Search Results (263)

Bisphenol analogs and their derivatives have been identified in human tissue and our living environment. There are major concerns over exposure to bisphenol analogs, especially the low-dose- and mixture-related toxicities, as they are considered potential endocrine-disrupting chemicals that may cause adverse effects in multiple organ systems. The liver is a critical organ responsible for an array of functions, e.g., metabolism, immunity, digestion, detoxification and vitamin storage, in addition to being a leading chemical target site. In this literature review of multiple species, we discussed the metabolism of bisphenol analogs in the liver, which was followed by discussions of bisphenol analog-induced liver toxicity in various species, including humans, rodents (mice and rats) and other species (chicken, pig, sheep, etc.). Further, the mechanisms of action and markers of liver damage such as oxidative stress, apoptosis, inflammation and fibrosis were discussed. It was concluded that bisphenol analogs can produce toxic effects on the liver in different species through various mechanisms, including epigenetic modifications and disruptions of the cell signaling pathways, gene expression, microbiome and metabolome. More research should be conducted to study the toxicity of bisphenol analogs other than bisphenol A and the underlying mechanisms of action, and in particular the potential for causing dysbiosis. Understanding the mechanisms of liver injury holds promise for improving the prediction of liver toxicity from bisphenol analogs and other environmental chemicals, and their risk assessment and legislation. Full article

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder whose precise etiology remains unclear, though growing evidence implicates gut microbiota in its pathogenesis. This study aimed to investigate the role of gut microbiota in the onset and progression of RA by employing fecal microbiota transplantation (FMT) in a collagen-induced arthritis (CIA) mouse model using DBA/1J and Aire⁻/⁻ strains. Mice received FMT from healthy donors, treatment-naïve RA patients, or treated RA patients in relapse, followed by assessment of microbiota composition via 16S rRNA sequencing, arthritis severity scoring, histological evaluations, and systemic inflammatory markers. The findings revealed distinct microbiota clustering patterns post-FMT across experimental groups, highlighting strain-specific colonization effects. Notably, genera such as Bifidobacterium and Paraprevotella correlated positively with arthritis severity in DBA/1J mice, whereas Corynebacterium, Enterorhabdus, and Odoribacter exhibited negative correlations, suggesting potential protective roles. Despite these microbial differences, minor variations in arthritis scores, paw inflammation, or systemic inflammation were observed among FMT groups. This indicates that although gut microbiota alterations are associated with RA pathogenesis, further investigation with larger cohorts and comprehensive sequencing approaches is essential to elucidate the therapeutic potential of microbiome modulation in autoimmune diseases. Full article

Hepatobiliary and gastrointestinal conditions, including chronic liver diseases and inflammatory bowel disease, are associated with significant morbidity and mortality globally. While the pathophysiology and symptoms vary from one disease to another, aberrations of the gut microbiome with deleterious microbial products affecting the intestinal barrier are common in patients suffering from these diseases. In this review, we summarize changes in the gut microbiome associated with various disease states and detail their role in gut barrier disruption and in modulating disease progression. Further, we discuss therapeutic interventions and precision medicine approaches targeting the microbiome, which have shown promise in alleviating these chronic illnesses in mouse models and patients. Full article

Slow-onset neurodegenerative disease in a low-expresser 2N4R P301L transgenic (Tg) mouse model is marked by neuroinflammation and by differing patterns of CNS deposition and accumulation of tau conformers, with such heterogeneities present even within inbred backgrounds. Gut microbial genotypes were notably divergent within C57BL6/Tac or 129SvEv/Tac congenic (Cg) sublines of TgTau^P301L mice, and these sublines differed when challenged with antibiotic treatment and fecal microbial transplantation. Whereas aged, transplanted Cg 129SvEv/Tac TgTau^P301L mice had neuroanatomical deposition of tau resembling controls, transplanted Cg C57BL6/Tac TgTau^P301L mice had different proportions of rostral versus caudal tau accumulation (p = 0.0001). These data indicate the potential for environmental influences on tau neuropathology in this model. Furthermore, Cg C57BL6/Tac TgTau^P301L cohorts differed from 129SvEv/Tac counterparts by showing 28% versus 9% net intercurrent loss (p = 0.0027). While the origin of this phenomenon is not established, it offers a parallel to differing patterns of frailty observed in C57BL6 versus 129 SvEv Tg mice expressing the 695 amino acid isoform of human amyloid precursor protein. We infer that generalized responses to protein aggregation might account for similar reductions in viability even when expressing different human proteins in the same inbred strain background. Full article

