OBJECTIVE:This study aimed to investigate the mechanism that Lactobacillus murinus (L. murinus) alleviated lung inflammation induced by polycyclic aromatic hydrocarbons (PAHs) exposure based on metabolomics. METHODS:Female mice were administrated with PAHs mix, L. murinus and indoleacrylic acid (IA) or indolealdehyde (IAId). Microbial diversity in feces was detected by 16 S rRNA gene sequencing. Non-targeted metabolomics analysis in urine samples and targeted analysis of tryptophan metabolites in serum by UPLC-Orbitrap-MS and short-chain fatty acids (SCFA) in feces by GC-MS were performed, respectively. Flow cytometry was used to determine T helper immune cell differentiation in gut and lung tissues. The levels of IgE, IL-4 and IL-17A in the bronchoalveolar lavage fluid (BALF) or serum were detected by ELISA. The expressions of aryl hydrocarbon receptor (Ahr), cytochrome P450 1A1 (Cyp1a1) and forkheadbox protein 3 (Foxp3) genes and the histone deacetylation activity were detected by qPCR and by ELISA in lung tissues, respectively. RESULTS:PAHs exposure induced lung inflammation and microbial composition shifts and tryptophan metabolism disturbance in mice. L. murinus alleviated PAHs-induced lung inflammation and inhibited T helper cell 17 (Th17) cell differentiation and promoted regulatory T cells (Treg) cell differentiation. L. murinus increased the levels of IA and IAId in the serum and regulated Th17/Treg imbalance by activating AhR. Additionally, L. murinus restored PAHs-induced decrease of butyric acid and valeric acid which can reduce the histone deacetylase (HDAC) level in the lung tissues, enhancing the expression of the Foxp3 gene and promoting Treg cell differentiation. CONCLUSION:our study illustrated that L. murinus alleviated PAHs-induced lung inflammation and regulated Th17/Treg cell differentiation by regulating host tryptophan metabolism and SCFA levels. The study provided new insights into the reciprocal influence between gut microbiota, host metabolism and the immune system, suggesting that L. murinus might have the potential as a novel therapeutic strategy for lung diseases caused by environmental pollution in the future.

Developing ultrasensitive sensing platforms for trace ochratoxin A (OTA) in food safety is still challenging. Herein, we presented a novel dual-mode sensing strategy for fluorescence and colorimetric detection of OTA by combining the target-responsive hemin-encapsulated and copper nanoclusters (CuNCs) functionalized DNA hydrogel. Through simple assembly and in situ synthesis methods, fluorescence CuNCs are synthesized and modified on the 3D hydrophilic network structure of DNA cross-linked. OTA specifically recognized by Apt-linker can control the collapse of hydrogel, resulting in the fluorescence quenching of CuNCs and release of coated hemin. Interestingly, OTA could trigger Apt-linker conformational changes to form G-quadruplex structures, allowing the released hemin to form G-quadruplex/hemin DNAzyme via self-assembly. Fluorescence signal amplification could be achieved through further fluorescence quenching of CuNCs caused by DNAzymecatalyzed hydrogen peroxide (H2O2) because of the peroxidase activity of DNAzyme. Simultaneously, DNAzyme could catalyze the H2O2-mediated oxidation of TMB to provide colorimetric signal. Thereafter, the DNACuNCs hydrogel exhibited low detection limits of 3.49 pg/mL in fluorescence mode and 0.25 ng/mL in colorimetric modality. Real sample analyses of foodstuffs showed satisfactory results, providing prospective potential for monitoring mycotoxin contaminant.

