Gut microbiota intervention alleviates pulmonary inflammation in broilers exposed to fine particulate matter from broiler house.

The gut microbiota of poultry is influenced by a variety of factors, including feed, drinking water, airborne dust, and footpads, among others. Gut microbiota can affect the immune reaction and inflammation in the lungs. To investigate the effect of gut microbiota variation on lung inflammation induced by PM2.5 (fine particulate matter) in broilers, 36 Arbor Acres (AA) broilers were randomly assigned to three groups: control group (CON), PM2.5 exposure group (PM), and PM2.5 exposure plus oral antibiotics group (PMA). We used non-absorbable antibiotics (ABX: neomycin and amikacin) to modify the microbiota composition in the PMA group. The intervention was conducted from the 18th to the 28th day of age. Broilers in the PM and PMA groups were exposed to PM by a systemic exposure method from 21 to 28 days old, and the concentration of PM2.5 was controlled at 2 mg/m3. At 28 days old, the lung injury score, relative mRNA expression of inflammatory factors, T-cell differentiation, and dendritic cell function were significantly increased in the PM group compared to the CON group, and those of the PMA group were significantly decreased compared to the PM group. There were significant differences in both α and ß diversity of cecal microbiota among these three groups. Numerous bacterial genera showed significant differences in relative abundance among the three groups. In conclusion, gut microbiota could affect PM2.5-induced lung inflammation in broilers by adjusting the capacity of antigen-presenting cells to activate T-cell differentiation. IMPORTANCE: Gut microbes can influence the development of lung inflammation, and fine particulate matter collected from broiler houses can lead to lung inflammation in broilers. In this study, we explored the effect of gut microbes modified by intestinal non-absorbable antibiotics on particulate matter-induced lung inflammation. The results showed that modification in the composition of gut microbiota could alleviate lung inflammation by attenuating the ability of dendritic cells to stimulate T-cell differentiation, which provides a new way to protect lung health in poultry farms.

L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.

SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

Effect of microplastics on oxytetracycline trophic transfer: Immune, gut microbiota and antibiotic resistance gene responses.

Microplastics and antibiotics are prevalent and emerging pollutants in aquatic ecosystems, but their interactions in aquatic food chains remain largely unexplored. This study investigated the impact of polypropylene microplastics (PP-MPs) on oxytetracycline (OTC) trophic transfer from the shrimp (Neocaridina denticulate) to crucian carp (Carassius auratus) by metagenomic sequencing. The carrier effects of PP-MPs promoted OTC bioaccumulation and trophic transfer, which exacerbated enterocyte vacuolation and hepatocyte eosinophilic necrosis. PP-MPs enhanced the inhibitory effect of OTC on intestinal lysozyme activities and complement C3 levels in shrimp and fish, and hepatic immunoglobulin M levels in fish (p < 0.05). Co-exposure of MPs and OTC markedly increased the abundance of Actinobacteria in shrimp and Firmicutes in fish, which caused disturbances in carbohydrate, amino acid, and energy metabolism. Moreover, OTC exacerbated the enrichment of antibiotic resistance genes (ARGs) in aquatic animals, and PP-MPs significantly increased the diversity and abundance of ARGs and facilitated the trophic transfer of teta and tetm. Our findings disclosed the impacts of PP-MPs on the mechanism of antibiotic toxicity in aquatic food chains and emphasized the importance of gut microbiota for ARGs trophic transfer, which contributed to a deeper understanding of potential risks posed by complex pollutants on aquatic ecosystems.

Global analysis of the adverse effects of micro- and nanoplastics on intestinal health and microbiota of fish.

