Search Results (132)

Background/Objectives: This study aimed to evaluate the effects of lung injury induced by insoluble uranium oxide particles on gut microbiota and related metabolites in rats. Methods: The rats were randomly divided into six UO₂ dose groups. A rat lung injury model was established through UO₂ aerosol. The levels of uranium in lung tissues were detected by ICP-MS. The expression levels of the inflammatory factors and fibrosis indexes were measured by enzyme-linked immunosorbent assay. Paraffin embedding-based hematoxylin & eosin staining for the lung tissue was performed to observe the histopathological imaging features. Metagenomic sequencing technology and HM700-targeted metabolomics were conducted in lung tissues. Results: Uranium levels in the lung tissues increased with dose increase. The expression levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Collagen I, and Hydroxyproline (Hyp) in rat lung homogenate increased with dose increase. Inflammatory cell infiltration and the deposition of extracellular matrix were observed in rat lung tissue post-exposure. Compared to the control group, the ratio of Firmicutes and Bacteroides in the gut microbiota decreased, the relative abundance of Akkermansia_mucinphila decreased, and the relative abundance of Bacteroides increased. The important differential metabolites mainly include αlpha-linolenic acid, gamma-linolenic acid, 2-Hydroxybutyric acid, Beta-Alanine, Maleic acid, Hyocholic acid, L-Lysine, L-Methionine, L-Leucine, which were mainly concentrated in unsaturated fatty acid biosynthesis, propionic acid metabolism, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, and other pathways in the UO₂ group compared to the control group. Conclusions: These findings suggest that uranium-induced lung injury can cause the disturbance of gut microbiota and its metabolites in rats, and these changes are mainly caused by Akkermansia_mucinphila and Bacteroides, focusing on unsaturated fatty acid biosynthesis and the propionic acid metabolism pathway. Full article

Sarcoidosis is a multi-organ, systemic disease of immunological origin. While its aetiology is unknown, it is believed to be influenced by genetic susceptibility, environmental factors, and autoimmunity. Recent research on the development and progression of sarcoidosis has focused increasingly on the role of microorganisms. Changes in the respiratory tract microbiome, and hence the physiology of the respiratory tract, are believed to influence the course of sarcoidosis; this is not unlikely, as research indicates that the state of the microbiota inhabiting individual ontocenoses, such as the intestines or blood, may be related to the health of the entire body. This review therefore discusses the microbiological factors that are believed to be involved in the development of the disease; however, as the aetiological factors of sarcoidosis are diverse and are based on highly complex mechanisms, our analysis is restricted to only the most likely factors. Full article

The COVID-19 pandemic has highlighted the complex interplay between the gut microbiota and systemic immune responses, particularly through the gut–lung axis. Disruptions in gut microbial diversity and function—commonly referred to as dysbiosis—have been increasingly implicated in the pathogenesis of SARS-CoV-2 infection. In this study, we assessed the gut bacteriome and permeability in SARS-CoV-2-infected patients using 16S sequencing and ELISA assays, respectively. We also measured blood inflammatory cytokines and fecal secretory IgA to evaluate systemic and mucosal immune responses. Significant alterations in both alpha and beta diversity metrics were observed in patients with COVID-19 (n = 79) and those with post-COVID-19 condition (n = 141) compared to the controls (n = 97). Differential abundance and taxonomic analyses revealed distinct microbial profiles in the infected groups. Increased plasma levels of IL-2, IL-6, IL-17A, IFN-γ, and zonulin were detected in patient samples. Some genera were elevated during acute infection, which was positively correlated with C-reactive protein, while Enterobacteriaceae and Escherichia-Shigella were associated with increased zonulin levels, indicating compromised intestinal barrier function. These findings suggest that gut dysbiosis may contribute to bacterial translocation and systemic inflammation. Overall, our results highlight the importance of the gut–lung axis and suggest that modulating the gut microbiota could support immune regulation in SARS-CoV-2 infection. Full article

