Host Gut Microbiota Research Articles

Host-specific effects of Eubacterium species on Rg3-mediated modulation of osteosarcopenia in a genetically diverse mouse population

BackgroundOsteosarcopenia, characterized by the simultaneous loss of bone and muscle mass, is a serious health problem in the aging population. This study investigated the interplay between host genetics, gut microbiota, and musculoskeletal health in a mouse model of osteosarcopenia, exploring the therapeutic potential of gut microbiota modulation.MethodsWe examined the effects of Rg3, a phytochemical, on osteosarcopenia and its interactions with host genetics and gut microbiota in six founder strains of the Collaborative Cross (CC) population. Subsequently, we evaluated the therapeutic potential of Eubacterium nodatum (EN) and Eubacterium ventriosum (EV), two gut microbes identified as significant correlates of Rg3-mediated osteosarcopenia improvement, in selected C57BL/6 J (B6) and 129S1/SvImJ (129S1) mouse strains.ResultsRg3 treatment altered gut microbiota composition aligned with osteosarcopenia phenotypes, which response varied depending on host genetics. This finding enabled the identification of two microbes in the Eubacterium genus, potential mediator of Rg3 effect on osteosarcopenia. Oral administration of EN and EV differentially impacted bone density, muscle mass, exercise performance, and related gene expression in a mouse strain-specific manner. In 129S1 mice, EN and EV significantly improved these parameters, effectively reversing osteosarcopenic phenotypes. Mechanistic investigations revealed that these effects were mediated through the modulation of osteoblast differentiation and protein degradation pathways. In contrast, EN and EV did not significantly improve osteosarcopenic phenotypes in B6 mice, although they did modulate mitochondrial biogenesis and microbial diversity.ConclusionsOur findings underscore the complex interplay between host genetics and the gut microbiota in osteosarcopenia and emphasize the need for personalized treatment strategies. EN and EV exhibit strain-specific therapeutic effects, suggesting that tailoring microbial interventions to individual genetic backgrounds may be crucial for optimizing treatment outcomes.9Nfyi13u2tifXMNNi2cAAqVideo Graphical

Molecular patterns of microbial and metabolic interactions in septic patients with persistent lymphopenia

BackgroundPersistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear. MethodsThis single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n=21) and non-persistent lymphopenia (<3d) (n=15). ResultsThe persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3+T/LY, CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, Th1 cells, Th2 cells, CD45RA+Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia. ConclusionIn the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.

The microbiome's influence on obesity: mechanisms and therapeutic potential.

In 2023, the World Obesity Atlas Federation concluded that more than 50% of the world's population would be overweight or obese within the next 12 years. At the heart of this epidemic lies the gut microbiota, a complex ecosystem that profoundly influences obesity-related metabolic health. Its multifaced role encompasses energy harvesting, inflammation, satiety signaling, gut barrier function, gut-brain communication, and adipose tissue homeostasis. Recognizing the complexities of the cross-talk between host physiology and gut microbiota is crucial for developing cutting-edge, microbiome-targeted therapies to address the global obesity crisis and its alarming health and economic repercussions. This narrative review analyzed the current state of knowledge, illuminating emerging research areas and their implications for leveraging gut microbial manipulations as therapeutic strategies to prevent and treat obesity and related disorders in humans. By elucidating the complex relationship between gut microflora and obesity, we aim to contribute to the growing body of knowledge underpinning this critical field, potentially paving the way for novel interventions to combat the worldwide obesity epidemic.