Background and objectivesThe oral and gut microbiota play significant roles in childhood asthma pathogenesis. However, the communication dynamics and pathogenic mechanisms by which oral microbiota influence gut microbiota and disease development remain incompletely understood. This study investigated potential mechanisms by which oral-originated gut microbiota, specifically Prevotella genus, may contribute to childhood asthma etiology.MethodsOral swab and fecal samples from 30 asthmatic children and 30 healthy controls were collected. Microbiome composition was characterized using 16S rRNA gene sequencing and metagenomics. Genetic distances identified potential oral-originated bacteria in asthmatic children. Functional validation assessed pro-inflammatory properties of in silico predicted microbial mimicry peptides from enriched asthma-associated species. Fecal metabolome profiling combined with metagenomic correlations explored links between gut microbiota and metabolism. HBE cells treated with Prevotella bivia culture supernatant were analyzed for lipid pathway impacts using UPLC-MS/MS.ResultsChildren with asthma exhibited distinct oral and gut microbiota structures. Prevotella bivia, P. disiens, P. oris and Bacteroides fragilis were enriched orally and intestinally in asthmatics, while Streptococcus thermophilus decreased. P. bivia, P. disiens and P. oris in asthmatic gut likely originated orally. Microbial peptides induced inflammatory cytokines from immune cells. Aberrant lipid pathways characterized asthmatic children. P. bivia increased pro-inflammatory and decreased anti-inflammatory lipid metabolites in HBE cells.ConclusionThis study provides evidence of Prevotella transfer from oral to gut microbiota in childhood asthma. Prevotella’s microbial mimicry peptides and effects on lipid metabolism contribute to disease pathogenesis by eliciting immune responses. Findings offer mechanistic insights into oral-gut connections in childhood asthma etiology.

Both chromium picolinate (Cr-pic) and chromium trichloride (CrCl3) were used as dietary supplements in agricultural products and foodstuffs. We found either these two forms of Cr(III) could ameliorate inflammation and cholestasis in DDC-induced primary sclerosing cholangitis (PSC) mice via regulating bile acid metabolism. Although two Cr(III) are able to alleviate hepatic inflammation by reducing the aggregation of macrophage, Cr-pic exhibiting superior efficacy in decreasing M1 macrophages. Two Cr(III) show inconsistent in regulating intestinal Fxr, but Cr-pic could active intestinal Fxr, promoting intestinal barrier repair. Additionally, both Cr-pic and CrCl3 enhanced functional abundance of BSH enzymes involved in bile acid transformation, with Cr-pic seems to perturb the abundance of genus more than CrCl3. In conclusion, this study highlights the efficacy of Cr-pic and CrCl3 in mitigating inflammation and cholestasis in PSC, Cr-pic is expected superior than CrCl3 to be supplement ingredient used in PSC treatment via regulating bile acid metabolism.

The ubiquitous presence of Microplastics (MPs) in various environments documented in recent years has recently raised significant concerns about their toxic effects. While macrophages serve as the first line of defense against toxic substances and pathogens, the impact and mechanisms of microplastics on these immune cells remain unclear. This study aims to explore whether MPs induce macrophage apoptosis through the promotion of reactive oxygen species (ROS) generation and alterations in metabolic profiles. The viability of RAW264.7 cells decreased as the concentration of 0.5 µm or 5 µm MPs ranged from 0.2 to 1.5 mg/mL, with a more pronounced effect observed in the 0.5 µm MPs group. Zebrafish exposed to 0.5 µm or 5 µm MPs at a concentration of 0.5 mg/mL exhibited decreased macrophage abundance and increased apoptosis, accompanied by alterations in the expression of inflammatory and apoptosis-related genes. While 0.5 µm MPs were observed to enter macrophages, 5 µm MPs only adhered to the cell membrane surface. Both particle sizes induced ROS generation and disrupted cellular metabolism in RAW264.7 cells. Notably, macrophages exhibited a more pronounced response to 0.5 µm MPs, characterized by heightened ROS generation, increased secretion of pro-inflammatory mediators, and a significant decrease in sphingolipid metabolism. These findings suggest that the adverse effects on macrophages are greater with 0.5 µm MPs compared to 5 µm MPs, possibly attributed to particle size effects. This study contributes additional evidence on the impact of MPs on human immune cells.