The global prevalence of asthma is approximately 4.3%, and current asthma treatments focus on reducing symptoms, maintaining normal activity levels, and preventing the deterioration of lung function, rather than achieving a cure or complete prevention. We identified isochlorogenic acid C (ICGAC) as a potential natural medicine for the treatment of asthma. However, the bioavailability of ICGAC was low, ranging from 14.4% to 16.9%, suggesting the involvement of the gut microbiota. The full spectrum of ICGAC’s anti-asthmatic mechanism remains to be elucidated. This study investigated the mechanism by which ICGAC alleviates allergic asthma through the gut–lung axis. We discovered anti-asthma pathways and targets based on the selective regulation of lipid peroxidation and employed pharmacological tools to preliminarily validate their mechanisms and efficacy. To study the role of ICGAC in regulating the gut microbiota, we performed 16S rRNA gene sequencing and metabolite analysis. Furthermore, by combining molecular biology and lipid metabolomics, we elucidated the underlying anti-asthma mechanisms of ICGAC. The effective form of ICGAC varies between single and long-term administration. The oral administration of ICGAC enhances the gut-microbiota-derived production of short-chain fatty acids (SCFAs) as the active substances, modulates immune cell activity, influences the differentiation of T- and B-cells, and reduces airway inflammation. ICGAC also regulates the metabolic network of lipid mediators (LMs) and polyunsaturated fatty acids (PUFAs), thus exerting anti-inflammatory effects by modulating arachidonate lipoxygenase (ALOX) activity and LM levels. In addition, ICGAC enhanced the antioxidant response by upregulating the expression of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and nuclear factor erythroid 2-related factor 2 (Nrf2), while inhibiting the release of interleukin-4 (IL-4), thereby suppressing asthma inflammation and IgE production. The anti-asthmatic mechanism of oral ICGAC involves the inhibition of lipid peroxidation by chlorogenic acid (CGA) and SCFAs produced by the gut microbiota. ICGAC suppresses asthma-associated inflammatory and oxidative stress responses through the upregulation of GPX4, SLC7A11, and Nrf2 in lung tissue. This study not only provides a solid foundation for the potential clinical use of ICGAC in asthma treatment but also offers novel insights for future research and therapeutic strategies targeting asthma. Full article

COVID-19 presents a wide range of symptoms, including gastrointestinal manifestations such as diarrhea, nausea, and abdominal pain. Lactobacillus acidophilus has been proposed as a potential adjunct therapy to alleviate these symptoms due to its probiotic properties, which help restore gut microbiota balance and modulate immune responses. This review systematically analyzed studies assessing the effects of L. acidophilus in COVID-19 patients with gastrointestinal symptoms. The literature search was conducted through PubMed and the WHO COVID-19 database using keywords such as “Lactobacillus acidophilus”, “COVID-19”, “gastrointestinal symptoms”, and “inflammation markers”. The search covered studies published until February 2025. Inclusion criteria: observational and clinical trials with L. acidophilus for symptom relief. Exclusion: animal studies and non-ethical approvals. The findings suggest that L. acidophilus supplementation may contribute to faster resolution of diarrhea, improved gut microbiota balance, and reduced inflammatory markers. However, some studies have found no significant impact on hospitalization rates or disease progression. The probiotic’s mechanisms of action appear to involve microbiota modulation, intestinal barrier reinforcement, and anti-inflammatory effects rather than direct viral inhibition in COVID-19 after progression. Some L. acidophilus strains show promise, and clinical validation should follow careful preclinical studies (in vitro, cell lines, and animal models), especially in vulnerable populations such as immunocompromised individuals. Understanding the gut–lung axis and its role in immune response regulation, together with the need for a thorough characterization of the specific strains, including biochemical, genomic, and functional properties, before testing in humans, may provide deeper insights into the therapeutic potential of probiotics in viral infections. Full article