Invasive Fascioloides magna infections impact gut microbiota in a definitive host in Europe

Invasive parasites that expand their natural range can be a threat to wildlife biodiversity and may pose a health risk to non-adapted, naive host species. The invasive giant liver fluke, Fascioloides magna, native to North America, has extended its range in Europe and uses mainly red deer (Cervus elaphus) as definitive hosts. The penetration of the intestinal barrier by the young flukes to reach the liver via the abdominal cavity as well as the release of fluke metabolism products and excreta with the bile and/or changes in the microbial community of the biliary system may enable the translocation of intestinal bacteria across the intestinal barrier and, in turn, could be associated with inflammation and changes in the intestinal bacterial community. The gut commensal community plays a key role in host nutrition and interacts with cells of the immune system to maintain host health. For this study, the gut bacterial community of red deer infected with F. magna and of non-infected red deer from one of the largest forest ecosystems in Central Europe, located on the border between the Czech Republic and Germany, was investigated. The individual fluke burden was associated with changes in the gut microbial composition of the gut of infected individuals, whereas the diversity and composition of the gut bacteria were only slightly different between fluke-infected and uninfected deer. Several bacterial taxa at the genus level were unique to individuals carrying either one or many liver flukes. Our results suggest that the microbiota of red deer is stable to perturbation by low numbers of F. magna. However, a larger parasite burden may cause changes in the gut microbial composition in definitive hosts implying that non-invasive fecal microbiome assessments could serve as indicator for wildlife health monitoring.

Integrative analysis of gut microbiome and host transcriptome reveal novel molecular signatures in Hashimoto's thyroiditis

BackgroundHashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets.MethodsWe recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT.ResultsIntegrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis.ConclusionOur study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Weizmannia coagulans BC99 affects valeric acid production via regulating gut microbiota to ameliorate inflammation and oxidative stress responses in Helicobacter pylori mice.

Helicobacter pylori is a highly prevalent pathogen in human gastric mucosa epithelial cells with strong colonization ability. Weizmannia coagulans is a kind of active microorganism that is beneficial to the improvement of host gut microbiota balance and can prevent and treat intestinal diseases. We investigated the beneficial effects of W. coagulans BC99 in H. pylori infected mice and measured inflammation response, oxidative stress, and gut microbiota. Results showed that BC99 could alleviate the gastric inflammation, inhibit the increasing of inflammation parameters endotoxin, interleukin-10, transforming growth factor-β, and interferon-γ and oxidative stress myeloperoxidase and malondialdehyde, promote the levels of superoxide dismutase and catalase. Furthermore, 16S rRNA gene sequencing analysis revealed that BC99 reversed the change of gut microbiota by reducing the abundance of Olsenella, Candidatus_Saccharimonas, Monoglobus, and increasing the abundance of Tyzzerella. Meanwhile, BC99 caused elevated levels of Ligilactobacillus and Lactobacillus. In view of the beneficial effect of BC99 on the content of short-chain fatty acid, valeric acid with sodium valerate interfered with H. pylori infection in mice found that valeric acid had a good restorative effect of H. pylori infection relating inflammation and oxidative stress responses. These results suggest that W. coagulans BC99 can be used as a potential probiotic to prevent and treat H. pylori infection by regulating the inflammation, oxidative stress, and gut microbiota.

Pristimerin Alleviates DSS-Induced Colitis in Mice by Modulating Intestinal Barrier Function, Gut Microbiota Balance and Host Metabolism.

Pristimerin is a pentacyclic triterpenoid mainly derived from Celastraceae plants such as Maytenus ilicifolia, which has been traditionally used for the treatment of gastrointestinal disorders. Pharmacological studies have shown that pristimerin exhibited anti-inflammatory, antioxidant, anticancer and antibacterial activities. However, the potential mechanism of pristimerin for the treatment of ulcerative colitis (UC) remains elusive. In the present study, pristimerin could effectively inhibit the NO generation induced by LPS in RAW 264.7 cells and upregulate the decreased expression of tight junction proteins such as occludin and claudin-1. In vivo, oral administration of pristimerin (0.5 mg/kg and 1 mg/kg) could significantly relieve UC symptoms such as body weight loss, disease activity index, shortened colon length and colonic pathological damage. Meanwhile, pristimerin decreased the TNF-α, MPO and MDA levels and increased the levels of IL-10, IL-22, SOD activity, occludin and claudin-1 in colon tissues. Gut microbiota analysis of cecum contents revealed that pristimerin treatment effectively alleviated gut microbiota dysbiosis. Additionally, serum metabolomics showed that 33 potential biomarkers involving lipid and tryptophan metabolism were identified, which may account for the therapeutic effects of pristimerin on UC mice. In conclusion, our findings indicate that pristimerin attenuates UC symptoms in DSS-induced mice through modulating intestinal barrier integrity, gut microbiota composition, lipid and tryptophan metabolism.