In recent years, chromium (Cr) has been found to induce neurotoxicity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of chromium exposure on the metabolome and microbiome that may contribute to neurotoxicity in juvenile zebrafish. Zebrafish embryos were exposed to 1 mg/L Cr (III) and 1 mg/L Cr (VI) for 7 days, respectively. Swimming distance and locomotor behavior was decreased, and acetylcholinesterase activity was reduced in Cr-exposed groups. Total cholesterol levels were decreased in Cr-exposed groups. The differential-expressed metabolites due to Cr exposure were mainly enriched in primary bile acid biosynthesis, which indicated that Cr exposure may promote cholesterol conversion. The abundance of Bacteroidetes decreased and the abundance of Actinomycetes increased in Cr-exposed groups, as compared with that in the control group. At the genus level, the abundance of Acinetobacter, Acidophorax, Mycobacterium, Aeromonas, Hydrophagophaga, and Brevundimonas increased, whereas Chryseobacterium, Pseudomonas, Delftia, and Ancylobacter decreased in the Cr-exposed groups. Analysis of the correlation between gut microbiota and bile acid metabolites showed that changes of gut microbial community due to Cr exposure may be related to secondary bile acid metabolism. Collectively, chromium exposure may disturb cholesterol metabolism, including primary bile acid and microbiota-related secondary bile acid metabolism. This study provides potential mechanism of the effects of chromium on neurotoxicity based on modulation of metabolome and gut microbiota diversity, which needs further verification.

Introduction:Cold and humid environments alter the intestinal microbiota, and the role of the intestinal microbiota in the development of diarrhea associated with cold-dampness trapped spleen syndrome in Chinese medicine is unclear.Methods:The 30 mice were randomly divided into normal and model groups, with the model group being exposed to cold and humid environmental stresses for 7 days. Then, mouse intestinal contents were collected and analyzed their intestinal microbiota and digestive enzymes.Results:Our findings revealed significant increases in sucrase and lactase activities, as well as microbial activity, in the model group (p < 0.05). β-diversity analysis highlighted distinct intestinal microbiota compositions between the two groups. Specifically, the experimental group showed a unique dominance of the genera and strains Clostridium sensu stricto 1 and Clostridium sp. ND2. LEfSe analysis identified Helicobacter, Roseburia, and Eubacterium plexicaudatum ASF492 as differentially abundant species in them model group. Network analysis demonstrated that rare bacterial species mostly governed the microbial interactions, exhibiting increased mutual promotion. On the other hand, abundant species like Lactobacillus johnsonii and Lactobacillus reuteri showed mutual inhibitory relationships.Discussion:In summary, exposure to cold and humid conditions led to increased intestinal enzyme activities and a shift in microbial composition, favoring the growth of rare bacterial species. These changes suggest that rare bacteria in the intestinal microbiota play a critical role in the pathology of diarrhea associated with cold-dampness trapped spleen syndrome, revealing unique survival strategies among bacterial populations under stressful conditions.

Limosilactibacilus reuteri (L. reuteri) is a gram-positive probiotic that does not produce peroxidase. Certain strains of L. reuteri have been approved for use in human health products in China. The probiotic mechanism of L. reuteri in organisms can be divided into two directions: first, L. reuteri directly regulates the gut microbiota and indirectly affecting the host; second, L. reuteri secretes substances that directly affect the host. Numerous studies have shown that a deficiency in this commensal bacterium is associated with various diseases in different systems (such as inflammation in the digestive system, systemic lupus erythematosus in the autoimmune system, metabolic syndrome in the endocrine system, and mastitis in the reproductive system). However, although recent studies have found that L. reuteri can also promote disease progression, but overall, it is more beneficial than harmful in general. Further, more in-depth experiments are needed to determine whether L. reuteri should be removed from probiotics in the future. In this review, we provide an overview of the research history of L. reuteri and conclude with the main mechanisms through which this intestinal symbiont can improve health or aggravate diseases.

