Intratumoral microbiota can affect the development and progression of many types of cancer, including gastric cancer. A better understanding of the precise mechanisms by which microbiota support gastric cancer could lead to improved therapeutic approaches. In this study, we investigated the effect of intratumoral microbiota on the tumor immune microenvironment during gastric cancer malignant progression. Analysis of human gastric cancer tissues with 16S rRNA amplicon sequencing revealed that Fusobacterium nucleatum was significantly enriched in gastric cancer tissues with lymph node metastasis and correlated with a poor prognosis. F. nucleatum infection spontaneously induced chronic gastritis and promoted gastric mucosa dysplasia in mice. Furthermore, gastric cancer cells infected with F. nucleatum showed accelerated growth in immunocompetent mice compared with immunodeficient mice. Single-cell RNA sequencing uncovered that F. nucleatum recruited tumor-associated neutrophils (TAN) to reshape the tumor immune microenvironment. Mechanistically, F. nucleatum invaded gastric cancer cells and activated IL17/NF-κB/RelB signaling, inducing TAN recruitment. F. nucleatum also stimulated TAN differentiation into the protumoral subtype and subsequent promotion of PD-L1 expression, further facilitating gastric cancer immune evasion while also enhancing the efficacy of anti–PD-L1 antibody therapy. Together, these data uncover mechanisms by which F. nucleatum affects gastric cancer immune evasion and immunotherapy efficacy, providing insights for developing effective treatment strategies. Significance: Intratumoral F. nucleatum activates NF-κB signaling to facilitate gastric cancer immune evasion by promoting tumor-associated neutrophil recruitment that sensitizes tumors to immune checkpoint blockade therapy.

Antibiotic resistance in bacteria has become a major global health problem. One of the main reservoirs of antibiotic resistance genes is the human gut microbiota. To characterise these genes, a metagenomic approach was used. In this study, a comprehensive antibiotic resistome catalog was established using fecal samples from 246 healthy individuals from world’s longevity township in Jiaoling, China. In total, 606 antibiotic resistance genes were detected. Our results indicated that antibiotic resistance genes in the human gut microbiota accumulate and become more complex with age as older groups harbour the highest abundance of these genes. Tetracycline resistance gene type tetQ was the most abundant group of antibiotic resistance genes in gut microbiota, and the main carrier of antibiotic resistance genes was Bacteroides. Antibiotic efflux, inactivation, and target alteration were found to be the dominant antimicrobial resistance mechanisms. This research may help to establish a comprehensive antibiotic resistance catalog that includes extremely long-lived healthy people such as centenarians, and may provide potential recommendations for controlling the use of antibiotics.

Secreted phosphoprotein 1 (SPP1) shows carcinogenic potential in multiple cancers, yet its role in nasopharyngeal carcinoma (NPC) remains elusive. Leveraging transcriptomic data sourced from an NPC cohort at Fujian Cancer Hospital, alongside datasets from the Gene Expression Omnibus cohort and a single-cell RNA sequencing dataset, this investigation explored the role of SPP1 in tumor progression and the tumor microenvironment of NPC. A co-culture system involving tumor cells and macrophages was established to elucidate the relationship between SPP1 and tumor-associated macrophages in NPC. Subsequently, we established an SPP1-driven M2 macrophage signature using a machine-learning-based framework to predict patient prognosis. The results of our analysis indicated that SPP1 is associated with an elevated risk of disease progression and poor prognosis in NPC. Single-cell analysis demonstrated that SPP1 is a pivotal gene in the polarization of M2 macrophages within the tumor microenvironment. In vitro experiments demonstrated that NPC-derived SPP1 has the potential to activate the CD44/JAK2/STAT3 signaling pathway, promoting macrophage recruitment and polarization of the M2 subtype. Furthermore, we established a comprehensive SPP1-related M2 macrophage signature that can predict the prognosis and immune characteristics of patients with NPC. Our findings offer new insights into the role of SPP1 in the tumor microenvironment of NPC, and provide a novel SPP1-driven M2 macrophage signature with the potential to serve as a valuable tool for prognosis prediction and personalized therapy in NPC.

Hypercholesterolemia can cause many diseases, but it can effectively regulated by Lactobacillus. This study aimed to evaluate the cholesterol-lowering mechanism of Enterococcus faecium strain 132 and Lactobacillusparacasei strain 201. These results showed that both the strains decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), liver TC and TG and increased fecal TC, TG and total bile acid (TBA) levels. Additionally, both strains also reduced glutamic-pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST) and levels of tissue inflammation levels to improve the lipid profile, and they reduced fat accumulation partially by alleviating inflammatory responses. Furthermore, both strains regulated the expression of the CYP8B1, CYP7A1, SREBP-1, SCD1 and LDL-R gene to promote cholesterol metabolism and reduce TG accumulation. Interventions with both strains also altered the gut microbiota, and decreasing the abundance of Veillonellaceae, Erysipelotrichaceae and Prevotella. Furthermore, fecal acetic acid and propionic acid were increased by this intervention. Overall, the results suggested that E. faecium strain 132 and L. paracasei strain 201 can alleviate hypercholesterolemia in rats and might be applied as a new type of hypercholesterolemia agent in functional foods.

From December 2012 to February 2013, two outbreaks of acute respiratory disease caused by HAdV-7 were reported in China. We investigated possible transmission links between these two seemingly unrelated outbreaks by integration of epidemiological and whole-genome sequencing (WGS) data. WGS analyses showed that the HAdV-7 isolates from the two outbreaks were genetically indistinguishable; however, a 12 bp deletion in the virus-associated RNA gene distinguished the outbreak isolates from other HAdV-7 isolates. Outbreak HAdV-7 isolates demonstrated increased viral replication compared to non-outbreak associated HAdV-7 isolate. Epidemiological data supported that the first outbreak was caused by introduction of the novel HAdV-7 virus by an infected recruit upon arrival at the training base. Nosocomial transmission by close contacts was the most likely source leading to onset of the second HAdV-7 outbreak, establishing the apparent transmission link between the outbreaks. Our findings imply that in-hospital contact investigations should be encouraged to reduce or interrupt further spread of infectious agents when treating outbreak cases, and WGS can provide useful information guiding infection-control interventions.