Pathobiont and symbiont contribute to microbiota homeostasis through Malpighian tubules-gut countercurrent flow in Bactrocera dorsalis.

Host-gut microbiota interactions are more complex than good or bad. Both gut symbiotic bacteria and pathobionts can provide essential functions to their host in one scenario and yet be detrimental to host health in another. So, these gut-dwelling bacteria must be tightly controlled to avoid harmful effects on the host. However, how pathobionts and other symbiotic bacteria coordinate to establish a host immune defense system remains unclear. Here, using a Tephritidae fruit fly Bactrocera dorsalis, we report that both pathobionts and other gut symbiotic bacteria release tyramine, which is recognized by the host insects. These tyramines induce the formation of insect-conserved Malpighian tubules-gut countercurrent flow upon bacterial infection, which requires tyramine receptors and aquaporins. At the same time, pathobionts but not gut symbiotic bacteria induce the generation of reactive oxygen species, which are preserved by the countercurrent flow, promoting bacteria elimination through increasing gut peristalsis. More importantly, our results show that the Malpighian tubules-gut countercurrent flow maintains proper microbiota composition. Our work suggests a model where pathobiont-induced reactive oxygen species are preserved by Malpighian tubules-gut countercurrent flow involving both pathobionts and symbiotic bacteria. Furthermore, our work provides a Malpighian tubules-gut interaction that ensures efficient maintenance of the gut microbiota.

Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

Unraveling the Gut Microbiota: Implications for Precision Nutrition and Personalized Medicine.

Recent studies have shown a growing interest in the complex relationship between the human gut microbiota, metabolism, and overall health. This review aims to explore the gut microbiota-host association, focusing on its implications for precision nutrition and personalized medicine. The objective is to highlight how gut microbiota modulate metabolic and immune functions, contributing to disease susceptibility and wellbeing. The review synthesizes recent research findings, analyzing key studies on the influence of gut microbiota on lipid and carbohydrate metabolism, intestinal health, neurobehavioral regulation, and endocrine signaling. Data were drawn from both experimental and clinical trials examining microbiota-host interactions relevant to precision nutrition. Our findings highlight the essential role of gut microbiota-derived metabolites in regulating host metabolism, including lipid and glucose pathways. These metabolites have been found to influence immune responses and gut barrier integrity. Additionally, the microbiota impacts broader physiological processes, including neuroendocrine regulation, which could be crucial for dietary interventions. Therefore, understanding the molecular mechanisms of dietary-microbiota-host interactions is pivotal for advancing personalized nutrition strategies. Tailored dietary recommendations based on individual gut microbiota compositions hold promise for improving health outcomes, potentially revolutionizing future healthcare approaches across diverse populations.

Uncovering new Firmicutes species in vertebrate hosts through metagenome-assembled genomes with potential for sporulation.