The wide occurrence of micro- and nanoplastics (MPs/NPs) within aquatic ecosystems has raised increasing concerns regarding their potential effects on aquatic organisms. However, the effects of MPs/NPs on intestinal health and microbiota of fish remain controversial, and there is a lack of comprehensive understanding regarding how the impact of MPs/NPs is influenced by MPs/NPs characteristics and experimental designs. Here, we conducted a global analysis to synthesize the effects of MPs/NPs on 47 variables associated with fish intestinal health and microbiota from 118 studies. We found that MPs/NPs generally exerted obvious adverse effects on intestinal histological structure, permeability, digestive function, immune and oxidative-antioxidative systems. By contrast, MPs/NPs showed slight effects on intestinal microbial variables. Further, we observed that the responses of intestinal variables to MPs/NPs were significantly regulated by MPs/NPs characteristics and experimental designs. For instance, polyvinyl chloride plastics showed higher toxicity to fish gut than polyethylene and polystyrene did. Additionally, larval fish appeared to be more sensitive to MPs/NPs than juvenile fish. Collectively, this study highlights the potential impacts of MPs/NPs on intestinal health and microbiota of fish, and underscores the determinant role of MPs/NPs characteristics and experimental designs in MPs/NPs toxicity.

Rumen fermentation parameters and papillae development in Simmental growing bulls with divergent residual feed intake.

Residual feed intake (RFI), a widespread index used to measure animal feed efficiency, is influenced by various individual biological factors related to inter-animal variation that need to be assessed. Herein, 30 Simmental bulls, raised under the same farm conditions, were divided on the basis of RFI values into a high efficient group (HE, RFI =  - 1.18 ± 0.33 kg DM/d, n = 15) and a low efficient group (LE, RFI = 0.92 ± 0.35 kg DM/d, n = 15). Subsequently, bulls were slaughtered at an average BW of 734 ± 39.4 kg. Their ruminal fermentation traits were analysed immediately after slaughtering and after 24 h of in vitro incubation. Furthermore, ruminal micro-biota composition and ruminal papillae morphology were examined. The LE group exhibited a higher propionate concentration as a percentage of total volatile fatty acids (17.3 vs 16.1%, P = 0.04) in the rumen fluid collected during slaughtering, which was also confirmed after in vitro fermentation (16.6 vs 15.4% respectively for LE and HE, P = 0.01). This phenomenon resulted in a significant alteration in the acetate-to-propionate ratio (A:P) with higher values for the HE group, both after slaughter (4.01 vs 3.66, P = 0.02) and after in vitro incubation (3.78 vs 3.66, P = 0.02). Methane production was similar in both groups either as absolute production (227 vs 218 mL for HE and LE, respectively) or expressed as a percentage of total gas (approximately 22%). Even if significant differences (P < 0.20) in the relative abundance of some bacterial genera were observed for the two RFI groups, no significant variations were observed in the alpha (Shannon index) and beta (Bray-Curtis index) diversity. Considering the papillae morphology, the LE subjects have shown higher length values (6.26 vs 4.90 mm, P < 0.01) while HE subjects have demonstrated higher papillae density (46.4 vs 40.5 n/cm2, P = 0.02). Histo-morphometric analysis did not reveal appreciable modifications in the total papilla thickness, boundaries or surface between the experimental groups. In conclusion, our results contribute to efforts to analyse the factors affecting feed efficiency at the ruminal level. Propionate production, papillae morphology and a few bacterial genera certainly play a role in this regard, although not a decisive one.

Effects of intestinal Desulfovibrio bacteria on host health and its potential regulatory strategies: A review.

Increasing studies have focused on the relationship between Desulfovibrio bacteria (DSV) and host health in recent years. However, little is known about the mechanisms by which DSV affects host health and the strategies to accurately regulate DSV numbers. This review mainly presents the relationship between DSV and host health, potential modulatory strategies, and the potential mechanisms affecting host health. Evidence suggests that DSV can both promote host health and induce the occurrence and development of disease, and these effects are closely related to its metabolites (e.g., H2S and short-chain fatty acids) and biofilm. DSV abundance in the intestine is influenced by probiotics, prebiotics, diet, lifestyle, and drugs.

Bile acid metabolism is altered in learning and memory impairment induced by chronic lead exposure.

Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.

Bazedoxifene attenuates dextran sodium sulfate-induced colitis in mice through gut microbiota modulation and inhibition of STAT3 and NF-κB pathways.

