating metabolic, immune, and cognitive functions. Disruptions in the composition of these microbial communities, termed dysbiosis, have been linked to various neurodegenerative diseases (NDs), such as Parkinson's disease (PD) and Alzheimer's disease (AD). One of the key pathological features of NDs is neuroinflammation, which involves the activation of microglia and peripheral immune cells. The gut microbiota modulates immune responses through the production of metabolites and interactions with immune cells, influencing the inflammatory processes within the central nervous system. This review explores the impact of gut dysbiosis on neuroinflammation, focusing on the roles of microglia, immune cells, and potential therapeutic strategies targeting the gut microbiota to alleviate neuroinflammatory processes in NDs.

Commensal microbiota is crucial for nutrient digestion and production of biologically active molecules, many of which mimic endogenous ligands of human GPCRs. Bacteroides spp. are among the most abundant bacteria residing in the human gut and their absence has been positively correlated with metabolic disorders. In the present study, we focused on N-acylated glycines (NAGlys) as products of Bacteroides spp. and potential GPCR ligands modulating GLP-1 secretion. Representative strains of the most abundant commensal Bacteroides were cultured in either yeast- or animal-based nutrient broths. The broths post-culture were investigated in terms of the contents of NAGlys and stimulatory effects towards GLP-1 production in GLUTag and NCI-H716 cell lines. Pure preparations of the detected NAGlys were further studied to evaluate stimulation of GLP-1 production and related cellular signalling evoked. The most potent NAGlys were also tested as ligands of key lipid GPCRs involved in the regulation of carbohydrate metabolism: GPR40/FFAR1, GPR55, GPR119, and GPR120/FFAR4. We found that Bacteroides potentiate GLP-1 production, depending on the strain and provided nutrient mix. Long-chain unsaturated oleoyl and arachidonoyl glycines, produced by B. thetaiotaomicron and B. intestinalis in the animal-based broth, were particularly effective in stimulation of GLP-1 secretion. They served as agonists of all the receptors under study expressed in GLP-1-producing cells. The obtained results broaden the knowledge of microbial signalling molecules and their role in regulation of carbohydrate homeostasis. They also emphasise the importance of balanced diet as a source of building blocks for commensal bacteria to produce efficient agonists of lipid GPCRs.

Weak organic acids are commonly found in host niches colonized by bacteria, and they can inhibit bacterial growth as the environment becomes acidic. This inhibition is often attributed to the toxicity resulting from the accumulation of high concentrations of organic anions in the cytosol, which disrupts cellular homeostasis. However, the precise cellular targets that organic anions poison and the mechanisms used to counter organic anion intoxication in bacteria have not been elucidated. Here, we utilize acetic acid, a weak organic acid abundantly found in the gut to investigate its impact on the growth of Staphylococcus aureus. We demonstrate that acetate anions bind to and inhibit d-alanyl-d-alanine ligase (Ddl) activity in S. aureus. Ddl inhibition reduces intracellular d-alanyl-d-alanine (d-Ala-d-Ala) levels, compromising staphylococcal peptidoglycan cross-linking and cell wall integrity. To overcome the effects of acetate-mediated Ddl inhibition, S. aureus maintains a substantial intracellular d-Ala pool through alanine racemase (Alr1) activity and additionally limits the flux of d-Ala to d-glutamate by controlling d-alanine aminotransferase (Dat) activity. Surprisingly, the modus operandi of acetate intoxication in S. aureus is common to multiple biologically relevant weak organic acids indicating that Ddl is a conserved target of small organic anions. These findings suggest that S. aureus may have evolved to maintain high intracellular d-Ala concentrations, partly to counter organic anion intoxication.

Cardiovascular diseases (CVDs) represent a significant global health challenge, underscoring the need for innovative approaches to prevention and treatment. Recent years have seen a surge in interest in unraveling the complex relationship between the gut microbiome and cardiovascular health. This article delves into current research on the composition, diversity, and impact of the gut microbiome on CVD development. Recent advancements have elucidated the profound influence of the gut microbiome on disease progression, particularly through key mediators like Trimethylamine-N-oxide (TMAO) and other microbial metabolites. Understanding these mechanisms reveals promising therapeutic targets, including interventions aimed at modulating the gut microbiome's interaction with the immune system and its contribution to endothelial dysfunction. Harnessing this understanding, personalized medicine strategies tailored to individuals' gut microbiome profiles offer innovative avenues for reducing cardiovascular risk. As research in this field continues to evolve, there is vast potential for transformative advancements in cardiovascular medicine, paving the way for precision prevention and treatment strategies to address this global health challenge.

Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant-derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan-Oxidized Dextran (CMCS-OD) hydrogel formed via dynamic chemical bonds exhibited self-healing capabilities and pH-responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis-induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis-induced bone destruction.

Studies on the immune-regulatory roles played by the commensal microbes residing in the nasal mucosa consider the contribution of antiviral immune responses. Here, we sought to identify the nasal microbiome, Staphylococcus epidermidis-regulated antiviral immune responses and the alteration of polyamine metabolites in nasal epithelium. We found that polyamines were required for the life cycle of influenza A virus (IAV) and depletion of polyamines disturbed IAV replication in normal human nasal epithelial (NHNE) cells. Inoculation of S. epidermidis also suppressed IAV infection and the concentration of polyamines including putrescine, spermidine, and spermine was completely attenuated in S. epidermidis-inoculated NHNE cells. S. epidermidis activated the enzyme involved in the production of ornithine from arginine and downregulated the activity of the enzyme involved in the production of putrescine from ornithine in nasal epithelium. S. epidermidis also induced the activation of enzymes that promote the extracellular export of spermine and spermidine in NHNE cells. Our findings demonstrate that S. epidermidis is shown to be able of creating an intracellular environment lacking polyamines in the nasal epithelium and promote the balance of cellular polyamines in favor of the host to restrict influenza virus replication.

Numerous studies have investigated the relationship between gut microbiota (GM) and multiple sclerosis(MS), highlighting the significant role of GM in MS. However, there is a lack of systematic Scientometric analyses published in this specific research area to provide an overall understanding of the current research status.

Perform a scientometric analysis on research conducted between 2010 and 2023 concerning the link between GM and MS using quantitative and visual analysis software (CiteSpace and VOSviewer.).

From January 1, 2010, and December 31, 2023, a total of 1019 records about GM and MS were retrieved. The number of publications exhibited a consistent upward trend annually. The United States led in publications, showed the strongest level of collaboration among countries. The University of California, San Francisco stands as the top institution in terms of output, and the most prolific and cited authors were Lloyd H. Kasper and Javier Ochoa-Reparaz from the USA. The research in this field primarily centers on investigating the alterations and associations of GM in MS or EAE, the molecular immunological mechanisms, and the potential of GM-based interventions to provide beneficial effects in MS or EAE. The Keywords co-occurrence network reveals five primary research directions in this field. The most frequently occurring keywords are inflammation, probiotics, diet, dysbiosis, and tryptophan. In recent years, neurodegeneration and neuropsychiatric disorders have been prominent, indicating that the investigation of the mechanisms and practical applications of GM in MS has emerged as a current research focus. Moreover, GM research is progressively extending into the realm of neurodegenerative and psychiatric diseases, potentially becoming future research hotspots.

This study revealed a data-driven systematic comprehension of research in the field of GM in MS over the past 13 years, highlighted noteworthy research within the field, provided us with a clear understanding of the current research status and future trends, providing a valuable reference for researchers venturing into this domain.

Previous research demonstrated the distribution of distinct microbial communities in the equine hindgut surrounding the pelvic flexure. The current study evaluated gene expression in epithelial tissues surrounding the pelvic flexure to characterize patterns that might correlate with microbial distribution. Gene expression was determined by analyzing RNA sequence data from the pelvic flexure, the left and right ventral colon, and the left and right dorsal colon. An average of 18,330 genes were expressed across the five tissues sampled. Most of the genes showed some level of expression in all five tissues. Tissue-restricted patterns of expression were also observed. Genes with restricted expression in the left ventral and left dorsal colons have communication, signaling, and regulatory functions that correlate with their known physiology. In contrast, genes expressed exclusively in the pelvic flexure have diverse functions. The ontology of genes differentially expressed between the pelvic flexure and the surrounding tissues was associated with immune functions and signaling processes. Despite being non-significant, these enrichment trends were reinforced by the functions of statistically significant expression differences between tissues of the hindgut. These results provide insight into the physiology of the equine hindgut epithelium that might influence the microbiota and its distribution.

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population.

This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.

Rheumatoid arthritis (RA) is considered a multifactorial condition where interaction between the genetic and environmental factors lead to immune dysregulation causing autoreactivity. While among the various genetic factors, HLA-DR4 and DQ8, have been reported to be the strongest risk factors, the role of various environmental factors has been unclear. Though events initiating autoreactivity remain unknown, a mucosal origin of RA has gained attention based on the recent observations with the gut dysbiosis in patients. However, causality of gut dysbiosis has been difficult to prove in humans. Mouse models, especially mice expressing RA-susceptible and -resistant HLA class II genes have helped unravel the complex interactions between genetic factors and gut microbiome. This review describes the interactions between HLA genes and gut dysbiosis in sex-biased preclinical autoreactivity and discusses the potential use of endogenous commensals as indicators of treatment efficacy as well as therapeutic tool to suppress pro-inflammatory response in rheumatoid arthritis.