Metagenome-assembled genomes (MAGs) have contributed to identifying non-culturable microorganisms and understanding their ecological functions. MAGs offer an advantage in investigating sporulation-associated genes, especially given the difficulty of isolating many species residing in the gut microbiota of multiple hosts. Bacterial sporulation is a key survival mechanism with implications for pathogenicity and biotechnology. Here, we investigate MAGs from vertebrate hosts, emphasizing taxonomic identification and identifying sporulation-associated genes in potential novel species within the Firmicutes phylum. We identified potential new species in the classes Clostridia (Borkfalkiaceae, Lachnospiraceae, Monoglobaceae, and Oscillospiraceae families) and Bacilli (Bacillaceae and Erysipelotrichaceae families) through phylogenetic and functional pathway analyses, highlighting their sporulation potential. Our study covers 146 MAGs, 124 of them without refined taxonomic assignments at the family level. We found that Clostridia and Bacilli have unique sporulation gene profiles in the refined family MAGs for cattle, swine, poultry, and human hosts. The presence of genes related to Spo0A regulon, engulfment, and spore cortex in MAGs underscores fundamental mechanisms in sporulation processes in currently uncharacterized species with sporulation potential from metagenomic dark matter. Furthermore, genomic analyses predict sporulation potential based on gene presence, genome size, and metabolic pathways involved in spore formation. We emphasize MAGs covering families not yet characterized through the phylogenetic analysis, and with extensive potential for spore-forming bacteria within Clostridia, Bacilli, UBA4882, and UBA994 classes. These findings contribute to exploring spore-forming bacteria, which provides evidence for novel species diversity in multiple hosts, their adaptive strategies, and potential applications in biotechnology and host health.IMPORTANCESpores are essential for bacterial survival in harsh environments, facilitating their persistence and adaptation. Exploring sporulation-associated genes in metagenome-assembled genomes (MAGs) from different hosts contributes to clinical and biotechnological domains. Our study investigated the extent of genes associated with bacterial sporulation in MAGs from poultry, swine, cattle, and humans, revealing these genes in uncultivated bacteria. We identified potential novel Firmicutes species with sporulation capabilities through phylogenetic and functional analyses. Notably, MAGs belonging to Clostridia, Bacilli, and unknown classes, namely UBA4882 and UBA994, remained uncharacterized at the family level, which raises the hypothesis that sporulation would also be present in these genomes. These findings contribute to our understanding of microbial adaptation and have implications for microbial ecology, underlining the importance of sporulation in Firmicutes across different hosts. Further studies into novel species and their sporulation capability can contribute to bacterial maintenance mechanisms in various organisms and their applications in biotechnology studies.

Comprehensive genomic analysis and evaluation of in vivo and in vitro safety of Heyndrickxia coagulans BC99

This study aimed to evaluate the safety profile and beneficial effects of Heyndrickxia coagulans strain BC99 (BC99) for potential use in functional foods and pharmaceuticals. We began with whole genome sequencing of BC99, followed by a comprehensive safety assessment comprising genome analysis, hemolysis, cytotoxicity, antibiotic susceptibility tests, and cell adhesion and tolerance studies, along with acute and subacute oral toxicity studies in animal models. BC99 was isolated from a well-characterized collection originating from the feces of a healthy infant. Our results indicated no hemolytic activity on Columbia blood agar plates and broad antibiotic sensitivity, including to gentamicin, ampicillin, chloramphenicol, ciprofloxacin, and others. Cytotoxicity testing confirmed no adverse effects on HT-29 cells and significant adhesive properties to intestinal epithelial cells. Tolerance tests demonstrated over 90% viability of BC99 under simulated gastrointestinal conditions. In vivo studies in mice and rats confirmed the absence of adverse effects following oral administration. Collectively, these findings support BC99’s robust tolerance to gastrointestinal environments, strong adhesion capabilities, and a broad spectrum of antibiotic resistance, underlining its potential as a safe and effective agent for gut microbiota modulation and host health enhancement.

Microbial alchemists unlock honeybee cognition

In this issue of Cell Host & Microbe, Zhong etal.1 uncover gut microbiota-host connections that promote cognitive function in honeybees. They discover the role of the microbiota in lipid metabolism and the synthesis of lipid-derived neurotransmitters, which modulate the endocannabinoid system.

Metabolic interactions of host-gut microbiota: New possibilities for the precise diagnosis and therapeutic discovery of gastrointestinal cancer in the future-a review.