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract for which treatment options remain limited. In this study, we used a dual-luciferase-based screening of an FDA-approved drug library, identifying Bazedoxifene (BZA) as an inhibitor of the NF-κB pathway. We further investigated its therapeutic effects in a dextran sodium sulfate (DSS)-induced colitis model and explored its impact on gut microbiota regulation and the underlying molecular mechanisms. Our results showed that BZA significantly reduced DSS-induced colitis symptoms in mice, evidenced by decreased colon length shortening, lower histological scores, and increased expression of intestinal mucosal barrier-associated proteins, such as Claudin 1, Occludin, Zo-1, Mucin 2 (Muc2), and E-cadherin. Used independently, BZA showed therapeutic effects comparable to those of infliximab (IFX). In addition, BZA modulated the abundance of gut microbiota especially Bifidobacterium pseudolongum, and influenced microbial metabolite production. Crucially, BZA's alleviation of DSS-induced colitis in mice was linked to change in gut microbiota composition, as evidenced by in vivo gut microbiota depletion and fecal microbiota transplantation (FMT) mice model. Molecularly, BZA inhibited STAT3 and NF-κB activation in DSS-induced colitis in mice. In general, BZA significantly reduced DSS-induced colitis in mice through modulating the gut microbiota and inhibiting STAT3 and NF-κB activation, and its independent use demonstrated a therapeutic potential comparable to IFX. This study highlights gut microbiota's role in IBD drug development, offering insights for BZA's future development and its clinical applications.

Scutellaria baicalensis Georgi alleviates Clostridium difficile associated diarrhea and its modulatory effects on the gut microbiota.

The growing incidence of Clostridium difficile associated diarrhea (CDAD) underscores the urgency for potent treatments. This research delves into the therapeutic potential of Scutellaria baicalensis Georgi (Lamiaceae) root (SR) in addressing CDAD and its influence on gut microbiota. Using a CDAD mouse model and fidaxomicin as a control, SR's impact was measured through diarrhea symptoms, colonic histopathology, and C. difficile toxin levels. Employing the PacBio platform, 16S rRNA full-length gene sequencing analyzed the gut microbial composition and the effect of SR. Results revealed SR considerably alleviated diarrhea during treatment and restoration phases, with a marked decrease in colonic inflammation. C. difficile toxin levels dropped significantly with SR treatment (P < 0.001). While SR didn't augment gut microbiota's overall abundance, it enhanced its diversity. It restored levels of Proteobacteria and Bacteroidetes, reduced Akkermansia spp. and Enterococcus spp. proportions, and modulated specific bacterial species' abundance. In essence, SR effectively mitigates CDAD symptoms, curtails inflammatory reactions, and beneficially restructures gut microbiota, suggesting its potential in advanced CDAD clinical intervention.

Carrier state of enterotoxigenic Escherichia coli virulence markers in pigs: effects on gut microbiota modulation and immune markers transcription.

Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in pigs at early age, leading to high mortality rates and significant economic losses in the swine industry. ETEC effect on gut microbiota and immune system is mostly studied in diarrheic model under controlled laboratory conditions, however its impact on asymptomatic carriers remains unknown. Thus, we investigated whether ETEC can modulate gut microbiota or regulate the transcription of immune markers in asymptomatic pigs in farm environment. Stool samples from newborn piglets, nursery and growing pigs, and sows were screened for ETEC markers, then submitted to 16S-rDNA sequencing to explore gut microbiota composition in carriers (ETEC+) and non-carriers (ETEC-) animals. We observed a reduced α-diversity in ETEC+ animals (p<0.05), while bacterial compositions were mostly driven by ageing (p>0.05). Prevotella marked ETEC-carrier group, while Rikenellaceae RC9 gut group was a marker for a healthy gut microbiota, suggesting being biomarker candidates for surveillance and supplementation purposes. Furthermore, we observed transcription regulation of il6 and tff2 genes in ETEC+ in newborn and nursery stages, respectively. Our findings indicate that ETEC presence modulate gut microbiota and the immune response in asymptomatic pigs; nevertheless, further studies using a probabilistic design must be performed to assess the effect of ETEC presence on gut imbalance in pigs despite the age bias.

Fecal Microbiota Transplantation Improves Clinical Symptoms of Fibromyalgia: An open-label, Randomized, Nonplacebo-Controlled Study.