Background/Objectives: Esomeprazole, a proton pump inhibitor (PPI), is commonly prescribed for gastric-acid-related disorders but has been associated with impaired gastrointestinal (GI) motility with long-term use. However, the effect of concurrent antibiotic administration on this dysfunction remains unclear. Therefore, this study aimed to investigate the effects of antibiotics on esomeprazole-induced GI motility dysfunction and explore the underlying mechanisms in a mouse model. Methods: Male C57BL/6 mice were orally administered esomeprazole (160 mg/kg) five times per week for 4 weeks. Three days before initiating esomeprazole treatment, a broad-spectrum antibiotic cocktail (ABX) consisting of ampicillin (1 g/kg), neomycin (1 g/kg), metronidazole (1 g/kg), and vancomycin (0.5 g/kg) was provided in drinking water and maintained throughout the experimental period. Mosapride (3 mg/kg), a prokinetic agent, was used as a positive control. Results: Neither esomeprazole alone nor in combination with ABX affected body weight or food intake. Compared to normal controls, esomeprazole treatment significantly delayed both intestinal transit and gastric emptying. However, ABX co-administration further pronounced intestinal transit time and improved gastric motility. The potential mechanisms may involve interactions among gastric H⁺/K⁺-ATPase, CYP3A11, gastrointestinal hormones (secretin and motilin), and the gut microbiome. Conclusions: Long-term esomeprazole use can impair both gastric and intestinal motility, and ABX co-treatment further exacerbates intestinal transit delay while paradoxically enhancing gastric emptying. These findings highlight the critical role of the gut microbiota in esomeprazole-induced GI motility dysfunction and suggest that antibiotic use should be approached with caution, particularly when combined with PPI therapy. Full article

Background/Objectives: Exposure to high altitudes often results in gastrointestinal disorders. This study aimed to identify probiotic strains that can alleviate such disorders. Methods: We conducted a microbiome analysis to investigate the differences in gut microbiota among volunteers during the acute response and acclimatization phases at high altitudes. Subsequently, we established a mouse model of intestinal barrier damage induced by high-altitude exposure to further investigate the roles of probiotic strains and 2-ketoglutaric acid. Additionally, we performed untargeted metabolomics and transcriptomic analyses to elucidate the underlying mechanisms. Results: The microbiome analysis revealed a significant increase in the abundance of Faecalibacterium prausnitzii during the acclimatization phase. Faecalibacterium duncaniae (F. duncaniae) significantly mitigated damage to the intestinal barrier and the reduction of 2-ketoglutaric acid levels in the cecal contents induced by high-altitude exposure in mice. Immunohistochemistry and TUNEL staining demonstrated that high-altitude exposure significantly decreased the expression of ZO-1 and occludin while increasing apoptosis in ileal tissues. In contrast, treatment with F. duncaniae alleviated the loss of ZO-1 and occludin, as well as the apoptosis induced by high-altitude exposure. Furthermore, 2-ketoglutaric acid also mitigated this damage, reducing the loss of occludin and apoptosis in mice. Transcriptomic analysis indicated that high-altitude exposure significantly affects the calcium signaling pathway; conversely, the administration of F. duncaniae significantly influenced the PPAR signaling pathway, mineral absorption, and the regulation of lipolysis in adipocytes. Additionally, the expression of the FBJ osteosarcoma oncogene (Fos) was markedly reduced following the administration of F. duncaniae. Conclusions: F. duncaniae mitigates hypoxia-induced intestinal barrier damage by increasing levels of 2-ketoglutaric acid and shows promise as a probiotic, ultimately aiding travelers in adapting to high-altitude environments. Full article

