Gut Pathogens最新文献

Background: The widespread adoption of non-caged production systems contributes to the pathogenesis of coinfections with gastrointestinal nematodes and Histomonas meleagridis, triggering local and systemic immune and metabolic responses in chickens. This study investigated transcriptomic adaptation of tissues two weeks after experimental coinfections with Ascaridia galli, Heterakis gallinarum, and H. meleagridis in Lohmann Brown (LB), Lohmann Dual (LD), and Ross-308 (R) male chickens, which differ in growth rates (R > LD > LB).

Results: RNA sequencing of the jejunum, caecum, and liver tissues revealed tissue-specific, strain-dependent transcriptional responses. Coinfection was confirmed during necropsy, and Ascaris-specific antibodies as well as alpha-1-acid glycoprotein were significantly higher in infected birds (p < 0.01). The caecum exhibited the highest unique differentially expressed genes, DEGs (n = 4,094), corresponding to significant activation of complex immune pathways and inhibition of metabolic pathways (p < 0.01). Jejunum DEGs (n = 760) primarily related to muscle contraction, collagen metabolism notably in LB and LD strains. The liver displayed fewer unique DEGs (n = 266) but prominently activated immune responses, especially in R chickens.

Conclusion: In general, slower-performing strains effectively initiated responses favouring worm expulsion and tissue repair in the jejunum, whereas high-performing strains predominantly showed inflammatory responses in the caecum and liver. These findings highlight tissue-specific adaptations underlying strain-dependent tolerance to coinfections with mixed parasites.

Antibiotic use is known to contribute to the development of osteoporosis, although the exact mechanisms remain poorly understood. Metronidazole (MET), a commonly prescribed antibiotic for treating anaerobic infections, has been linked to alterations in the gut microbiota (GM), which in turn are associated with various adverse side effects in the host. Recent studies have shown that the GM plays a key role in regulating bone homeostasis, though the underlying mechanisms remain under investigation. In this study, we demonstrate for the first time that MET promotes inflammatory osteoporosis through gut dysbiosis, with Klebsiella variicola (K. variicola) identified as a major pathogen influencing bone metabolism. The pro-inflammatory extracellular vesicles (EVs) secreted by K. variicola induce enhanced inflammatory responses and osteoclastic differentiation in both bone macrophages and bone tissue. Notably, the use of antibiotics that target K. variicola effectively mitigates MET-induced bone loss in vivo. This study expands our understanding of the mechanisms underlying antibiotic-induced bone loss and underscores the significant role of the pathogenic bacterium K. variicola in the development of osteoporosis, providing new avenues for future research on the microbiota-gut-bone axis in bone-related diseases.

Background: Individuals with compromised immune systems, such as organ transplant recipients who are on immunosuppressive therapy to prevent graft rejection, are at an increased risk of acquiring, disseminating, or experiencing recurrence parasitic infections.

Methods: This study aimed to identify the types and prevalence of parasitic diseases among transplant patients at a comprehensive transplant center in Fars Province, southern Iran. The subjects of the study were 150 organ transplant recipients (kidney, liver, intestine, simultaneous pancreas and kidney [SPK]) who were at least two months post-transplantation. Stool samples were collected from each participant, and demographics along with clinical features were recorded. The stool samples underwent parasitological examination, including direct examination, zinc sulfate flotation, formalin-ethyl acetate sedimentation, trichrome, and acid-fast staining to detect protozoan and helminthic infections. Samples positive for Blastocystis sp., as well as all diarrheal samples suspected of having microsporidia or intestinal coccidia, were further investigated using molecular methods. Sequencing was performed on the PCR products obtained from 10 Blastocystis samples. The resulting sequences were submitted to the Blastocystis 18 S database for GenBank sequence queries.

Results: The mean age of the participants was 46.24 (± 15.13), ranging from 18 to 85 years. Among the 150 subjects, 96 (64%) were male and 54 (36%) were female. The majority had undergone kidney transplantation (52.66%), followed by liver transplantation (46%). The participants resided in various provinces of Iran, with the majority (61.33%) living in Fars province. Overall, 63 (42%) individuals were found to be infected with at least one type of intestinal parasite. Blastocystis sp., the most commonly detected parasite, was detected in 58 (38.66%) cases, Entamoeba coli and Iodamoeba butchlii were each detected in 2 (1.33%) cases, while Enterocytozoon bieneusi was identified in 1 (0.66%) case. No helminth infections were detected in any of the subjects. Sequencing of Blastocystis sp. revealed subtype 3 (ST3).