Fibromyalgia (FM) is a complex and poorly understood disorder characterized by chronic and widespread musculoskeletal pain, of which the etiology remains unknown. Now, the disorder of the gut microbiome is considered as one of the main causes of FM. This study was aimed to investigate the potential benefits of fecal microbiota transplantation (FMT) in patients with FM. A total of 45 patients completed this open-label randomized, nonplacebo-controlled clinical study. The Numerical Rating Scale (NRS) scores in the FMT group were slightly lower than the control group at 1 month (P> 0.05), and they decreased significantly at 2, 3, 6, and 12 months after treatment (P < 0.001). Besides, compared with the control group, the Widespread Pain Index (WPI), Symptom Severity (SS), Hospital Anxiety and Depression Scale (HADS) and Pittsburgh Sleep Quality Index (PSQI) scores were significantly lower in the FMT group at different time points (P < 0.001). After 6 months of treatment, there was a significant increase in serotonin (5-HT) and gamma-aminobutyric acid (GABA) levels (P < 0.001), while glutamate levels significantly decreased in the FMT group (P < 0.001). The total effective rate was higher in the FMT group (90.9%) compared to the control group (56.5%) after 6 months of treatment (P < 0.05). FMT can effectively improve the clinical symptoms of FM. With the close relations between the changes of neurotransmitters and FM, certain neurotransmitters may serve as a diagnostic marker or potential target for FM patients. PERSPECTIVE: Fecal microbiota transplantation (FMT) is a novel therapy that aims to restore the gut microbial balance and modulate the gut-brain axis. It is valuable to further explore the therapeutic effect of FMT on FM. Furthermore, certain neurotransmitters may become a diagnostic marker or a new therapeutic target for FM patients.

Alterations in the fecal microbiota of methamphetamine users with bad sleep quality during abstinence.

BACKGROUND: Methamphetamine (MA) abuse has resulted in a plethora of social issues. Sleep disturbance is a prominent issue about MA addiction, which serve as a risk factor for relapse, and the gut microbiota could play an important role in the pathophysiological mechanisms of sleep disturbances. Therefore, improving sleep quality can be beneficial for treating methamphetamine addiction, and interventions addressing the gut microbiota may represent a promising approach. METHOD: We recruited 70 MA users to investigate the associations between sleep quality and fecal microbiota by the Pittsburgh Sleep Quality Index (PSQI), which was divided into MA-GS (PSQI score < 7, MA users with good sleep quality, n = 49) and MA-BS group (PSQI score ≥ 7, MA users with bad sleep quality, n = 21). In addition, we compared the gut microbiota between the MA-GS and healthy control (HC, n = 38) groups. 16S rRNA sequencing was applied to identify the gut bacteria. RESULT: The study revealed that the relative abundances of the Thermoanaerobacterales at the order level differed between the MA-GS and MA-BS groups. Additionally, a positive correlation was found between the relative abundance of the genus Sutterella and daytime dysfunction. Furthermore, comparisons between MA users and HCs revealed differences in beta diversity and relative abundances of various bacterial taxa. CONCLUSION: In conclusion, the study investigated alterations in the gut microbiota among MA users. Furthermore, we demonstrated that the genus Sutterella changes may be associated with daytime dysfunction, suggesting that the genus Sutterella may be a biomarker for bad sleep quality in MA users.

New insights into the interactions between the gut microbiota and the inflammatory response to ulcerative colitis in a mouse model of dextran sodium sulfate and possible mechanisms of action for treatment with PE&AFWE.

