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.

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.

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.

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.

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.

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.

The gut microbiota facilitate their host tolerance to extreme temperatures.

BACKGROUND: Exposure to extreme cold or heat temperature is one leading cause of weather-associated mortality and morbidity in animals. Emerging studies demonstrate that the microbiota residing in guts act as an integral factor required to modulate host tolerance to cold or heat exposure, but common and unique patterns of animal-temperature associations between cold and heat have not been simultaneously examined. Therefore, we attempted to investigate the roles of gut microbiota in modulating tolerance to cold or heat exposure in mice. RESULTS: The results showed that both cold and heat acutely change the body temperature of mice, but mice efficiently maintain their body temperature at conditions of chronic extreme temperatures. Mice adapt to extreme temperatures by adjusting body weight gain, food intake and energy harvest. Fascinatingly, 16 S rRNA sequencing shows that extreme temperatures result in a differential shift in the gut microbiota. Moreover, transplantation of the extreme-temperature microbiota is sufficient to enhance host tolerance to cold and heat, respectively. Metagenomic sequencing shows that the microbiota assists their hosts in resisting extreme temperatures through regulating the host insulin pathway. CONCLUSIONS: Our findings highlight that the microbiota is a key factor orchestrating the overall energy homeostasis under extreme temperatures, providing an insight into the interaction and coevolution of hosts and gut microbiota.

Role of imbalanced gut microbiota in promoting CRC metastasis: from theory to clinical application.

Metastasis poses a major challenge in colorectal cancer (CRC) treatment and remains a primary cause of mortality among patients with CRC. Recent investigations have elucidated the involvement of disrupted gut microbiota homeostasis in various facets of CRC metastasis, exerting a pivotal influence in shaping the metastatic microenvironment, triggering epithelial-mesenchymal transition (EMT), and so on. Moreover, therapeutic interventions targeting the gut microbiota demonstrate promise in enhancing the efficacy of conventional treatments for metastatic CRC (mCRC), presenting novel avenues for mCRC clinical management. Grounded in the "seed and soil" hypothesis, this review consolidates insights into the mechanisms by which imbalanced gut microbiota promotes mCRC and highlights recent strides in leveraging gut microbiota modulation for the clinical prevention and treatment of mCRC. Emphasis is placed on the considerable potential of manipulating gut microbiota within clinical settings for managing mCRC.

Association between gut microbiota and onset of type 2 diabetes mellitus: a two-sample Mendelian randomization study.

Aim: Mendelian randomization (MR) analysis has been used in the exploration of the role of gut microbiota (GM) in type 2 diabetes mellitus (T2DM); however, it was limited to the genus level. This study herein aims to investigate the relationship of GM, especially at the species level, with T2DM in order to provide some evidence for further exploration of more specific GM taxa and pathway abundance in T2DM. Methods: This two-sample MR study was based on the summary statistics of GM from the available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen consortium as well as the Dutch Microbiome Project (DMP), whereas the summary statistics of T2DM were obtained from the FinnGen consortium released data. Inverse variance weighted (IVW), MR-Egger, strength test (F), and weighted median methods were used to examine the causal association between GM and the onset of T2DM. Cochran's Q statistics was employed to quantify the heterogeneity of instrumental variables. Bonferroni's correction was conducted to correct the bias of multiple testing. We also performed reverse causality analysis. Results: The corrected IVW estimates suggested the increased relative abundance of family Oxalobacteraceae (OR = 1.0704) and genus Oxalobacter (OR = 1.0874), respectively, were associated with higher odds of T2DM, while that of species faecis (OR = 0.9460) had a negative relationship with T2DM. The relationships of class Betaproteobacteria, family Lactobacillaceae, species finegoldii, and species longum with T2DM were also significant according to the IVW results (all P < 0.05). Conclusions: GM had a potential causal association with T2DM, especially species faecis, finegoldii, and longum. Further studies are still needed to clarify certain results that are contradictory with previous findings.

Polyphenol Extracts from Ziziphus jujuba Mill. "Junzao" Attenuates Ulcerative Colitis by Inhibiting the NLRP3 and MAPKs Signaling Pathways and Regulating Gut Microbiota Homeostasis in Mice.

SCOPE: Polyphenols are the major active substances in red jujube fruit, and their anti-inflammatory and antioxidant activities suggest their potential utility in the prevention of ulcerative colitis (UC). METHODS AND RESULTS: In this study, the effect of polyphenol extracts from red jujube (Ziziphus jujuba Mill. "Junzao") (PERJ) on the dextron sulfate sodium (DSS)-induced UC mice is investigated. The result shows that PERJ effectively improves clinical symptoms, including food and water intake, the disease activity insex (DAI) and spleen index, and routine blood levels, and alleviates the shortening of the colon, in mice with DSS-induced UC. Meanwhile, PERJ remarkably decreases the expression of proinflammatory factors. Moreover, PERJ repairs intestinal barrier damage by increasing the expression level of mucin 2 and mucin 3, and the result is also confirmed in the histological assessment. Besides, the expression levels of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and mitogen-activated protein kinase cascade (MAPKs) signaling pathway-related proteins are inhibited by the PERJ administration. Finally, 16S rRNA sequencing analyses reveal that PERJ reverses intestinal microbiota dysbiosis by enhancing the abundance of Firmicutes and decreasing that of Proteobacteria and Bacteroidetes. CONCLUSION: PERJ probably inhibits the development of UC by suppressing the NLRP3 and MAPKs signaling pathways and regulating gut microbiota homeostasis, and can be considered as a potential resource for preventing UC.