Gastrointestinal (GI) cancer continues to pose a significant global health challenge. Recent advances in our understanding of the complex relationship between the host and gut microbiota have shed light on the critical role of metabolic interactions in the pathogenesis and progression of GI cancer. In this study, we examined how microbiota interact with the host to influence signalling pathways that impact the formation of GI tumours. Additionally, we investigated the potential therapeutic approach of manipulating GI microbiota for use in clinical settings. Revealing the complex molecular exchanges between the host and gut microbiota facilitates a deeper understanding of the underlying mechanisms that drive cancer development. Metabolic interactions hold promise for the identification of microbial signatures or metabolic pathways associated with specific stages of cancer. Hence, this study provides potential strategies for the diagnosis, treatment and management of GI cancers to improve patient outcomes.

16S rRNA Gene Sequencing Combined with Metabolomics to Explore Intestinal Flora and Metabolic Changes in Young Febrile Rats and the Mechanism of Xiangqin Jiere Granules.

Xiangqin Jiere Granules (XQJRG), a Chinese patent medicine used to treat acute fever in children caused by colds, seasonal flu, and coronavirus disease 2019has been proven to have antipyretic and anti-inflammatory effects in young febrile rats. Fever is known to affect the host-gut microbiota crosstalk. However, the pharmacological mechanism of XQJRG in this regard remains unclear. This study utilized a young febrile rat model previously reported by our team and extended the rat body temperature monitoring period following drug administration to explore the differences in efficacy between XQJRG and the commonly used pediatric antipyretic ibuprofen. Subsequently, the colonic contents of rats were analyzed using 16S rRNA gene sequencing and untargeted metabolomics. The short-chain fatty acid content was quantified using high-throughput targeted metabolomics. The expression of short-chain fatty acid receptors and pro-inflammatory genes in the colonic tissue was evaluated using quantitative real-time PCR, Western blot, and enzyme-linked immunosorbent assay. XQJRG showed a longer antipyretic duration than ibuprofen. XQJRG improved dysbiosis of the intestinal microbiota in young febrile rats, bringing its flora composition closer to that of normal rats. It significantly increased the relative abundance of s_Phascolarctobacterium_faecium and s_Roseburia_sp. related to the production of short-chain fatty acids (SCFAs), the contents of butyric acid and nonanoic acid and protein levels of SCFAs receptor GPR41. Moreover, XQJRG significantly increased the levels of metabolites with anti-inflammatory effects, reduced the contents of metabolites directly associated with fever, and decreased the levels of pro-inflammatory cytokines interleukin-1β and monocyte chemotactic protein-1 in the colon of young febrile rats to normal levels. XQJRG exhibited a more stable and persistent antipyretic effect in young febrile rats compared to ibuprofen. Its mechanism was at least partially attributed to regulating intestinal flora disorders, increasing anti-inflammatory metabolites, and inhibiting the production of inflammatory factors in young febrile rats.

Oral co-administration of Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 improves host defense against influenza A virus infection.