BACKGROUND: Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation. Intestinal innate immunity, including innate immune cells, defends against pathogens and excessive entry of gut microbiota, while preserving immune tolerance to resident intestinal microbiota, and may be characterized by its capacity to produce a rapid and nonspecific reaction. The association between microbiota dysbiosis and the pathogenesis of IBD is complex and dynamic. When the intestinal ecosystem is in dysbiosis, the reduced abundance and diversity of intestinal gut microbiota make the host more vulnerable to the attack of exogenous and endogenous pathogenic gut microbiota. The aim of our study was to comprehensively assess the relationship between microbial populations within UC, the signaling pathways of pathogenic gut microbe therein and the inflammatory response, as well as to understand the effects of using PE&AFWE (poppy extract [Papaver nudicaule L.] and Artemisia frigida Willd. extract) on UC modulation. METHODS: A UC mouse model was established by inducing SPF-grade C57BL/6 mice using dextrose sodium sulfate (DSS). Based on metagenomic sequencing to characterize the gut microbiome, the relationship between gut microbiota dysbiosis and gut microbiota was further studied using random forest and Bayesian network analysis methods, as well as histopathological analysis. RESULTS: (1) We found that the 5 gut microbiota with the highest relative abundance of inflammatory bowel disease UC model gut microbiota were consistent with the top 5 ranked natural bacteria. There were three types of abundance changes in the model groups: increases (Chlamydiae/Proteobacteria and Deferribacteres), decreases (Firmicutes), and no significant changes (Bacteroidetes). The UC model group was significantly different from the control group, with 1308 differentially expressed species with abundance changes greater than or equal to 2-fold. (2) The proportion of the fecal flora in the UC group decreased by 37.5% in the Firmicutes and increased by 14.29% in the proportion of Proteobacteria compared to the control group before treatment. (3) The significantly enriched and increased signaling pathways screened were the 'arachidonic acid metabolic pathway' and the 'phagosomal pathway', which both showed a decreasing trend after drug administration. (4) Based on the causal relationship between different OTUs and the UC model/PE&AFWE administration, screening for directly relevant OTU networks, the UC group was found to directly affect OTU69, followed by a cascade of effects on OTU12, OTU121, OTU93, and OTU7, which may be the pathway of action that initiated the pathological changes in normal mice. (5) We identified a causal relationship between common differentially expressed OTUs and PE&AFWE and UC in the pre- and post-PE&AFWE-treated groups. Thereby, we learned that PE&AFWE can directly affect OTU90, after which it inhibits UC, inhibiting the activity of arachidonic acid metabolic pathway by affecting OTU118, which in turn inhibits the colonization of gut microbiota by OTU93 and OTU7. (6) Histopathological observation and scoring (HS) of the colon showed that there was a significant difference between the model group and the control group (p < 0.001), and that there was a significant recovery in both the sulfasalazine (SASP)and the PE&AFWE groups after the administration of the drug (p < 0.0001). CONCLUSION: We demonstrated causal effects and inflammatory metabolic pathways in gut microbiota dysbiosis and IBD, with five opportunistic pathogens directly contributing to IBD. PE&AFWE reduced the abundance of proteobacteria in the gut microbiota, and histopathology showed significant improvement.

Linking growth performance and carcass traits with enterotypes in Muscovy ducks.

Objective: Enterotypes (ETs) are the clustering of gut microbial community structures, which could serve as indicators of growth performance and carcass traits. However, ETs have been sparsely investigated in waterfowl. The objective of this study was to identify the ileal ETs and explore the correlation of the ETs with growth performance and carcass traits in Muscovy ducks. Methods: A total of 200 Muscovy ducks were randomly selected from a population of 5,000 ducks at 70-day old, weighed and slaughtered. The growth performance and carcass traits, including body weight, dressed weight and evidenced weight, dressed percentage, percentage of apparent yield, breast muscle weight, leg muscle weight, percentage of leg muscle and percentage of breast muscle, were determined. The contents of ileum were collected for the isolation of DNA and 16S rRNA gene sequencing. The ETs were identified based on the 16S rRNA gene sequencing data and the correlation of the ETs with growth performance and carcass traits was performed by Spearman correlation analysis. Results: Three ETs (ET1, ET2, and ET3) were observed in the ileal microbiota of Muscovy ducks with significant differences in number of features and α-diversity among these ETs (P < 0.05). Streptococcus, Candida Arthritis, and Bacteroidetes were the presentative genus in ET1 to ET3, respectively. Correlation analysis revealed that Lactococcus and Bradyrhizobium were significantly correlated with percentage of eviscerated yield and leg muscle weight (P < 0.05) while ETs were found to have a close association with percentage of eviscerated yield, leg muscle weight, and percentage of leg muscle in Muscovy ducks. However, the growth performance of ducks with different ETs did not show significant difference (P > 0.05). Lactococcus were found to be significantly correlated with leg muscle weight, dressed weight, and percentage of eviscerated yield. Conclusion: Our findings revealed a substantial variation in carcass traits associated with enterotypes in Muscovy ducks. It is implied that ETs might have the potential to serve as a valuable biomarker for assessing duck carcass traits. It would provide novel insights into the interaction of gut microbiota with growth performance and carcass traits of ducks.