Conclusion: The study highlights a high prevalence of intestinal protozoa, particularly Blastocystis sp., among transplant recipients in southern Iran. The detection of E. bieneusi underscores the critical need for greater awareness of these parasitic agents, especially in cases presenting with diarrhea.

Non-tuberculous mycobacteria (NTM) are emerging pathogens of global concern, particularly in regions with declining tuberculosis rates. This review synthesizes current evidence on the epidemiology, immune pathogenesis, and microbiome interactions underlying NTM infections. The rising incidence of NTM is driven by environmental factors, immunocompromised populations, and advanced diagnostics. Clinically, NTM manifests as pulmonary, lymphatic, skin/soft tissue, or disseminated disease, with Mycobacterium avium complex (MAC) and M. abscessus being predominant pathogens. Host immunity, particularly Th1 responses mediated by IL-12/IFN-γ and TLR2 signaling, is critical for controlling NTM, while dysregulated immunity (e.g., elevated Th2 cytokines, PD-1/IL-10 pathways) exacerbates susceptibility. Emerging research highlights the gut-lung axis as a pivotal mediator of disease, where microbiome dysbiosis-marked by reduced Prevotella and Bifidobacterium-impairs systemic immunity and promotes NTM progression. Short-chain fatty acids (SCFAs) and microbial metabolites like inosine modulate macrophage and T-cell responses, offering therapeutic potential. Studies reveal distinct airway microbiome signatures in NTM patients, characterized by enriched Streptococcus and Prevotella, and reduced diversity linked to worse outcomes. Despite advances, treatment remains challenging due to biofilm formation, antibiotic resistance, and relapse rates. This review underscores the need for microbiome-targeted therapies, personalized medicine, and longitudinal studies to unravel causal relationships between microbial ecology and NTM pathogenesis.

Background: Helicobacter pylori (H. pylori) is a lifelong infection, often acquired in childhood and persisting throughout life, that can lead to serious gastric diseases, including gastric cancer in adults. While asymptomatic in most children, it may cause extraintestinal manifestations affecting growth, necessitating distinct pediatric management strategies-particularly in countries with a high risk of gastric cancer. Accurate diagnosis is critical in high-risk populations. The stool antigen test is a reliable, non-invasive method for young children. Despite Bhutan's high H. pylori burden, diagnostic tools remain scarce. This study aimed to determine the prevalence and risk factors of H. pylori infection in Bhutanese children and validate a new in-house immunochromatography test (the A-ICT) kits.

Methods: A cross-sectional study was conducted in 2023 among children under 64 months of age at three immunization clinics in Thimphu. H. pylori antigen in stool was detected using an ICT kit. After obtaining informed consent, parents completed questionnaires. Data were analyzed using STATA version 14.2 and R version 4.4.1.

Results: A total of 226 children (mean age 33.28 months) participated in the study. The A-ICT kit showed high concordance with the commercial kit (Kappa 0.84 [95% CI: 0.78-0.89]) and excellent sensitivity (0.96) and specificity (0.95). The prevalence of H. pylori was 19.54% (95% CI:14.95-24.83). Risk factors included increasing age, having two or more siblings, and fathers who were farmers/wagers, and who worked in government/private sector. Children who were fed with or who ate using a spoon had a significantly lower risk of H. pylori infection than those who were fed or ate with fingers (p < 0.05).

Conclusions: The A-ICT kit demonstrated remarkable sensitivity and specificity. Improvements in hygiene and sanitation related to child feeding practices are essential. Awareness programs should target large families and individuals employed in the formal sector, including both household and workplace settings. The validation of the A-ICT is a significant step toward a gastric cancer prevention program that facilitates early diagnosis and H. pylori eradication. The test kit is highly recommended for H. pylori screening and the confirmation of eradication post-treatment given its accuracy, rapidity, and simplicity in execution.

Traditionally regarded as a vestigial organ, the appendix is now being reevaluated for its significant function in health and nutrition of humans. Serving as a "safe house" for beneficial, desired gut bacteria, the appendix is protected by resilient biofilms that create a secure environment. This makes the appendix a"basin" for gut microbiota (GM), replenishing the microbial population following disruptions from infections, antibiotic use, or inflammatory bowel disease (IBD). Beyond simply hosting bacteria, the appendix has an active role in functions of the immune system. Disruption of the Appendix Microbiome (AM), such as through appendectomy, was found to result in lowered diversity of gut microorganisms and an increased risk of various diseases. The potential therapeutic applications of the AM are a particularly promising area of research. The appendix's unique microbial environment and its impact on immunity open new avenues for treatments. These include modulating GM to improve cancer treatment outcomes, mitigating IBD, regulating metabolic pathways in obesity and diabetes, influencing neurotransmitter production in neurological disorders, and addressing cardiovascular and autoimmune diseases. This review highlights the appendix's transformation from a misunderstood organ to a critical component of gut health and immunity. It explores the function of the human appendix as a resilient reservoir for desired microorganisms, and its role in disease progression. Furthermore, it examines the potential therapeutic applications of AM, presenting exciting opportunities for future research and treatment innovations.