This review focuses on the potential health risks of artificial food additives, especially their effects on lung health. Preservatives, synthetic colorants, and flavor enhancers, which are commonly used in processed foods, play roles in worsening respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). These additives cause oxidative stress, systemic inflammation, and immune dysregulation, often through the gut-lung axis. The preservatives sodium nitrite and sulfites have the risk of causing bronchial hyper-responsiveness and allergic reactions. The synthetic colorant, Ponceau 4R, is also related to immune-mediated lung inflammation. Flavoring agents such as diacetyl contribute to occupational respiratory diseases like bronchiolitis obliterans. In animal models, prenatal exposure to additives, such as titanium dioxide (E171), might disrupt the development of respiratory neural networks, with long-term consequences. Ultra-processed foods (UPFs), which also contain a high concentration of additives, lead to systemic inflammation and impair lung function. Despite their wide usage, the use of these additives has become a warning sign due to their safety issue, particularly in sensitive people like children, pregnant women, and patients with pre-existing respiratory and chronic conditions. The review highlights the serious need for strict regulation and further research on the long-term effects of food additives on respiratory health. Policymakers should ban these food additives that are more harmful to human health. As an alternative to artificial additives, natural flavors and colors from fruits and vegetables, safe preservatives, and minimally processed ingredients can be used. Full article

Antibiotic resistance represents a growing public health threat, with airborne drug-resistant strains being especially alarming due to their ease of transmission and association with severe respiratory infections. The respiratory microbiome plays a pivotal role in maintaining respiratory health, influencing the dynamics of antibiotic resistance among airborne pathogenic microorganisms. In this context, this review proposes the exploration of the complex interplay between the respiratory microbiota and antimicrobial resistance, highlighting the implications of microbiome diversity in health and disease. Moreover, strategies to mitigate antibiotic resistance, including stewardship programs, alternatives to traditional antibiotics, probiotics, microbiota restoration techniques, and nanotechnology-based therapeutic interventions, are critically presented, setting an updated framework of current management options. Therefore, through a better understanding of respiratory microbiome roles in antibiotic resistance, alongside emerging therapeutic strategies, this paper aims to shed light on how the global health challenges posed by multi-drug-resistant pathogens can be addressed. Full article

Background: Acute lung injury (ALI) is a major cause of death in patients with various viral pneumonias. Our team previously identified four volatile compounds from aromatic Chinese medicines. Based on molecular compatibility theory, we defined their combination as aromatic molecular compatibility (AC), though its therapeutic effects and underlying mechanisms remain unclear. Methods: This study used influenza A virus (IAV) A/PR/8/34 to construct cell and mouse models of ALI to explore AC’s protective effects against viral infection. The therapeutic effect of AC was verified by evaluating the antiviral efficacy in the mouse models, including improvements in their lung and colon inflammation, oxidative stress, and the suppression of the NLRP3 inflammasome. In addition, 16S rDNA and lipid metabolomics were used to analyze the potential therapeutic mechanisms of AC. Results: Our in vitro and in vivo studies demonstrated that AC increased the survival of the IAV-infected cells and mice, inhibited influenza virus replication and the expression of proinflammatory factors in the lung tissues, and ameliorated barrier damage in the colonic tissues. In addition, AC inhibited the expression of ROS and the NLRP3 inflammasome and improved the inflammatory cell infiltration into the lung tissues. Finally, AC effectively regulated intestinal flora disorders and lipid metabolism in the model mice, significantly reduced cholesterol and triglyceride expression, and thus reduced the abnormal accumulation of lipid droplets (LDs) after IAV infection. Conclusions: In this study, we demonstrated that AC could treat IAV-induced ALIs through multiple pathways, including antiviral and anti-inflammatory pathways and modulation of the intestinal flora and the accumulation of LDs. 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