Current methods for the rapid detection of trace antibiotics in the environment remains problems of low accuracy and false negative or false positive, making the development of fast, and accurate, and reliable methods for antibiotic testing a major challenge that needs to be addressed. Herein, we developed a novel label-free colorimetric and fluorescent dual-mode aptasensor assembled by the strong interaction of layered MoSe2 nanosheets (MoSe2 NSs) with ampicillin (AMP) aptamer functionalized silver nanoclusters (Apt-AgNCs) that specifically bind AMP to allow the sensitive and selective detection of AMP. Apt-AgNCs could be adsorbed on the surface of MoSe2 NSs via van der Waals force to form a nanocomposite, Apt-AgNCs/MoSe2 NSs. Interestingly, Apt-AgNCs/MoSe2 NSs act together to construct dual mode aptasensor through modulation of the intrinsic peroxidase activity of MoSe2 NSs and the fluorescence of Apt-AgNCs. In the presence of AMP, Apt-AgNCs could specifically bind AMP, triggering desorption from the MoSe2 NSs surface, leading to a decrease in the peroxidase activity of the system with the recovery in Apt-AgNCs fluorescence. The dual-signal aptasensor exhibited good linear colorimetric and fluorescence responses in the AMP concentration ranges of 0.115-2.00 μM and 6-100 nM, respectively. Furthermore, the aptasensor was successfully measured AMP levels in commercially-bought milk and lake water with satisfactory results. Unlike single-signal aptasensors, the constructed dual-signal aptasensor could not only improve the detection precision, but also reduce the false positive or false negative results. These promising results suggest that the dual-readout strategy as demonstrated is general mode for the detection of other antibiotics or compounds using various aptamers functionalized AgNCs in concert with MoSe2 NSs.

Sulforaphane (SFN) is a promising phytochemical with a wide range of antitumor activities. A comprehensive understanding of the effects of SFN on breast cancer based on the metabolome and microbiome is limited. Thus, we treated MCF-7 cell-transplanted nude mice with 50 mg/kg SFN. SFN inhibits breast cancer cell proliferation. SFN increased the levels of sulfate-related metabolites and glutathione-related metabolites and decreased tryptophan metabolites and methyl-purine metabolites in urinary metabolic profile. SFN indirectly affected the activation of aryl hydrocarbon receptor by tryptophan metabolism. The ratio of SAM to methionine was decreased by SFN while the global DNA methylation was downregulated in tumor tissue. SFN decreased the sulfate-reducing bacterium Desulfovibrio, which is related to reduced methylation capacity, and increased the genus Lactobacillus related to tryptophan metabolites with antitumor activities. In conclusion, we provide a perspective on the metabolome and microbiome to elucidate the antitumor activities of SFN.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease characterized by inflammation and fibrosis of the bile ducts. Cholestasis may lead to hepatic inflammation and fibrosis, and amelioration of cholestasis may allow recovery from inflammatory and fibrotic pathological damage. Prevotella copri (P. copri) interventions have been reported to significantly improve cholestasis and liver fibrosis in 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced PSC mouse models. Even though P. copri treatment alone cannot bring about recovery from DDC-induced inflammation, it increases the abundance of Lactobacillus murinus (L. murinus) compared with DDC treatment, which has been reported to have anti-inflammatory effects. The abundance of L. murinus still not recovering to a normal level may underlie hepatic inflammation in P. copri + DDC mice. Separate or combined interventions of P. copri and L. murinus were used to investigate the molecular mechanism underlying the improvement in PSC inflammation and fibrosis. P. copri and L. murinus significantly reduced the hepatic inflammatory cell aggregation and inflammatory factor expression as well as the hepatic collagen content and fibrin factor expression in the PSC mice. Further analysis of phosphorylation and dephosphorylation levels revealed that treating the PSC mice with the P. copri and L. murinus combined intervention inhibited the activity of the DDC-activated TGF-β1/Smad pathway, thereby reducing liver inflammation and fibrosis. The combination of P. copri and L. murinus inhibits the TGF-β1/Smad pathway and reduces inflammation and fibrosis in PSC.