The global rise in antibiotic resistance has posed significant challenges to the effective management of Helicobacter pylori (H. pylori), a gastric pathogen linked to chronic gastritis, peptic ulcers, and gastric cancer. Conventional antibiotic therapies, while effective, face significant challenges, such as increasing antibiotic resistance, high recurrence rates, and adverse effects such as gut microflora dysbiosis. These limitations have driven the exploration of alternative antibiotic-free therapies, including the use of plant-based compounds, probiotics, nanoparticles, phage therapy, antimicrobial peptides, and H. pylori vaccines. Among these, urease-targeted therapy has shown particular promise. Urease enables the survival and colonization of H. pylori by neutralizing stomach acidity. Targeting this urease without disrupting beneficial gut microflora offers a selective mechanism to impair H. pylori, due to the absence of this enzyme in most of the human gut microbiome. In this review, we highlight advancements and limitations in the field of antibiotic-free therapies, with a particular focus on anti-urease strategies. We explore the structural and functional characteristics of urease, its role in H. pylori pathogenesis, and its potential as a therapeutic target. For the first time, we provide a comprehensive analysis of natural, semisynthetic, and synthetic anti-urease compounds, emphasizing their mechanisms of action, efficacy, and safety profiles. Advances in silico, in vitro, and in vivo studies have identified several promising anti-urease compounds with high specificity and minimal toxicity. By focusing on urease inhibition as a targeted strategy, this review underscores its potential to overcome antibiotic resistance while minimizing gut dysbiosis and improving the outcomes of H. pylori infection treatment.

Background: Klebsiella pneumoniae producing extended-spectrum β-lactamase (ESBL) colonizing and transmitting in the intestine, especially in children, have significant public health implications. Investigating antibiotic resistance, antibiotic resistance genes (ARGs), virulence factor genes (VFGs), and genetic relationships may help us to explore the characteristics and differences of ESBL-positive K. pneumoniae in children with and without diarrhea.

Methods: After selecting and pairing, 26 pairs of 52 ESBL-positive K. pneumoniae strains were isolated from 323 children with diarrhea and 393 children without diarrhea. Antimicrobial susceptibility test and whole genome sequencing were performed to explore antibiotic resistance, ARGs, and VFGs. The genetic relationship was explored by conducting a maximum likelihood phylogenetic tree and investigating plasmid and sequence type (ST).

Results: All strains showed resistance to cephalosporins, with ESBL-producing genes widely carried (98.1%). Carbapenem-resistant K. pneumoniae (CRKP) were found in both groups. Hypervirulent K. pneumoniae (hvKP) were isolated from children with diarrhea carrying iucA on plasmid. The emergence of ST5670 CRKP and ST2108 hvKP highlighted the necessity for close monitoring of community-acquired K. pneumoniae.

Conclusions: Severe drug resistance was found among ESBL-positive K. pneumoniae strains isolated from children with and without diarrhea. Attention must be paid to ESBL-positive K. pneumoniae colonized in the intestine of children, and pathogen and ARG monitoring in children should be strengthened, even in healthy people.

The identification of Helicobacter pylori (H. pylori) infection as the primary etiology of gastroduodenal diseases represents a significant advancement in the field of gastroenterology. The management of these diseases has undergone a substantial transformation, and antibiotic treatment is now universally applicable. H. pylori has been the subject of numerous investigations to determine the prevalence of antibiotic resistance. However, many of these studies are limited, particularly regarding the number and representativeness of the strains assessed. Genetic and physiological modifications, such as gene mutations, efflux pump alterations, biofilm formation, and coccoid formation, contribute to the observed resistance. Our review focuses on the emergence of antibiotic-resistant strains, particularly emphasizing the various modifications of H. pylori that confer this resistance. In conclusion, we elucidate the challenges, potential solutions, and prospects in this field, providing researchers with the knowledge necessary to overcome the resistance exhibited by H. pylori.