An estimated 10% of COVID-19 survivors have been reported to suffer from complaints after at least three months. The intestinal microbiome has been shown to impact long COVID through the gut–lung axis and impact the severity. We aimed to investigate the relationship between the gut microbiome and clinical characteristics, exploring microbiome heterogeneity through clustering. Seventy-nine patients with long COVID evaluated at 3 to 6 months after infection were sampled for fecal metagenome analysis. Patients were divided into two distinct hierarchical clusters, based solely on the microbiome composition. Compared to cluster 1 (n = 67), patients in cluster 2 (n = 12) showed a significantly reduced lung function (FEV₁, FVC, and DLCO) and during acute COVID-19 showed a longer duration of hospital admissions (48 compared to 7 days) and higher rates of ICU admissions (92% compared to 22%). Additionally, the microbiome composition showed a reduced alpha diversity and lower proportion of butyrate-producing bacteria in cluster 2 together with higher abundances of Ruminococcus gnavus, Escherichia coli, Veillonella spp. and Streptococcus spp. and reduced abundances of Faecalibacterium prausnitzii and Eubacteria spp. Further research could explore the effect of pre- and pro-biotic supplementation and its impact on lung function and societal participation in long COVID. Full article

Lung health is dependent on a complex picture of the lung microbiota composed of bacteriobiota, mycobiota, and virome. The studies have demonstrated that the lung microbiota has a crucial role in host protection by regulating innate and adaptive lung immunity. Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease featuring changed microbiota composition and diversity, known as a dysbiosis. The lung dysbiosis increases with the progress of COPD and during exacerbation. Two models of dysbiosis have been proposed: dysbiosis and inflammation cycles and the disturbance of bacterial interactome. Still, it is unknown if the driving factor of the pathogenesis of COPD belongs to the host or microbiota. Recently, host–microbiota and microbe–microbe interactions have been highlighted in COPD, but the mechanisms behind these interactions need further exploration. The function of the gut–lung axis is crucial for the maintenance of lung health and is affected in COPD. The application of probiotics has resulted in host–beneficial effects, and it is likely that future progress in this field will aid in the therapy of COPD. In this review, the composition of the lung microbiota, molecular mechanisms, and clinical aspects relating to host and microbiota in health and COPD are comprehensively provided. Full article

Inflammation can positively and negatively affect tumorigenesis based on the duration, scope, and sequence of related events through the regulation of signaling pathways. A transcriptomic analysis of five pulmonary arterial hypertension, twelve Crohn’s disease, and twelve ulcerative colitis high throughput sequencing datasets using R language specialized libraries and gene enrichment analyses identified a regulatory network in each inflammatory disease. IRF9 and LINC01089 in pulmonary arterial hypertension are related to the regulation of signaling pathways like MAPK, NOTCH, human papillomavirus, and hepatitis c infection. ZNF91 and TP53TG1 in Crohn’s disease are related to the regulation of PPAR, MAPK, and metabolic signaling pathways. ZNF91, VDR, DLEU1, SATB2-AS1, and TP53TG1 in ulcerative colitis are related to the regulation of PPAR, AMPK, and metabolic signaling pathways. The activation of the transcriptomic network and signaling pathways might be related to the interaction of the characteristic microbiota of the inflammatory disease, with the lung and gut cell receptors present in membrane rafts and complexes. The transcriptomic analysis highlights the impact of several coding and non-coding RNAs, suggesting their relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during lung and gut cell adaptation to inflammatory phenotypes. Full article