Intestinal microbiota disorder was associated with constipation. This study investigated the microbiota–gut–brain axis and oxidative stress mediated by intestinal mucosal microbiota in mice with spleen deficiency constipation. The Kunming mice were randomly divided into the control (MC) group and the constipation (MM) group. The spleen deficiency constipation model was established by gavage with Folium sennae decoction and controlled diet and water intake. The body weight, spleen and thymus index, 5-Hydroxytryptamine (5-HT) and Superoxide Dismutase (SOD) content were significantly lower in the MM group than the MC group, the content of vasoactive intestinal peptide (VIP) and malondialdehyde (MDA) content were significantly higher than the MC group. The Alpha diversity of intestinal mucosal bacteria was not changed but beta diversity was changed in mice with spleen deficiency constipation. Compared to the MC group, the relative abundance of Proteobacteria was an upward trend and the Firmicutes/Bacteroidota (F/B) value was a downward trend in the MM group. There was a significant difference in the characteristic microbiota between the two groups. In the MM group, Brevinema, Akkermansia, Parasutterella, Faecalibaculum, Aeromonas, Sphingobium, Actinobacillus, and other pathogenic bacteria were enriched. Meanwhile, there was a certain relationship between the microbiota and gastrointestinal neuropeptide and oxidative stress indicators. The community structure of intestinal mucosal bacteria in mice with spleen deficiency constipation was changed, which was characterized by the reduction of F/B value and enrichment of Proteobacteria. Microbiota–gut–brain axis may be important for spleen deficiency constipation.

Epidemiological studies have shown that PAHs may exert adverse effects on childhood asthma. However, the underlying molecular mechanism remains to be fully elucidated. This study aimed to investigate this process in view of metabolic pathways, especially one-carbon metabolism and tryptophan metabolism. Fifty asthmatic children and 50 control subjects were recruited for this study. Serum IgE and IL-17A levels were detected by ELISA. Serum PAH concentrations were measured by GC-MS. One-carbon-related metabolites and tryptophan metabolites were determined by UPLC-Orbitrap-MS. DNA methylation was analyzed by bisulfite sequencing PCR. ChIP assays were used to examine H3K4me3 enrichment on IL-17A gene. Multivariable linear regression was performed to evaluate the association between PAHs and childhood asthma mediated by intermediators. HE staining in lung tissue, IgE and IL-17A in BALF, metabolic profiles in urine, and Ahr, Il-17 alpha, and Cyp1a1 gene expression were determined in PAHexposed mice. Serum Fla level was associated with childhood asthma (OR = 1.380, 95% CI: 1.063-1.792), and had a great effect on one-carbon metabolites, especially SAH, SAM, and Ser, which exerted significant mediation effects on the relationship between the Fla concentration and asthma. Moreover, we did find significant mediation effects between serum Fla and asthma by LINE-1 DNA methylation and H3K4me3 levels in the IL-17A promoter region. The differential Trp metabolites, such as Trp, tryptamine, IA, IAA, indole, IAld, and IAAld, indicated that asthmatic children had increased indole-AhR pathway. Mediation analysis failed to show a mediator effect of Trp metabolites in the association between PAHs and childhood asthma. An animal study confirmed that PAH exposure increased methylation levels, and altered Trp metabolite-AhR-IL-17A axis, which may be influenced by gender. PAHs disturbed one-carbon metabolism to influence the methyl group refilling DNA methylation and histone methylation, and disturbed tryptophan metabolism to regulate Th17-cell differentiation, which may elevate serum IL-17A concentration in asthmatic children.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by bile duct inflammation, fibrosis, bile acid (BA) metabolism disorders and gut microbiota dysbiosis. At present, the aetiology and pathogenesis of PSC are not clear, and there is no specific or effective treatment available. Therefore, new research perspectives are needed to explore effective methods to treat PSC and improve symptoms. The intestinal microbiota of patients with PSC is known to be significantly different from that of healthy people. By comparing differentially abundant bacterial genera in PSC patients, it was found that the abundance of Prevotella copri (P. copri) was significantly decreased, suggesting that this species may have a protective effect against PSC disease. Therefore, comprehensively exploring the role and possible function of P. copri in the disease process is worthwhile. In this study, a PSC mouse model was established by feeding mice a customized diet supplemented with 0.1% (w/w) 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for one week, and the abundance of P. copri was confirmed to be decreased in this model. Previous studies in patients and animal models have demonstrated that gut microbiota intervention is an acceptable treatment for some diseases. We found that intervention with P. copri could significantly improve cholestasis and liver fibrosis by enhancing the FXR-related signalling pathway in PSC mice. Together, through the overall effect of P. copri on intestinal microbiota structure and its association with BAs, we speculate that P. copri intervention might be as potential biological treatment of PSC.