Evaluating the therapeutic potential of moxibustion on polycystic ovary syndrome: a rat model study on gut microbiota and metabolite interaction.

Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion's impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites.

Integrated analysis of gut metabolome, microbiome, and exfoliome data in an equine model of intestinal injury.

BACKGROUND: The equine gastrointestinal (GI) microbiome has been described in the context of various diseases. The observed changes, however, have not been linked to host function and therefore it remains unclear how specific changes in the microbiome alter cellular and molecular pathways within the GI tract. Further, non-invasive techniques to examine the host gene expression profile of the GI mucosa have been described in horses but not evaluated in response to interventions. Therefore, the objectives of our study were to (1) profile gene expression and metabolomic changes in an equine model of non-steroidal anti-inflammatory drug (NSAID)-induced intestinal inflammation and (2) apply computational data integration methods to examine host-microbiota interactions. METHODS: Twenty horses were randomly assigned to 1 of 2 groups (n = 10): control (placebo paste) or NSAID (phenylbutazone 4.4 mg/kg orally once daily for 9 days). Fecal samples were collected on days 0 and 10 and analyzed with respect to microbiota (16S rDNA gene sequencing), metabolomic (untargeted metabolites), and host exfoliated cell transcriptomic (exfoliome) changes. Data were analyzed and integrated using a variety of computational techniques, and underlying regulatory mechanisms were inferred from features that were commonly identified by all computational approaches. RESULTS: Phenylbutazone induced alterations in the microbiota, metabolome, and host transcriptome. Data integration identified correlation of specific bacterial genera with expression of several genes and metabolites that were linked to oxidative stress. Concomitant microbiota and metabolite changes resulted in the initiation of endoplasmic reticulum stress and unfolded protein response within the intestinal mucosa. CONCLUSIONS: Results of integrative analysis identified an important role for oxidative stress, and subsequent cell signaling responses, in a large animal model of GI inflammation. The computational approaches for combining non-invasive platforms for unbiased assessment of host GI responses (e.g., exfoliomics) with metabolomic and microbiota changes have broad application for the field of gastroenterology. Video Abstract.

Quinic acid regulated TMA/TMAO-related lipid metabolism and vascular endothelial function through gut microbiota to inhibit atherosclerotic.

BACKGROUND: Quinic acid (QA) and its derivatives have good lipid-lowering and hepatoprotective functions, but their role in atherosclerosis remains unknown. This study attempted to investigate the mechanism of QA on atherogenesis in Apoe-/- mice induced by HFD. METHODS: HE staining and oil red O staining were used to observe the pathology. The PCSK9, Mac-3 and SM22a expressions were detected by IHC. Cholesterol, HMGB1, TIMP-1 and CXCL13 levels were measured by biochemical and ELISA. Lipid metabolism and the HMGB1-SREBP2-SR-BI pathway were detected by PCR and WB. 16 S and metabolomics were used to detect gut microbiota and serum metabolites. RESULTS: QA or low-frequency ABX inhibited weight gain and aortic tissue atherogenesis in HFD-induced Apoe-/- mice. QA inhibited the increase of cholesterol, TMA, TMAO, CXCL13, TIMP-1 and HMGB1 levels in peripheral blood of Apoe-/- mice induced by HFD. Meanwhile, QA or low-frequency ABX treatment inhibited the expression of CAV-1, ABCA1, Mac-3 and SM22α, and promoted the expression of SREBP-1 and LXR in the vascular tissues of HFD-induced Apoe-/- mice. QA reduced Streptococcus_danieliae abundance, and promoted Lactobacillus_intestinalis and Ileibacterium_valens abundance in HFD-induced Apoe-/- mice. QA altered serum galactose metabolism, promoted SREBP-2 and LDLR, inhibited IDOL, FMO3 and PCSK9 expression in liver of HFD-induced Apoe-/- mice. The combined treatment of QA and low-frequency ABX regulated microbe-related Glycoursodeoxycholic acid and GLYCOCHENODEOXYCHOLATE metabolism in HFD-induced Apoe-/- mice. QA inhibited TMAO or LDL-induced HCAECs damage and HMGB1/SREBP2 axis dysfunction, which was reversed by HMGB1 overexpression. CONCLUSIONS: QA regulated the gut-liver lipid metabolism and chronic vascular inflammation of TMA/TMAO through gut microbiota to inhibit the atherogenesis in Apoe-/- mice, and the mechanism may be related to the HMGB1/SREBP2 pathway.

