Gut Pathogens最新文献

Emerging evidence suggests the link between pulmonary tuberculosis (PTB) and gut microbiota dysbiosis. This is the first study from the southern Indian population that characterized the gut microbiota of PTB patients using 16 S amplicon sequencing. The analysis revealed a significant reduction in gut microbial diversity among PTB patients, with particularly lower alpha diversity (Chao1 index, p ≤ 0.0001) than healthy controls (HC). This was further depleted during antitubercular therapy (ATT). Beta diversity indicated distinct clustering in all the groups (p < 0.05). Subgroup analyses showed that supplementation of probiotics with ATT improved microbial richness and diversity. However, broader shifts in composition were not observed. At the genus level, specific taxa were upregulated or downregulated in PTB patients compared to HC. Functional analysis showed a depletion in biosynthesis pathways in PTB patients. Short-term probiotic supplementation had a partial effect on microbial recovery but did not fully restore gut microbial diversity. These findings highlight persistent dysbiosis in PTB patients, even after ATT. Large-scale studies are needed to evaluate the role of microbiome-targeted therapies to address this dysbiosis.

Aim: Blastocystis spp. is a common intestinal protozoan with controversial pathogenicity. It is frequently associated with gastrointestinal (GIT) disturbances and is particularly prevalent among immunocompromised individuals. This study aimed to assess the prevalence of Blastocystis spp. infection and its association with immunological and hematological parameters among chronic leukemic patients.

Methods: Stool and blood samples were collected from 100 chronic leukemic patients. Microscopic examination and a coproantigen assay were performed for the detection of Blastocystis spp., along with assessment of anti-Blastocystis fecal IgA and serum IgG antibodies. CD4 T cells and the serum level of IL-8 were also measured.

Results: The overall Blastocystis spp. infection rate was 60%, determined through combined microscopy and/or coproantigen detection. Among infected patients, anti-Blastocystis IgA was positive in only three patients and IgG in 18 patients, with no statistically significant association between Blastocystis spp. infection and detection of antibodies. Infection was significantly associated with elevated IL-8 levels and WBC count. There was no statistically significant association between the presence of gastrointestinal symptoms and the levels of anti-Blastocystis IgG or IgA, IL-8, or CD4 count in Blastocystis spp.-infected patients.

Conclusion: Our study reveals a high prevalence of Blastocystis spp. infection among chronic leukemic patients and identifies a significant association between infection and elevated IL-8 levels.

Background: Fusobacterium animalis (Fa) was identified as the most enriched Fusobacterium species in colorectal cancer (CRC). Recently, a group of Fa core genes were found to be highly expressed intratumorally and to favor intracellular survival. We hypothesized that, because they promote bacterial fitness in the intracellular niche, these genes might be targets of positive selection, a process that often underlies adaptation to variable environments.

Results: We performed an evolutionary analysis to identify selective events that occurred over different time frames, namely during the divergence of the Fusobacterium species and in the more recent separation of the Fa lineage from F. paranimalis. Results indicated that the coding sequences of these genes have been targeted by intense purifying selection, possibly as the result of their often-essential functions. However, localized signatures of positive selection were also detectable. During the divergence of Fusobacterium species, the major target of positive selection was represented by elongation factor-Tu, a finding that may be related to its moonlighting functions in adhesion and biofilm development. Additional targets were RpoC and the septum-determining protein MinD. We suggest that variations in the latter contribute to the observed differences in cell length and width between F. watanabei and Fa. We also searched for and detected beneficial changes that occurred specifically in the Fa lineage, suggesting that such variants promote intracellular growth or adaptation to the tumor microenvironment. The strongest target of selection was DnaK, which was shown to promote malignant transformation in other bacterial systems. Analysis of the selected sites in DnaK indicated that most of them are located in the C-terminal unstructured region and that they determine the appearance of eukaryotic linear motifs (ELMs). Specifically, one ELM is a casein kinase 2 phosphorylation site, whereas two additional ELMs are involved in SUMOylation and USP7-mediated deubiquitination. USP is a central modulator of the p53-MDM2 pathway and we propose that SUMOylation facilitates the nuclear import of Fa DnaK where USP7 promotes its stability.

Conclusion: We identified specific proteins and amino acid changes that are expected to underlie phenotypic diversity in Fusobacteria. These data are relevant to inform future analyses of Fa oncogenic potential.