Influenza is an important zoonotic disease that persistently threatens global public health. While it is widely acknowledged that probiotics can modulate the host response to protect the host against infectious disease, the prophylactic efficacy on respiratory viral infection and the detailed mechanism remains elusive. Lactobacillus, the most commonly used probiotic widely applied in food production, has garnered significant attention. In our study utilizing both C57BL/6 and BALB/c mouse models, we explored the protective effect against two strains of influenza virus, A/Mink/China/01/2014(H9N2) and A/California/04/2009(H1N1), through the administration of Lactiplantibacillus plantarum strain 16 (L. plantarum 16) and Lacticaseibacillus rhamnosus strain P118 (L. rhamnosus P118), aiming to identify robust probiotic strains with antiviral properties. Our findings indicate that administering L. plantarum 16 or L. rhamnosus P118 alone does not provide sufficient protection against influenza. However, the co-administration of L. plantarum 16 and L. rhamnosus P118 dramatically reduces viral titers in the respiratory tract and lung, thereby markedly alleviating the clinical symptoms, improving prognosis, and reducing mortality. The mechanisms underlying this effect involve the modulation of host gut microbiota and metabolism through the co-administration of L. plantarum 16 and L. rhamnosus P118, resulting in enrichment of Firmicutes and enhancement of phenylalanine-related metabolism, ultimately leading to an augmentation of the antiviral immune response. Notably, we identified that the circulating metabolic molecule 2-Hydroxycinnamic acid plays a significant role in combating influenza. Our data suggest the potential utility of L. plantarum 16 and L. rhamnosus P118 two-bacterium or 2-Hydroxycinnamic acid in preventing influenza.IMPORTANCEVaccination represents the most optimal strategy to control influenza. Nevertheless, influenza viruses constantly evolve due to antigenic drift and shift, leading to the need for regular updates on influenza vaccines. Additionally, vaccination failure poses significant challenges to influenza prevention. Therefore, it is essential and beneficial to identify novel or universal antiviral measures to protect against influenza. While cumulative data suggest that probiotics offer protection against infectious diseases, the specific mechanisms, such as the effective metabolites or components, remain largely unknown. Our research discovered the capacity of combinational two-bacterium Lactiplantibacillus plantarum 16 and Lacticaseibacillus rhamnosus P118 to fight against influenza infection in a mouse model. The protection may occur through modulating the host's gut microbiota and metabolism, further influencing the host's antiviral immune response. Notably, we have identified a novel metabolic molecule, 2-Hydroxycinnamic acid, capable of enhancing antiviral response and restricting viral replication in vivo.

Trace antibiotic exposure affects murine gut microbiota and metabolism

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied. We provide evidence of trace antibiotic exposure affecting the host's gut microbiota using a mouse model exposed to trace amounts of azithromycin (AZI) or ciprofloxacin (CIP) in drinking water. AZI exposure in males changed the distribution of gram-positive (Firmicutes and Bacteroidetes) and gram-negative (Proteobacteria, Fusobacteria, and Verrucomicrobia) bacteria at an early age. Both AZI and CIP resulted in abnormal microbiota maturation. Additionally, the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, in females is affected. Serum hormone and metabolome levels shifted after trace antibiotic exposure. AZI and CIP exposure broadly disrupted original host-microbe interaction relationships between the gut microbiota and SCFAs or serum metabolites. In this study, we demonstrated that trace antibiotic exposure was associated with extensive gut microbiota and metabolism perturbation in mice and that the potential health risks in susceptible populations should be considered.

Bioactive Compounds and Their Chondroprotective Effects for Osteoarthritis Amelioration: A Focus on Nanotherapeutic Strategies, Epigenetic Modifications, and Gut Microbiota.

In degenerative joint disease like osteoarthritis (OA), bioactive compounds like resveratrol, epigallocatechin gallate, curcumin, and other polyphenols often target various signalling pathways, including NFκB, TGFβ, and Wnt/β-catenin by executing epigenetic-modifying activities. Epigenetic modulation can target genes of disease pathophysiology via histone modification, promoter DNA methylation, and non-coding RNA expression, some of which are directly involved in OA but have been less explored. OA patients often seek options that can improve the quality of their life in addition to existing treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Although bioactive and natural compounds exhibit therapeutic potential against OA, several disadvantages loom, like insolubility and poor bioavailability. Nanoformulated bioactive compounds promise a better way to alleviate OA since they also control systemic events, including metabolic, immunological, and inflammatory responses, by modulating host gut microbiota that can regulate OA pathogenesis. Recent data suggest gut dysbiosis in OA. However, limited evidence is available on the role of bioactive compounds as epigenetic and gut modulators in ameliorating OA. Moreover, it is not known whether the effects of polyphenolic bioactive compounds on gut microbial response are mediated by epigenetic modulatory activities in OA. This narrative review highlights the nanotherapeutic strategies utilizing bioactive compounds, reporting their effects on chondrocyte growth, metabolism, and epigenetic modifications in osteoarthritis amelioration.