Distinct members of the Caenorhabditis elegans CeMbio reference microbiota exert cryptic virulence that is masked by host defense.

Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. Understanding the ability of each distinct community member to promote or impair host health, alone or in the context of the community, is imperative for understanding how differences in community structure affect host health and vice versa. Recently, a reference 12-member microbiota for the model organism Caenorhabditis elegans, known as CeMbio, was defined. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh-WNT, and HLH-30/TFEB pathways. Although distinct CeMbio members differed in their ability to activate the PMK-1/p38 pathway, the ability to do so did not correlate with bacterial-induced lifespan reduction in wild-type or immunodeficient animals. In contrast, most species activated HLH-30/TFEB and showed virulence toward hlh-30-deficient animals. These results suggest that the microbiota of C. elegans is rife with bacteria that can shorten the host's lifespan if host defense is compromised and that HLH-30/TFEB is a fundamental and key host protective factor.

Impact of essential and optional ingredients on microbial and metabolic profiles of kimchi.

This study aimed to examine the impacts of essential and optional ingredients on the microbial and metabolic profiles of kimchi during 100 days of fermentation, using a mix-omics approach. Kimchi manufactured without essential ingredients (e.g., red pepper, garlic, ginger, green onion, and radish) had lower lactic acid content. The absence of garlic was associated with a higher proportion of Latilactobacillus and Lactococcus, while the absence of red pepper was associated with a greater proportion of Leuconostoc than the control group. In addition, red pepper and garlic served as primary determinants of the levels of organic acids and biogenic amines. Sugar was positively correlated with the levels of melibiose, and anchovy sauce was positively correlated with the levels of amino acids such as methionine, leucine, and glycine. These findings contribute to a fundamental understanding of how ingredients influence kimchi fermentation, offering valuable insights for optimizing kimchi production to meet various preferences.

Jian Gan powder ameliorates immunological liver injury in mice by modulating the gut microbiota and metabolic profiles.

BACKGROUND: Immunological liver injury (ILI) is a common liver disease associated with the microbiota-gut-liver axis. Jian Gan powder (JGP) exhibits both protective and therapeutic effects on hepatitis virus-induced ILI in the clinic. However, the underlying mechanisms remain elusive. The aim of this study is to investigate the hepatoprotective effects and associated mechanisms of JGP in the context of gut microbiota, utilizing a mouse model of ILI. METHODS: The mouse model was established employing Bacillus Calmette-Guérin (BCG) plus lipopolysaccharide (LPS). Following treatment with JGP (7.5, 15, or 30 g/kg), serum, liver, and fresh fecal samples were analyzed. 16S rRNA gene sequencing and untargeted metabolomics profiling were performed to assess the role of JGP on the gut microbiota and its metabolites. RESULTS: JGP treatment markedly reduced serum IFN-γ, IL-6, IL-22, and hepatic p-STAT3 (phosphorylated transducer and activator of transcription-3) expression. In contrast, JGP increased the percentage of proliferating cell nuclear antigen-positive liver cells in treated mice. Fecal 16S rRNA gene sequencing revealed that JGP treatment restored the levels of Alloprevotella, Burkholderia-Caballeronia-Paraburkholderia, Muribaculum, Streptococcus, and Stenotrophomonas. Additionally, metabolomics analysis of fecal samples showed that JGP restored the levels of allylestrenol, eplerenone, phosphatidylethanolamine (PE) (P-20:0/0:0), sphingomyelin (SM) d27:1, soyasapogenol C, chrysin, and soyasaponin I. CONCLUSIONS: JGP intervention improves ILI by restoring gut microbiota and modifying its metabolic profiles. These results provide a novel insight into the mechanism of JGP in treating ILI and the scientific basis to support its clinical application.