The development of gastric cancer is significantly influenced by the intestinal microbiota, with H. pylori serving as a major risk factor. Through genotoxic effects, persistent inflammation, and metabolic changes, other microbes also play a role. It has been demonstrated that cancer patients and healthy people have different microbiome compositions. Cancer can be inhibited or promoted by the gut microbiota and its metabolites. The relationship between intestinal flora, bacterial extracellular vesicles, and the tumor microenvironment directly affects tumor progression and efficacy of anti-tumor medications, indicating the importance of the tumor microenvironment in tumor survival. Gastrointestinal malignancies may be brought on by the gut microbiome's dysregulation of non-coding RNA expression. Non-coding RNAs are intriguing avenues for future therapeutic and diagnostic research. The tumor microenvironment is altered by bacterial extracellular vesicles, which may have an effect on immunosuppression, treatment resistance, metastasis, and cancer progression. Further research is required to completely understand the involvement of non-coding RNAs in GI cancers. By modifying drug metabolism and absorption, which have a substantial impact on healing efficacy and serious impact profiles, the dynamic changes in gut microbiota also have a considerable impact on the results of anti-cancer treatment. Improved treatment approaches may arise from a better understanding of the role of the microbiome in gastric malignancies.

The gut microbiome plays a critical role in human health through its influence on numerous physiological functions such as metabolism and immunity, with disruptions in microbial communities increasingly linked to metabolic disorders. In a large-scale cohort study in Japan, we investigated the association between gut microbiome profiles and metabolic health. Using 16S rRNA gene sequencing, four-enterotype clustering revealed that the Bacteroides 2 (B2) enterotype was associated with lower alpha-diversity and increased risk of metabolic diseases, particularly obesity (OR = 1.51) and hypertension (OR = 1.49). Refined seven-enterotype clustering further stratified the Ruminococcus, Prevotella, and Bacteroides enterotypes into distinct subtypes, uncovering a novel high-risk Prevotella 2 (P2) enterotype associated with nearly two-fold increased risk of obesity and diabetes mellitus. The B2 and P2 enterotypes were characterized by reduced abundance of beneficial short-chain fatty acid (SCFA) producers (Faecalibacterium, Anaerostipes) and enrichment of opportunistic pathogens (Fusobacterium and Veillonella for B2, Megamonas and Megasphaera for P2). Microbial metabolic influence network analysis revealed enterotype-specific interaction patterns, with R1, R2, and P1 enterotypes demonstrating cooperative production of SCFAs and other metabolites, while B enterotypes displayed synergy in the production of a range of sugar compounds. These findings underscore the utility of refined enterotype clustering as a powerful tool to reveal previously unrecognized gut microbial patterns linked to metabolic risk. By identifying B2 and the newly characterized P2 enterotypes as high-risk microbial profiles, this study opens new avenues for microbiome-based stratification and early intervention in metabolic disease management.

Background: liver fibrosis is associated with dysregulated iron homeostasis regulated by the hepcidin-ferroportin axis, and dysbiotic gut microbiota. This study aimed to investigate the preventive and ameliorative effects of live and cell-free supernatant (CFS) forms of Akkermansia muciniphila and Faecalibacterium prausnitzii, as important gut microbiota members, on liver fibrosis by targeting the hepcidin-ferroportin axis in both in vitro and in vivo models.

Methods: At the in vitro level, the effects of A. muciniphila and F. prausnitzii on the expression of collagen type I alpha 1 (COL1A1) and ferroportin (SLC40A1) transcripts in hepatic stellate cells (HSCs) were evaluated in transforming growth factor beta (TGFβ)-activated LX-2 cells, a human hepatic stellate cell line. In vivo, male C57BL/6 mice were intraperitoneally (IP) injected with 10% carbon tetrachloride (CCl₄) twice weekly for 6 weeks to establish the liver fibrosis model. Administration of live and CFS forms of A. muciniphila and F. prausnitzii was initiated 10 days before CCl₄ injection and continued until the end of the experiment. Liver injury and fibrosis were assessed using serum markers, hematoxylin and eosin (H&E), and Masson's trichrome staining. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) were used to evaluate the effects of the interventions on gene expression related to the hepcidin-ferroportin axis in liver, colon and brain samples. Additionally, qPCR was used to determine alterations in the relative abundance of key gut microbiota members in fecal samples.

Results: Both A. muciniphila and F. prausnitzii, as well as their CFS, significantly downregulated COL1A1 expression in TGFβ-activated LX-2 cells, accompanied by reduced alpha-smooth muscle actin (α-SMA) protein expression in liver tissue. In vivo, intervention with F. prausnitzii, particularly its CFS, led to a greater induction of hepatic hepcidin and ferroportin expression compared to A. muciniphila and its CFS. Serum liver injury markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH)) and iron levels were markedly improved following treatment with live F. prausnitzii and its CFS. Additionally, F. prausnitzii CFS significantly enhanced hepcidin gene expression in brain tissue, suggesting broader systemic benefits.