BACKGROUND:Recently, both trivalent chromium Cr (III) and hexavalent chromium Cr (VI) have been reported to produce neurotoxicity. However, the underlying mechanisms of the neurotoxicity caused by different chemical valence of chromium remain unclear. OBJECTIVE:The purpose of this study was to investigate the mechanism of neurotoxicity induced by exposure to chromium with different valence states based on metabolic disturbance in zebrafish larvae. METHODS:Zebrafish embryos were exposed to 1 mg/L Cr (III) and 1 mg/L Cr (VI) for 120 hpf respectively. The related indexes of neural development were observed by stereoscope and behavior analysis system. 8OH-dG were detected using enzyme-linked immunosorbent assay. The generation of reactive oxygen species was detected using an oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate. AChE activity was determined by a colorimetric assay based on hydrolysis of acetylcholine. The expression levels of neurodevelopmental genes and methyltransferase genes in juvenile zebrafish was analyzed by real-time PCR. The methylation status of neurogenin1 and neurod1 genes was detected by bisulfite sequencing PCR. The binding of H3K27me3 was detected by chromatin immunoprecipitation-qPCR. Metabolic profiles and one carbon metabolic analysis were performed by UPLC-MS. RESULTS:There were no significant differences in survival rate, hatching rate and spontaneous movement of zebrafish in both Cr-exposed groups compared to the control. The malformation rate in Cr (VI) -exposed group was obviously increased compared to the control and Cr (III) -exposed group. At 48hpf and 72hpf of exposure, the embryonic heart rate in Cr (III)-exposed group was significantly higher than that of Cr (VI)-exposed group and the control. At 120hpf, zebrafish in both Cr-exposed groups exhibited decreasing changes in swimming distance and disturbance of sensitivity to light and dark. 8OH-dG in Cr (VI)-exposed group were significantly higher than that in the control. The generation of ROS in both Cr -exposed groups was significantly higher than that in the control. The activity of AchE was significantly decreased in both Cr-exposed groups compared to the control. Most of early neurogenesis related genes, such as α-tubulin, elavl3, gap43, sox19b, neurogenin1 and neurod1 in Cr-exposed groups were significantly up-regulated compared to those in the control. The expression of dnmt1 and dnmt3 genes was significantly down-regulated in both Cr-exposed groups. BSP-PCR results showed that genic sequences in the neurogenin1 and neurod1 genes have lower levels of DNA methylation in both Cr-exposed groups, especial in Cr (VI)-exposed group. ChIP analysis showed that there was a decrease in H3K27me3 binding within the corresponding region of neurogenin1 in both Cr-exposed groups and that of neurod1 in Cr (III)-exposed group. Untargeted metabolomic analysis showed that significant changes in metabolites induced by Cr exposure were associated with differences in primary bile acid biosynthesis, phospholipid biosynthesis (phosphatidylcholine biosynthesis and phosphatidylethanolamine biosynthesis), linoleic acid metabolism, arachidonic acid metabolism, amino acid metabolism, purine metabolism, betaine metabolism, spermidine and spermine biosynthesis, and folate metabolism, the last four of which are related to one carbon metabolism. Targeted analysis of one carbon metabolites (5-MT, Gly, Met, SAH and Hcy) related with folate cycle and methionine metabolism were significantly decreased upon Cr exposure. The elevated SAM to SAH ratio in both Cr- exposed group indicated the decreasing capacity for methylation reaction. CONCLUSION:Cr (III) and Cr (VI) can induce neurotoxicity by interfering with one carbon metabolism and affecting DNA methylation and histone methylation to regulate the expression of neuro-related genes. Cr exposure also influenced primary bile acid biosynthesis and phospholipid biosynthesis, which are associated with neuroprotective effects and need to be further validated.