The intestinal microbiota plays significant role in the physiology and functioning of host organisms. However, there is limited knowledge of the composition and evolution of microbiota-host relationships from wild ancestors to modern domesticated species. In this study, the 16S rRNA gene V3-V4 in the intestinal contents of different pig breeds was analyzed and was compared using high-throughput sequencing. This identified 18 323 amplicon sequence variants, of which the Firmicutes and Actinobacteria phyla and Bifidobacterium and Allobaculum genera were most prevalent in wild pigs (WP). In contrast, Proteobacteria and Firmicutes predominated in Chinese Shanxi Black pigs (CSB), while Firmicutes were the most prevalent phylum in Large White pigs (LW) and Iberian pigs (IB), followed by Bacteroidetes in IB and Proteobacteria in LW. At the genus level, Shigella and Lactobacillus were most prevalent in CSB and LW, while Actinobacillus and Sarcina predominated in IB. Differential gene expression together with phylogenetic and functional analyses indicated significant differences in the relative abundance of microbial taxa between different pig breeds. Although many microbial taxa were common to both wild and domestic pigs, significant diversification was observed in bacterial genes that potentially influence host phenotypic traits. Overall, these findings suggested that both the composition and functions of the microbiota were closely associated with domestication and the evolutionary changes in the host. The members of the microbial communities were vertically transmitted in pigs, with evidence of co-evolution of both the hosts and their intestinal microbial communities. These results enhance our understanding and appreciation of the complex interactions between intestinal microbes and hosts and highlight the importance of applying this knowledge in agricultural and microbiological research.

Osteoporosis, characterized by reduced bone density and heightened fracture risk, is influenced by genetic and environmental factors. This study investigates the interplay between gut microbiota, plasma metabolomics, and osteoporosis, identifying potential causal relationships mediated by plasma metabolites.

Utilizing aggregated genome-wide association studies (GWAS) data, a comprehensive two-sample Mendelian Randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1,400 plasma metabolites, and osteoporosis indicators. Causal relationships between gut microbiota, plasma metabolites, and osteoporosis were explored.

The MR analyses revealed ten gut microbiota taxa associated with osteoporosis, with five taxa positively linked to increased risk and five negatively associated. Additionally, 96 plasma metabolites exhibited potential causal relationships with osteoporosis, with 49 showing positive associations and 47 displaying negative associations. Mediation analyses identified six causal pathways connecting gut microbiota to osteoporosis through ten mediating relationships involving seven distinct plasma metabolites, two of which demonstrated suppression effects.

This study provides suggestive evidence of genetic correlations and causal links between gut microbiota, plasma metabolites, and osteoporosis. The findings underscore the complex, multifactorial nature of osteoporosis and suggest the potential of gut microbiota and plasma metabolite profiles as biomarkers or therapeutic targets in the management of osteoporosis.

Peanut Oral Immunotherapy (POIT) holds promise for remission of peanut allergy, though treatment is protracted and successful in only a subset of patients. Because the gut microbiome is linked to food allergy, we sought to identify fecal microbial predictors of POIT efficacy and to develop mechanistic insights into treatment response. Longitudinal functional analysis of the fecal microbiome of children (n=79) undergoing POIT in a first double-blind, placebo-controlled clinical trial, identified five microbial-derived bile acids enriched in fecal samples prior to POIT initiation that predicted treatment efficacy (AUC 0.71). Failure to induce disease remission was associated with a distinct fecal microbiome with enhanced capacity for bile acid deconjugation, amino acid metabolism, and increased peanut peptide degradation in vitro . Thus, microbiome mechanisms of POIT failure appear to include depletion of immunomodulatory secondary bile and amino acids and the antigenic peanut peptides necessary to promote peanut allergy desensitization and remission.

