Gut Pathogens最新文献

Background: Campylobacter infections pose a significant challenge in low- and middle-income countries, contributing to child mortality. Campylobacter is linked to acute gastrointestinal illness and severe long-term consequences, including environmental enteric dysfunction (EED) and stunting. In 2018, our cross-sectional study in Ethiopia detected Campylobacter in 88% of stools from children aged 12-15 months, with an average of 11 species per stool using meta-total RNA sequencing. Building on these findings, we conducted a longitudinal study (December 2020-June 2022) to investigate Campylobacter colonization of infants and identify reservoirs and risk factors in rural eastern Ethiopia.

Results: After a preliminary screening of 15 Campylobacter species using species-specific quantitative PCR, we analyzed four target species in 2045 samples from infants (first month to just one year of life) and biannual samples from mothers, siblings, and livestock (goats, cattle, sheep, and chickens). Candidatus C. infans (41%), C. jejuni (26%), and C. upsaliensis (13%) were identified as the predominant in the infant gut. Colonization of C. infans and C.jejuni increased (C. infans: 0.85%, C. jejuni-0.98% increase/ day in the odds of colonization) and abundance (P = 0.027, 0.024) with age. Enteric symptoms were strongly associated with C. infans (diarrhea: OR = 2.02 [95%CI: 35%,100%]; fever: OR = 1.62 [95%CI: 14%, 83%]) and C. jejuni (diarrhea: OR = 2.29 [95%CI: 46%,100%], fever: OR = 2.53 [95%CI: 56%,100%]). Based on linear mixed models, we found elevated cumulative loads of C. infans load in infants (especially females OR = 1.5 [95%CI: 10%, 67%]), consuming raw milk (OR = 2.3 [95%CI: 24%,100%]) or those exposed to areas contaminated with animal droppings (OR = 1.6 [95%CI: 7%,93%]), while C. jejuni cumulative loads were higher in infants ingesting soil or animal feces (OR = 2.2 [95%CI: 23%,100%]). C. infans was also prevalent in siblings (56%) and mothers (45%), whereas C. jejuni was common in chickens (38%) and small ruminants (goats 27%, sheep 21%).

Conclusions: Campylobacter was highly prevalent in rural Ethiopian infants. C. infans was primarily associated with human hosts, and C. jejuni was mainly linked to zoonotic sources. Our findings emphasize the need for targeted interventions addressing environmental, dietary, and behavioral factors to reduce Campylobacter transmission in resource-limited settings.

Background: The immune recovery process in Acquired Immune Deficiency Syndrome (AIDS) is complex and influenced by numerous factors. Gut microbiota and their metabolites play a critical role in maintaining immune homeostasis. Additionally, the presence of Helicobacter pylori in the stomach can affect immune reconstitution in human immunodeficiency virus (HIV)/AIDS patients, either directly or through interactions with the gut microbiota.

Methods: This review adopts a comprehensive literature review approach. It systematically examines a wide range of relevant studies focusing on the interplay between HIV/AIDS immune reconstitution, gut microbiota, and H. pylori.

Results: The review reveals intricate relationships among these components. Gut microbiota and their metabolites are essential for sustaining immune balance. H. pylori influences immune reconstitution in HIV/AIDS patients through various mechanisms, including inducing gut microbiota dysbiosis, altering gastric pH, promoting systemic inflammation, and acting synergistically with HIV. These effects can exacerbate CD4⁺ T cell depletion and may contribute to incomplete immune recovery by disrupting gut microbiota composition.

Conclusion: Understanding these interactions provides a foundation for future research directions. Such insights may offer new perspectives and strategies to address the clinical challenge of immunological non-response in HIV/AIDS patients.

As robust animal models to study the pathophysiology of stunting are absent, we have comparatively characterized the gut microbiota of malnourished/stunted vs. clinically healthy/normal Kenyan toddlers (12-24 months old) and established a gnotobiotic (Gn) pig fecal transplant model to gain understanding of microbial community structure associated with stunting. As expected, the bacterial composition between the two toddler groups was distinct: Actinobacteria was most prevalent in healthy toddlers, whereas Proteobacteria dominated in stunted toddlers. Although the diversity indices showed no significant differences, unique bacterial genera were found in each toddler group: three genera unique to stunted toddlers and ten unique to healthy toddlers, with eight genera shared between the groups. We observed a higher number of enriched bacterial virulence genes in healthy vs. stunted toddlers suggesting that the microbiome plasticity and functional characteristics of the healthy toddlers allow for the pathogen/pathobiont control. In contrast, we noted the presence of more genes associated with antimicrobial-resistance (AMR) bacteria in stunted toddlers, possibly due to early-life antibiotic treatments. Of interest, functional analysis showed that CAZymes associated with carbohydrate biosynthesis, and a few metabolic pathways related to protein/amino acid, carbohydrate and fat catabolism were enriched in stunted toddlers. In contrast carbohydrate degradation CAZymes and numerous anabolic pathways were prevalent in healthy toddlers. These patterns were also evident in the Gn pigs transplanted with stunted/healthy human fecal microbiota (HFM). Overall, our findings suggest that the microbiota transplanted Gn pigs represent a valuable model for studying the infant microbial community structure and the impacts of stunting on the child gut microbiota. Additionally, this is the first study to demonstrate that the healthy vs. stunted microbiota composition and function remained different in the Gn pigs throughout the study. This information and the Gn pig model are vital for developing and testing targeted interventions for malnourished/stunted populations, consequently advancing microbiome-based diagnosis and personalized medicine.