Background: Epigenetic mechanisms may play a role in which PAHs exert its adverse effects in childhood asthma. However, the underlying molecular mechanism remain to be fully elucidated. This study aimed to investigate this process in view of cellular metabolism, especially one carbon metabolism. Methods: Fifty asthmatic children and fifty control subjects were recruited in this study. Serum IgE and IL-17A was detected by ELISA assay. Serum PAHs levels were measured by GC-MS. One carbon-related metabolites were determined by UPLC-Orbitrap-MS. Blood DNA methylation in long interspersed nucleotide element-1 ( LINE-1 ) was analyzed by bisulfite sequencing PCR. ChIP assays were used to examine H3K4me3 modifications on IL-17A gene. Multivariable linear regression was performed to evaluate the associates between PAHs and DNA methylation and histone methylation mediated by one carbon metabolism. Results: The asthmatic group presented significantly higher total serum IgE and IL-17A levels. Serum Fla was associated with childhood asthma. The asthmatic group displayed a significantly decreasing in SAM abundance and a smaller but corresponding decrease in SAH, which indicated the increasing conversion from SAM to SAH and the elevated capacity of methylation reactions. Fla had a great effect on one carbon metabolites, especially SAH, SAM and Ser, which exerted significant mediation effects between the Fla level and asthma. What’s more, Fla had a positive effect on LINE-1 DNA methylation (β=0.395, P=0.000) and H3K4 tri-methylation level in the IL-17A promoter region(β=0.293, P=0.002). We did find significant mediation effect between serum Fla and asthma by LINE-1 DNA methylation and H3K4me3 level in the IL-17A promoter region. Conclusion: PAHs disturbed one carbon metabolism to influence the methyl group refill of DNA methylation and histone methylation, which may elevate serum IL-17A level in asthmatic children.

Microplastics (MPs) and tributyltin (TBT) are both potential environmental pollutants that enter organisms through the food chain and affect bodily functions. However, the effects and mechanisms of MPs and TBT exposure (especially the co-exposure of both pollutants) on mammals remain unclear. In this study, Ф5 μm MPs (5MP) was administered alone or in combination with TBT to investigate the health risk of oral exposure in mice. All three treatments induced inflammation in the liver, altered gut microbiota composition and disturbed fecal bile acids profiles. In addition to decreasing triglyceride (TG) and increasing aspartate aminotransferase (AST) and macrophage-expressed gene 1 (Mpeg1), 5MP induced hepatic cholestasis by stimulating the expression of the cholesterol hydroxylase enzymes CYP8B1 and CYP27A1, and inhibiting multidrug resistance-associated protein 2 and 3 (MRP2, MRP3), and bile-salt export pump (BSEP) to prevent bile acids for entering the blood and bile. Correspondingly, 5MP treatment decreased 7-ketolithocholic acid (7-ketoLCA) and taurocholic acid (TCA), which were positively correlated with decreased Bacteroides and Marvinbryantia and negatively correlated with increased Bifidobacterium. In addition, TBT increased interferon γ (IFNγ) and Mpeg1 levels to induce inflammation, accompanied by decreased 7-ketoLCA, tauro-alpha-muricholic acid (T-alpha-MCA) and alpha-muricholic acid (alpha-MCA) levels, which were negatively related to Coriobacteriaceae_UCG-002 and Bifidobacterium. Co-exposure to 5MP and TBT also decreased TG and induced bile acids accumulation in the liver due to inhibited BSEP, which might be attributed to the co-regulation of decreased T-alpha-MCA and Harryflintia. In conclusion, the administration of 5MP and TBT alone and in combination could cause gut microbiome dysbiosis and subsequently alter bile acids profiles, while the combined exposure of 5MP and TBT weakened the toxic effects of 5MP and TBT alone.