Background: The human microbiome plays a crucial role in health and disease. Dysbiosis, an imbalance of microorganisms, has been implicated in cancer development and treatment response, including in primary brain tumors and brain metastases, through interactions mediated by the gut–brain axis. This scoping review synthesizes current evidence on the relationship between the human microbiome and brain tumors. Methods: A systematic search of five electronic databases was conducted by an expert librarian, using controlled vocabulary and keywords. A targeted grey literature search in Google Scholar and clinical trial registries was also undertaken. Eligible studies included primary research involving human patients, or in vivo, or in vitro models of glioma or brain metastasis, with a focus on the microbiome’s role in tumor development, treatment response, and outcomes. Results: Out of 584 citations screened, 40 studies met inclusion criteria, comprising 24 articles and 16 conference abstracts. These included 12 human studies, 16 using mouse models, 7 combining both, and 5 employing large datasets or next-generation sequencing of tumor samples. Thirty-one studies focused on primary brain tumors, six on brain metastases, and three on both. Of the 20 studies examining dysbiosis in tumor development, 95% (n = 19) found an association with tumor growth. Additionally, 71.4% (n = 5/7) of studies reported that microbiome alterations influenced treatment efficacy. Conclusions: Although the role of the gut–brain axis in brain tumors is still emerging and is characterized by heterogeneity across studies, existing evidence consistently supports a relationship between the gut microbiome and both brain tumor development and treatment outcomes. Full article

Background/Objectives: Lactiplantibacillus plantarum DSW3805 was isolated from Korean kimchi samples to examine its effect in a dextran sulfate sodium (DSS)-induced mouse model. Methods: To induce colitis, mice were treated with DSS for one week before sacrifice (n = 8 per group, total n = 40). Lacticaseibacillus rhamnosus GG (10⁹ CFU/day) or probiotics (L. plantarum DSW3805; 10⁸ or 10⁹ CFU/day) were administered for two weeks. To assess colitis damage, we evaluated the disease activity index, colon tissue, inflammatory factors, the microbiome, short-chain fatty acids, and intestine-related factors. Results: DSS induced colonic tissue damage (colon length, mucus thickness, and colonic crypts), and L. plantarum DSW3805 alleviated the tissue damage. Induced inflammation was reduced by inhibiting TNF-α, IFN-γ, IL-1β, IL-6, IgA, IgG, LTB4, PGE2, and NF-κB protein expression. The ratio of Firmicutes to Bacteroidetes in the PC group (DSS-treated control) was lower than that in the NC (DSS-nontreated control); L. plantarum DSW3805 increased the ratio. Higher concentrations of acetic, propionic, and butyric acids were detected in probiotic groups. In addition, harmful factors, such as calprotectin and β-glucuronidase, were reduced in the probiotic groups. Conclusions: L. plantarum DSW3805 alleviates gut damage by colitis; therefore, it can be used as a functional food to improve gut health. Full article

Air pollution has been widely recognized as a risk factor for neurological disorders, and the gut microbiome may play a mediating role. However, current evidence remains limited. In this study, a mouse model was employed with continuous exposure to real-time air pollution from conception to late adolescence. Effects of growth-stage air pollution exposure on the gut microbiome, host metabolites, and brain tissue were assessed. Pathological damage in the hippocampus and cortex was observed. Fecal metagenomic sequencing revealed alterations in both compositions and functions of the gut microbiome. Metabolic disturbances in unsaturated fatty acids and glycerophospholipids were identified in the intestine, serum, and brain tissues, with significant changes in metabolites (e.g., gamma-linolenic acid, alpha-linolenic acid, docosahexaenoic acid (DHA), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylserine (PS). Serum levels of the pro-inflammatory mediator leukotriene C4 were also elevated. Correlation analysis identified a group of different gut microbiome species that were associated with host metabolites. Furthermore, mediation analysis showed that intestinal and serum metabolites mediated the associations between the key gut microbiome and brain microbiome. These findings indicate that the metabolic crosstalk in the gut–brain axis mediates the neuronal damage in mice induced by growth-stage air pollution exposure, potentially through pathways involving lipid metabolism and inflammation. Full article