Background: Arcobacter cryaerophilus is considered an emerging foodborne pathogen and is associated primarily with infectious gastrointestinal disease in humans. However, the underlying pathogenic mechanisms remain poorly understood. Therefore, the aim of the present study was to investigate the pathogenic potential of twelve A. cryaerophilus strains using various in vitro assays in two human colonic cell lines, HT-29/B6 and T84.

Results: All strains tested were able to adhere to and invade into both cell lines, with strain-dependent differences in their adhesion and invasion rates. In addition, two strains showed cytotoxic effects on both cell lines. The ability to disrupt the epithelial barrier function of T84 cell monolayers was shown for two strains by measurement of transepithelial electrical resistance. As structural factors correlate with the barrier dysfunction, immunofluorescence staining of the tight junction domain was performed, and revealed an altered distribution of claudin-5 in infected cells.

Conclusions: The results highlight the strain-dependent pathogenic mechanisms of A. cryaerophilus that may contribute to key symptoms such as diarrhoea. These findings also highlight the importance of further research into the pathogen A. cryaerophilus.

Mutations within the hepatitis B virus surface antigen (HBsAg) were found to correlate with progressive liver diseases, including hepatocellular carcinoma (HCC). Mutations in this region can impact viral morphogenesis, virus-host interactions, and immune responses. In this cross-sectional study, we screened for mutations in the pre-S/S regions of HBsAg in sequences retrospectively generated from samples collected in Saudi Arabia. We analyzed 304 full-length HBsAg sequences isolated from samples collected from four clinical groups: inactive (n = 180), active (n = 62), liver cirrhosis (LC) (n = 36), and HCC (n = 26). Three mutations (N103D, Q30K, and I208T) in HBsAg showed significantly higher frequencies in the HCC group compared to other clinical groups. Additionally, the presence of the three mutations combined was significantly associated with HCC in a multivariate analysis. The evolutionary analysis further revealed that these mutation sites are subjected to positive selection within the HCC group. The structural analysis suggested that position 103 within HBsAg pre-S₁ region is prominently accessible and mutations at this site may disrupt interactions with viral/cellular factors or impact recognition by immune responses. Collectively, our findings highlight a significant increase in the frequency of three HBsAg mutations in a cohort of HCC patients in Saudi Arabia and their potential effect.

Systemic lupus erythematosus (SLE) is an autoimmune disorder branded via over-activation of the immune system, resulting in atypical roles of natural and adaptive immune cells and the making of numerous autoantibodies against nuclear components. The causes and pathogenesis of this disease are not completely realized. The gut microbiota plays a significant character in human health and disorder, particularly in autoimmune diseases.Gut microbiome dysbiosis can affect the host immune system as suggested by several recent studies, balance and activity of the gut microbiome, which are influenced by daily diet, might be associated with disease activity in SLE. There are rising signs to support the immunomodulatory abilities of certain probiotics. Numerous investigational and clinical surveys have demonstrated the useful effects of certain probiotic bacteria, mainly strains of Lactobacillus and Bifidobacterium, in patients with SLE. Various species of bacteria were found to be positively or negatively associated with SLE gut microbiomes. A better comprehension of the Studying the gut microbiota will provide a good opportunity to identify microbes involved in tolerance in systemic lupus patients. The purpose of this study is to review the existing literature on probiotics that have the ability to restore tolerance and modulate the levels of inflammatory or anti-inflammatory cytokines that play a role in SLE.

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide, causing a serious threat to global health and social burden. Clostridioides difficile infection (CDI) is one of the most important nosocomial infections and has a higher incidence in cancerous population compared with non-cancerous cases. Different risk factors, including gut microbiota dysbiosis, extensive surgery, chemotherapy, prolonged hospitalization, and antimicrobial therapy, compromise host defenses against CDI and contribute to cancer patients' susceptibility to this infection. The emergence of CDI in patients with CRC creates conditions for therapy escalation and prolonged hospitalization, highlighting the need for correct and effective CDI management in these patients. Here, common risk factors associated with CDI in patients with CRC are discussed. In addition, different available techniques for the prevention, detection, and treatment of CDI with the lowest impact on gut microbiota diversity are summarized. This review aims to improve the understanding of the interplay between CDI and CRC and provide new insights into restoring and maintaining gut microbiota balance during CDI management in patients with CRC.

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.