Conclusion: We demonstrated that F. prausnitzii and its CFS had greater beneficial potential than A. muciniphila and its CFS in the prevention and amelioration of liver fibrosis, likely through modulation of the hepcidin-ferroportin axis. These findings may support the development of next-generation probiotics and postbiotics for liver injury, which warrants further investigation.

Background: Tumor tissues have been shown to host a diverse array of bacteria, suggesting a link between the intratumoral microbiota and the development and progression of cancer. The aim of this explorative study was to perform microbiome analysis in liver tumor and to evaluate its relationship with cancer stage and survival outcome.

Results: We conducted an exploratory study on a cohort of 20 hepatocellular cancer patients from the SORAMIC trial. Patients were divided into curative and palliative groups according to treatment type (local ablation, alone or combined with systemic therapy). The V1-V2 regions of 16 S rRNA were sequenced starting from archival tissues. Amplicon Sequence Variants (ASVs) were taxonomically assigned to the upper (UGI) or lower (LGI) gastrointestinal tract. Bacteria were identified in both tumoral and non-tumoral tissues, showing higher diversity and correlation between diversity and shorter survival in the palliative group (S. aureus p < 0.05; B. parvula p < 0.01; A. chinensis p < 0.01). Both therapy groups were enriched with the genus Bacilli, including Streptococcus spp., Gemella haemolysans and Helicobacter pylori, commonly found in UGI. The results suggested that among palliative patients and those with shorter survival, G. haemolysans was more prevalent, while H. pylori was more often found in curative patients with longer survival. However none of the results were significantly different (p > 0.05). A higher microbiome biodiversity was associated with an increased number of lesions (Hoylesella, Agathobacter, Sphingobium, Cardiobacterium, Photobacterium and Serratia, all with p < 0.01).

Conclusions: The presence of bacteria, predominantly from communities of the UGI, suggests their translocation into liver tissue due to impaired barrier function of the upper gut or the ascending pathway along the biliary duct system. The intratumoral prevalence of bacteria with proinflammatory and oncogenic potential suggests their potential role in HCC pathomechanisms.

Background: Reptiles are recognized as reservoirs of Salmonella bacteria, and the expansion of the global pet reptile trade has led to reptile-associated salmonellosis emerging as a significant public health concern. To characterize the risk posed by reptiles as a source of Salmonella transmission to humans, we conducted the first comprehensive meta-analysis to estimate the worldwide prevalence of Salmonella in both wild and captive reptiles and identify the primary factors influencing this prevalence.

Results: We systematically reviewed publications reporting the prevalence of Salmonella spp. intestinal isolation in reptiles, published between 1986 and 2023, across the PubMed, Scopus and Web of Science databases. The 179 studies included examined a total of 23,411 reptiles from 56 countries across all continents, with 49.9% being free-ranging animals and 48.4% living in captivity, mainly from zoos, pet shops, or households. The overall pooled prevalence of Salmonella spp. in reptiles was estimated at 30.4% (95% confidence interval, CI: 27.4-33.6%). Notably, significant variations in Salmonella spp. colonization rates were observed across different reptile taxa, with snakes exhibiting the highest prevalence at 63.1% (95%CI: 57.4-68.4%), followed by lizards at 33.6% (95%CI: 28.6-39.0%), and turtles and crocodiles with similar rates of 11.2% (95%CI: 8.8-14.2%) and 10.5% (95%CI: 5.7-18.6%), respectively. Furthermore, significant differences in Salmonella spp. prevalence were observed across different reptile families within each taxon. The data suggest that captivity is a contributing factor to Salmonella spp. colonization, as captive reptiles showed significantly higher prevalence rates (37.8%, 95%CI: 34.3-41.4%) compared to their wild counterparts (14.8%, 95%CI: 11.0-19.6%). Additionally, we found that the inclusion of pre-enrichment and selective enrichment steps in culture broths significantly improved the sensitivity of both culture-based and PCR-based Salmonella detection methods. Importantly, the study revealed that reptiles primarily carried Salmonella enterica subspecies enterica, responsible for most human salmonellosis cases. Of particular concern, several human-pathogenic Salmonella serovars of public health relevance, such as Enteritidis, Typhimurium and Newport, were identified among the 10 most common serovars colonizing reptiles.

Conclusions: Collectively, these findings highlight the substantial health threat posed by reptiles as a source of human Salmonella infection and may inform the development of policies and strategies for prevention and public education to mitigate the risk of reptile-associated salmonellosis.