Effects of Prevotella copri on insulin, gut microbiota and bile acids.

Obesity is becoming a major global health problem in children that can cause diseases such as type 2 diabetes and metabolic disorders, which are closely related to the gut microbiota. However, the underlying mechanism remains unclear. In this study, a significant positive correlation was observed between Prevotella copri (P. copri) and obesity in children (p = 0.003). Next, the effect of P. copri on obesity was explored by using fecal microbiota transplantation (FMT) experiment. Transplantation of P. copri. increased serum levels of fasting blood glucose (p < 0.01), insulin (p < 0.01) and interleukin-1ß (IL-1ß) (p < 0.05) in high-fat diet (HFD)-induced obese mice, but not in normal mice. Characterization of the gut microbiota indicated that P. copri reduced the relative abundance of the Akkermansia genus in mice (p < 0.01). Further analysis on bile acids (BAs) revealed that P. copri increased the primary BAs and ursodeoxycholic acid (UDCA) in HFD-induced mice (p < 0.05). This study demonstrated for the first time that P. copri has a significant positive correlation with obesity in children, and can increase fasting blood glucose and insulin levels in HFD-fed obese mice, which are related to the abundance of Akkermansia genus and bile acids.

Sialic acid-based probiotic intervention in lactating mothers improves the neonatal gut microbiota and immune responses by regulating sialylated milk oligosaccharide synthesis via the gut-breast axis.

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.

The effect of multiple sclerosis therapy on gut microbiota dysbiosis: a longitudinal prospective study.

Gut microbiota has complex immune functions, related to different pathologies, including multiple sclerosis (MS).This study evaluated the influence of treatments on gut microbiota in people with MS (PwMS). The research comprised 60 participants, including 39 PwMS and 21 healthy controls (HC). Among the PwMS, 20 were prescribed a disease-modifying therapy (DMT), either interferon beta1a or teriflunomide, while 19 received a combination of classical DMT and an immunoglobulin Y (IgY) supplement. For each participant, two sets of gut samples were collected: one at the study's outset and another after two months. Alpha and beta diversity analyses revealed no significant differences between groups. In comparison to the HC, the MS group exhibited an increase in Prevotella stercorea and a decrease in Faecalibacterium prausnitzii. Following treatment, individuals with MS showed enrichment in Lachnospiraceae and Streptococcus. The second sample, compared to the first one, demonstrated an increase in Bifidobacterium angulatum and a decrease in Oscillospira for individuals with MS. Gut microbiota diversity in PwMS is not significantly different to HC.However, specific taxonomic changes indicate the presence of a dysbiosis state. The use of DMTs and immunoglobulin Y supplements may contribute to alterations in microbial composition, potentially leading to the restoration of a healthier microbiome.

Exertional heat stroke-induced changes in gut microbiota cause cognitive impairment in mice.

BACKGROUND: The incidence of exertional heat stroke (EHS) escalates during periods of elevated temperatures, potentially leading to persistent cognitive impairment postrecovery. Currently, effective prophylactic or therapeutic measures against EHS are nonexistent. METHODS: The selection of days 14 and 23 postinduction for detailed examination was guided by TEM of neuronal cells and HE staining of intestinal villi and the hippocampal regions. Fecal specimens from the ileum and cecum at these designated times were analyzed for changes in gut microbiota and metabolic products. Bioinformatic analyses facilitated the identification of pivotal microbial species and metabolites. The influence of supplementing these identified microorganisms on behavioral outcomes and the expression of functional proteins within the hippocampus was subsequently assessed. RESULTS: TEM analyses of neurons, coupled with HE staining of intestinal villi and the hippocampal region, indicated substantial recovery in intestinal morphology and neuronal injury on Day 14, indicating this time point for subsequent microbial and metabolomic analyses. Notably, a reduction in the Lactobacillaceae family, particularly Lactobacillus murinus, was observed. Functional annotation of 16S rDNA sequences suggested diminished lipid metabolism and glycan biosynthesis and metabolism in EHS models. Mice receiving this intervention (EHS + probiotics group) exhibited markedly reduced cognitive impairment and increased expression of BDNF/TrKB pathway molecules in the hippocampus during behavioral assessment on Day 28. CONCLUSION: Probiotic supplementation, specifically with Lactobacillus spp., appears to mitigate EHS-induced cognitive impairment, potentially through the modulation of the BDNF/TrKB signaling pathway within the hippocampus, illustrating the therapeutic potential of targeting the gut-brain axis.

Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.