The gut microbiome plays a significant role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC), influencing oncogenesis, immune responses, and treatment outcomes. Studies have identified microbial species like Porphyromonas gingivalis and Fusobacterium nucleatum, that promote PDAC progression through various mechanisms. Additionally, the gut microbiome affects immune cell activation and response to immunotherapy, including immune checkpoint inhibitors and CAR-T therapy. Specific microbes and their metabolites play a significant role in the effectiveness of immune checkpoint inhibitors (ICIs). Alterations in the gut microbiome can either enhance or diminish responses to PD-1/PD-L1 and CTLA-4 blockade therapy. Additionally, bacterial metabolites like trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS) impact antitumor immunity, offering potential targets to augment immunotherapy responses. Modulating the microbiome through fecal microbiota transplantation, probiotics, prebiotics, dietary changes, and antibiotics shows promise in PDAC treatment, although outcomes are highly variable. Dietary modifications, particularly high-fiber diets and specific fat consumption, influence microbiome composition and impact cancer risk. Combining microbiome-based therapies with existing treatments holds potential for improving PDAC therapy outcomes, but further research is needed to optimize their effectiveness.

Our study focuses on the microbial and metabolomic profile changes during the adenoma stage, as adenomas can be considered potential precursors to colorectal cancer through the adenoma-carcinoma sequence. Identifying possible intervention targets at this stage may aid in preventing the progression of colorectal adenoma (CRA) to malignant lesions. Furthermore, we evaluate the efficacy of combined microbial and metabolite biomarkers in detecting CRA.

Fecal metagenomic and serum metabolomic analyses were performed for the discovery of alterations of gut microbiome and metabolites in CRA patients (n = 26), Colorectal cancer (CRC) patients (n = 19), Familial Adenomatous Polyposis (FAP) patients (n = 10), and healthy controls (n = 20). Finally, analyzing the associations between gut microbes and metabolites was performed by a Receiver Operating Characteristic (ROC) curve.

Our analysis present that CRA patients differ significantly in gut microflora and serum metabolites compared with healthy controls, especially for Lachnospiraceae and Parasutterella. Its main metabolite, butyric acid, concentrations were raised in CRA patients compared with the healthy controls, indicating its role as a promoter of colorectal tumorigenesis. α-Linolenic acid and lysophosphatidylcholine represented the other healthy metabolite for CRA. Combining five microbial and five metabolite biomarkers, we differentiated CRA from CRC with an Area Under the Curve (AUC) of 0.85 out of this performance vastly superior to the specificity recorded by traditional markers CEA and CA199 in such differentiation of these conditions.

The study underlines significant microbial and metabolic alterations in CRA with a novel insight into screening and early intervention of its tumorigenesis.

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Regular physical activity promotes health benefits and contributes to develop the individual biological potential. Chronical physical activity performed at moderate and high-intensity is the intensity more favorable to produce health development in athletes and improve the gut microbiota balance. The athletic microbiome is characterized by increased microbial diversity and abundance as well as greater phenotypic versatility. In addition, physical activity and microbiota composition have bidirectional effects, with regular physical activity improving microbial composition and microbial composition enhancing physical performance. The improvement of physical performance by a healthy microbiota is related to different phenotypes: i) efficient metabolic development, ii) improved regulation of intestinal permeability, iii) favourable modulation of local and systemic inflammatory and efficient immune responses, iv) efective regulation of systemic pH and, v) protection against acute stressful events such as environmental exposure to altitude or heat. The type of sport, both intensity or volume characteristics promote microbiota specialisation. Individual assessment of the state of the gut microbiota can be an effective biomarker for monitoring health in the medium to long term. The relationship between the microbiota and the rest of the body is bidirectional and symbiotic, with a full connection between the systemic functions of the nervous, musculoskeletal, endocrine, metabolic, acid-base and immune systems. In addition, circadian rhythms, including regular physical activity, directly influence the adaptive response of the microbiota. In conclusion, regular stimuli of moderate- and high-intensity physical activity promote greater diversity, abundance, resilience and versatility of the gut microbiota. This effect is highly beneficial for human health when healthy lifestyle habits including nutrition, hydration, rest, chronoregulation and physical activity.

Germ-free (GF) mice, which are depleted of their resident microbiota, are the gold standard for exploring the role of the microbiome in health and disease; however, they are of limited value in the study of human-specific pathogens because they do not support their replication. Here, we develop GF mice systemically reconstituted with human immune cells and use them to evaluate the role of the resident microbiome in the acquisition, replication and pathogenesis of two human-specific pathogens, Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV). Comparison with conventional (CV) humanized mice showed that resident microbiota enhance the establishment of EBV infection and EBV-induced tumorigenesis and increase mucosal HIV acquisition and replication. HIV RNA levels were higher in plasma and tissues of CV humanized mice compared with GF humanized mice. The frequency of CCR5+ CD4+ T cells throughout the intestine was also higher in CV humanized mice, indicating that resident microbiota govern levels of HIV target cells. Thus, resident microbiota promote the acquisition and pathogenesis of two clinically relevant human-specific pathogens.