This study aimed to evaluate the therapeutic effect of Terminalia chebula (TC) on Tibetan yak-origin Salmonella-induced diarrhea and dysentery in mice. The levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), anti-inflammatory cytokines (IL-4 and IL-10), and the oxidative stress markers malondialdehyde (MDA), superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC), reduced glutathione (GSH-PX), and catalase (CAT) in the serum of mice were measured using ELISA kits. Using microbial diversity sequencing and non-targeted metabolomics detection techniques, the relevant mechanisms of TC treatment in a mouse Salmonella infection model were evaluated. The results showed the following: TC can effectively reduce the diarrhea rate; alleviate weight loss caused by Salmonella invasion; reduce the pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α in serum; and increase the concentrations of the anti-inflammatory cytokines IL-4 and IL-10. TC can improve the body’s antioxidant levels to heal the damage caused by oxidative stress and lipid peroxidation. The histological section results show that TC can significantly improve gastric and intestinal tissue lesions and has no toxic effects on the liver and kidneys. 16S rRNA and ITS sequencing analysis suggests that Lactobacillus, Enterorhabdus, Alistipes (bacterial community), Lodderomyces, Saccharomyces, and Penicillium (fungal community) may be key functional microbial communities in TC. Non-targeted metabolomics also suggests that the antibacterial treatment of dysentery with chebulic acid may be related to regulation of the Ras signaling pathway, long-term potentiation, the MAPK signaling pathway, metabolic pathways, and gut microbiome composition. Conclusion: TC has clear clinical efficacy in treating bacterial diarrhea, presenting anti-inflammatory and antioxidant effects. Its roles in regulating the gut microbiome and metabolic pathways and products were determined as the main reason for its therapeutic effect in a mouse gastroenteritis model caused by Salmonella infection. Full article

Ziziphi Spinosae Semen (ZSS), a homology of medicine and a type of seed, has been widely used to improve sleep quality. The present study aimed to assess the effects of ZSS flavonoid (ZSSF) extracted and isolated from ZSS on gut microbiota and hypothalamus metabolomic profiles in a chronic restraint stress (CRS)-induced anxiety mouse model. ZSSF was prepared using microporous resin chromatography, and seven compounds were determined by UPLC-MS. ZSSF treatment dramatically reduced anxiety-like behaviors, exerted sedative–hypnotic effects, increased hippocampal 5-HT and 5-HTP, and enhanced intestinal barrier function through inhibiting colon ZO-1, Claudin-1, and Occludin expression and reducing TNF-α, IL-6, and IL-1β levels. Compared with the CRS group, the diversity of gut microbiota in ZSSF-group mice was increased, with an increase in Bacteroidetes and a decrease in Firmicutes, and it was accompanied by an increase in fecal SCFAs. Hypothalamus metabolomics and lipidomics were performed to achieve 25 differential metabolites and 44 lipids, respectively. Serum metabolomics showed a total of 13 metabolites associated with anxiety were remarkably regulated by ZSSF. Weighted correlation network analysis (WGCNA) showed that glycerophospholipids (GPs) as well as phenylalanine, tyrosine, and L-tryptophan in peripheral and central parts were significant metabolites, which contributed to the pharmacological action of ZSSF. The mRNA expression of TPH2 and DDC key enzymes associated with tryptophan metabolism were upregulated, and PLA2G12A, LACT, and PLA2G6 key enzymes associated with GP metabolism were downregulated in ZSSF compared with CRS. Briefly, ZSSF improved tryptophan and GP metabolism and regulated the gut microbiome. This study may lay a theoretical basis for potentially developing ZSSF as a natural functional food ingredient for the improvement of anxiety and sleep disorders. Full article