Tributyltin (TBT), an environmental pollutant widely used in antifouling coatings, can cause multiple-organ toxicity and gut microbiome dysbiosis in organisms, and can even cause changes in the host metabolomic profiles.

Evidence shows that urine has complex bacterial profiles with considerable variation between individuals. Aging and age-related conditions can lead to the changes to the composition of urine, which means that the available nutrition for bacteria in the bladder changes with age. We explored the characteristics of the urinary microbiota of elderly women and whether these are associated with age-related conditions such as diabetes and urinary tract infections. An elderly and a non-elderly cohort of women were included. Magnetic beads were used to isolate bacterial genomic DNA, which was analyzed based on the V3-V4 hypervariable region of the 16S rRNA gene. There were significant differences between the elderly and non-elderly regarding thirteen genera of bacteria. For example, the relative abundance of Lactobacillus was dramatically reduced in the elderly compared with the non-elderly; it also decreased with age in the elderly cohort and it was not correlated with urine pH. The relative abundance of Peptococcus increased with age in the elderly while the abundance of Bifidobacteria decreased with age. The abundance of Escherichia coli was the same in the two cohorts, and it increased with water intake and was not associated with urinary tract infection events. Higher levels of Lactobacillus (including Lactobacillus iners) in the elderly were associated with diabetes, and lower levels of Peptoniphilus and Dialister were correlated with asymptomatic bacteriuria. The urinary microbiota of women is affected by ageing, type 2 diabetes mellitus and asymtomatic bacteriuria.

Evidence shows urine specimens from different women have different populations of bacteria. The co-occurrence of hypertension and hyperlipidemia in those with diabetes may alter the composition of urine and the microenviroment of the bladder in which bacteria live. The aim of this study was to characterize the urinary microbiota in women with type 2 diabetes mellitus only and those with diabetes plus hypertension and/or hyperlipidemia, and to explore whether the composition of the urinary microbiota is affected by fasting blood glucose, blood pressure, and blood lipids. We enrolled 28 individuals with diabetes only, 24 with diabetes plus hypertension, 7 with diabetes plus hyperlipidemia, and 11 with diabetes plus both hypertension and hyperlipidemia. Modified midstream urine collection technique was designed to obtain urine specimens. Bacterial genomic DNA was isolated using magnetic beads and the urinary microbiota was analyzed using the Illumina MiSeq Sequencing System based on the V3-V4 hypervariable regions of the 16S rRNA gene. Among the four cohorts, the diabetes plus hypertension cohort had the highest relative abundance of Proteobacteria. In contrast, the diabetes plus hyperlipidemia cohort had the lowest relative abundance of Proteobacteria. In addition, Escherichia and Gardnerella were not found in the diabetes plus hyperlipidemia cohort but they were found in all of the other cohorts. Cetobacterium was only present in the diabetes plus hypertension cohort. The most abundant bacteria in the diabetes only and diabetes plus hyperlipidemia cohorts was Lactobacillus, while Prevotella was the most abundant bacteria in the diabetes plus hypertension and diabetes plus hypertension and hyperlipidemia cohorts. Moreover, the relative abundance of Lactobacillus was significantly lower in the diabetes plus hypertension cohort than in the diabetes only and diabetes plus hyperlipidemia cohorts. Several bacteria were correlated with the participants' fasting blood glucose, blood pressure, and blood lipids. In conclusion, hypertension and/or hyperlipidemia and other patient factors can affect the composition of the urinary microbiota in those with diabetes. The insights from this study could be used to develop microbiota-based treatment for comorbid conditions, including urinary tract infections, in those with diabetes.