Orally administered immunomodulatory lactobacilli can stimulate respiratory immunity and enhance the resistance to primary infections with bacterial and viral pathogens. However, the potential beneficial effects of immunomodulatory lactobacilli against respiratory superinfection have not been evaluated. In this work, we showed that the feeding of infant mice with Lacticaseibacillus rhamnosus CRL1505 or Lactiplantibacillus plantarum MPL16 strains can reduce susceptibility to the secondary pneumococcal infection produced after the activation of TLR3 in the respiratory tract or after infection with RVS. The treatment of mice with CRL1505 or MPL16 strains by the oral route improved the production of interferons in the respiratory tract, differentially modulated the balance of pro- and anti-inflammatory cytokines, reduced bacterial replication, and diminished lung damage. Additionally, we demonstrated that orally administered lactobacilli confer longstanding protection against secondary Streptococcus pneumoniae infection and that this effect would be mediated by the stimulation of trained alveolar macrophages. This work contributes to revealing the mechanisms involved in the modulation of the gut–lung axis by beneficial microbes by demonstrating that specific lactobacilli strains, through the stimulation of the common mucosal immune system, would be able to support the development of trained alveolar macrophages that would confer longstanding protection against secondary bacterial challenges produced after a primary inflammatory event in the respiratory mucosa. Full article

Background: Susceptibility to and severity of pulmonary infections increase with ethanol consumption. We have previously shown that ethanol-induced changes in the gut microbiome disrupt gut homeostasis, allowing for the translocation of proinflammatory mediators into the circulation and eliciting an immune response in the lung. Additionally, targeting the gut with butyrate supplementation not only rescues ethanol-induced disruptions to gut health but also reverses aspects of immune dysregulation in the lungs. Here, we assessed the impact of this connection on a subsequent infectious challenge. Methods: To assess if ethanol-induced alterations to the gut microbiome could also impact the host response to a pulmonary infectious challenge, we employed a chronic-binge ethanol-feeding mouse model followed by a nasal instillation of Pseudomonas aeruginosa. Results: In addition to altering gut microbiome composition and metabolism, ethanol consumption also disrupted the local immune response as demonstrated by suppressed cecal SIgA levels, a decreased presence of CD3⁺CD8a⁺ cytotoxic T cells in the proximal colon mucosa, and depleted CD3⁺CD8a⁺ T cells and CD11c⁺CD8a⁺ dendritic cells in the mesenteric lymph nodes. Circulatory Ly6G⁺CD11b⁺ neutrophils increased, indicating a systemic change in immune-cell presence with ethanol exposure. Ethanol exposure increased CD11c⁺CD64⁺ macrophages and Ly6G⁺CD11b⁺ neutrophils in the lungs, with neutrophil populations being further exacerbated during a bacterial challenge with Pseudomonas aeruginosa. Lipocalin 2, a marker of oxidative stress, was also elevated with ethanol consumption, though not with infection. Conclusions: These data suggest that ethanol-induced changes in the gut microbiome and immune environment are linked to dysfunctional immune responses in the intestine, blood, and the lungs, compromising the pulmonary immune response during an infectious challenge in mice. Full article

Lung cancer is the leading cause of cancer-related fatalities globally, related to inflammatory and gut microbiota imbalance. Brassica rapa L. polysaccharide (BP) is a functional compound, which is utilized by the gut microbiota to regulate immunity and metabolism. However, the effect of BP on lung cancer and whether it affects the “gut–lung” axis remains unclear. This study explored the intervention of BP in Lewis lung cancer (LLC) mice and its effect on the gut microbiota. The results revealed that BP reduced tumor weight and downregulated the expression of Ki67 protein. Additionally, BP reduced the content of inflammatory factors and growth factors, promoting tumor cell apoptosis and inhibiting the growth of LLC. The intervention of BP suppressed intestinal inflammation, preserved intestinal barrier integrity, and augmented the level of beneficial microbiota, such as Blautia and Bifidobacterium. Furthermore, BP significantly increased the production of short-chain fatty acids (SCFAs), particularly butyrate and propionate. A correlation analysis showed significant correlations among the gut microbiota, SCFAs, inflammatory factors, and tight junction proteins. A functional analysis indicated that BP promoted amino acid metabolism and fatty acid metabolism. These findings suggested that BP had the potential to act as prebiotics to prevent disease and improve lung cancer progression by regulating the gut microbiota. Full article