Background/Objectives: Exposure to fine particulate matter (PM_2.5) causes significant respiratory and gastrointestinal health problems. In our prior research, we identified Lactobacillus acidophilus TW01 as a promising strain for mitigating oxidative damage, enhancing wound healing in intestinal epithelial cells, and protecting bronchial cells from cigarette smoke extract. Building upon these findings, this study examines the protective effects of this strain on lung damage induced by particulate matter (PM) through the gut–lung axis in mouse models. Methods: This study evaluated the protective effects of L. acidophilus TW01 against PM_2.5-induced lung injury using two in vivo mouse models (OVA sensitization combined with PM_2.5 exposure and DSS-induced colitis). Results: L. acidophilus TW01 exhibited significant protective effects in two in-vivo models, reducing pro-inflammatory cytokines (TNF-α, IL-6, and IL-5), modulating the immune response (IgG subtypes), and improving gut barrier integrity. Importantly, L. acidophilus TW01 increased the abundance of beneficial gut bacteria (Bifidobacterium and Lactobacillus). Conclusions: These findings highlight the significant protective/therapeutic potential of L. acidophilus TW01 in mitigating the adverse health effects of PM_2.5 exposure, emphasizing the interplay between the gut and lung microbiomes in overall health. The multi-faceted protective effects of this probiotic suggest a novel, multi-pronged therapeutic strategy for addressing the widespread health consequences of air pollution. Full article

Complement factor B (CFB) is a crucial component for the activation of the alternative pathway due to the formation of the C3 convertase with C3b, which further produces C3b to enhance the overall complement activity. Although Cfb is expressed not only in the immune tissues, but also in the reproductive tract, the physiological role of the alternative complement pathway in reproduction remains unclear. In this study, we addressed this issue by producing Cfb-knockout (KO) mice and analyzing their phenotypes. Sperm function, number of ovulated oocytes, and litter size were normal in KO mice. In contrast, the diversity of microbiomes in the gut and vaginal tract significantly increased in KO mice. Some serine protease activity in the serum from KO mice was lower than that of wild-type mice. Since the serum from KO mice showed significantly lower activity of the alternative complement pathway, CFB was found to be essential for this pathway. Our results indicate that although the alternative pathway is dispensable for normal fertility and development, it maintains the gut and vaginal microbiomes by suppressing their diversity and activating the alternative complement pathway. Full article

When conducting sequence-based analysis of microbiome samples, it is important to accurately represent the bacterial communities present. The aim of this study was to compare two commercially available DNA isolation and PCR amplification approaches to determine their impact on the taxonomic composition of microbiome samples following 16S rRNA gene sequencing. A well-established 16S rRNA gene profiling approach, which was widely used in the Human Microbiome Project (HMP), was compared with a novel alkaline degenerative technique that utilizes alkaline cell lysis in combination with a degenerate pool of primers for nucleic acid extraction and PCR amplification. When comparing these different approaches for the microbiome profiling of human and mouse fecal samples, we found that the alkaline-based method was able to detect greater taxonomic diversity. An in silico analysis of predicted primer binding against a curated 16S rRNA gene reference database further suggested that this novel approach had the potential to reduce population bias found with traditional methods, thereby offering opportunities for improved microbial community profiling. Full article

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disease driven by immune dysregulation. This study investigated the relationship between gut microbiota and lupus severity using the MRL/lpr lupus mouse model. Mice were grouped based on total immunoglobulin (Ig)G, IgG2a levels, and urine albumin-to-creatinine ratio (ACR), allowing for the comparison of gut microbiota profiles across different disease severities. Interestingly, severe lupus mice exhibited significant reductions in Ruminiclostridium cellulolyticum, Lactobacillus johnsonii, and Kineothrix alysoides, while Clostridium saudiense, Pseudoflavonifractor phocaeensis, and Intestinimonas butyriciproducens were enriched. These microbial shifts correlated with elevated IgG, IgG2a, and ACR levels, indicating that changes in the gut microbiome may directly influence key immunological markers associated with lupus severity. The depletion of beneficial species and the enrichment of potentially pathogenic bacteria appear to contribute to immune activation and disease progression. This study suggests that gut microbiota dysbiosis plays a critical role in exacerbating lupus by modulating immune responses, reinforcing the link between microbial composition and lupus pathogenesis. Our findings provide the first evidence identifying these distinct gut microbial species as potential contributors to lupus severity, highlighting their role as key factors in disease progression. Full article