Parameter Estimation of Host Genomic and Gut Microbiota Contribution to Growth and Feed Efficiency Traits in Meat Rabbits.

Rabbits can efficiently utilize plant fibers that are indigestible to humans, and hence may contribute to the alleviation of feed-food competition. Therefore, it is economically and ecologically important to genetically improve the growth performance and feed efficiency of meat rabbits. In this study, we combined pedigree, genomic, and gut microbiota data to estimate genetic and microbial parameters for nine growth and feed efficiency traits of 739 New Zealand White rabbits, including body weight (BW) at 35 (BW35), 70 (BW70), and 84 (BW84) days of age, and average daily gain (ADG), feed conversion ratio (FCR), and residual feed intake (RFI) within two age intervals of 35-70 days (ADG70, FCR70, and RFI70) and 35-84 days (ADG84, FCR84, and RFI84). Based on single-step genomic best linear unbiased prediction, three BW traits and two ADG traits had the high estimates (±standard error, SE) of heritability, ranging from 0.44 ± 0.13 of BW35 to 0.66 ± 0.08 of BW70. Moderate heritabilities were observed for RFI70 (0.22 ± 0.07) and RFI84 (0.29 ± 0.07), whereas the estimates did not significantly deviate from zero for the two FCR traits. There was moderate positive genetic correlation (±SE) between BW70 and ADG70 (0.579 ± 0.086), but BW70 did not correlate with RFI70. Based on microbial best linear unbiased prediction, the estimates of microbiability did not significantly deviate from zero for any trait. Based on the combined use of genomic and gut microbiota data, the parameters obtained in this study could help us to implement efficient breeding schemes in meat rabbits.

The modulation of intestinal commensal bacteria possibly contributes to the growth and immunity promotion in Epinephelus akaara after feeding the antimicrobial peptide Scy-hepc.

Our previous study revealed that feeding the antimicrobial peptide (AMP) product Scy-hepc significantly enhances the growth of mariculture fish through the activation of the GH-Jak2-STAT5-IGF1 axis. However, the contribution of gut microbiota to this growth enhancement remains unclear. This study aimed to elucidate the potential mechanism involved in intestinal absorption and modulation of gut microbiota in Epinephelus akaara following Scy-hepc feeding. The results showed that a 35day regimen of Scy-hpec markedly promoted the growth of E. akaara compared to groups supplemented with either florfenicol, B. subtilis, or a vector. The growth enhancement is likely attributed to alterations in microbiota colonization in the foregut and midgut, characterized by an increasing abundance of potential probiotics (Rhizobiaceae and Lysobacter) and a decreased abundance of opportunistic pathogens (Psychrobacter and Brevundimonas) as determined by 16S rRNA analysis. Additionally, similar to the effect of florfenicol feeding, Scy-hepc significantly improved host survival rate by over 20% in response to a lethal dose challenge with Edwardsiella tarda. Further investigations demonstrated that Scy-hepc is absorbed by the fish foregut (20-40min) and midgut (20-30min) as confirmed by Western blot, ELISA, and Immunofluorescence. The absorption of Scy-hepc affected the swimming, swarming and surfing motility of Vibrio harveyi and Bacillus thuringiensis isolated from E. akaara's gut. Moreover, Scy-hepc induced the downregulation of 40 assembly genes and the upregulation expression of 5, with the most significant divergence in gene expression between opportunistic pathogens and probiotics concentrated in their motility genes (PomA/B, MotA/B). In summary, this study shows that feeding AMP Scy-hepc can promote growth and bolster immunity in E. akaara. These beneficial effects are likely due to the absorption of Scy-hepc in the fish's foregut and midgut, which modulates the colonization and motility of commensal bacteria, leading to favorable changes in the composition of the foregut and midgut microbiota. Therefore, a profound understanding of the mechanisms by which antimicrobial peptides affect host gut microbiota will contribute to a comprehensive assessment of their advantages and potential application prospects as substitutes for antibiotics in fish health and improving aquaculture practices.