Mucosal microbiomes and Fusobacterium genomics in Vietnamese colorectal cancer patients

Abstract

Perturbations in the gut microbiome have been linked to the promotion and prognosis of colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite the increasing health burden inflicted by CRC in low- and middle-income countries like Vietnam, the CRC-specific microbiome in these populations remains underexplored. Here we conducted a study in Vietnam to enrol 43 CRC patients (cases) and 25 patients with non-cancerous colorectal polyps (controls) between December 2018 and January 2020. Our study investigated the mucosal microbiome signature and genomic diversity of Fusobacterium in Vietnamese CRC patients, using a combination of 16S rRNA gene profiling, anaerobic microbiology, and whole genome sequencing. We found that several oral bacteria, including F. nucleatum and Leptotrichia, were significantly more abundant in the tumour mucosa, and these two bacteria were also more enriched in tumours of advanced CRC stages (III-IV). We obtained 53 Fusobacterium genomes from the saliva, tumour and non-tumour mucosa of six CRC patients. Isolates from the gut mucosa belonged to diverse F. nucleatum subspecies (nucleatum, animalis, vincentii, polymorphum) and a potential new subspecies of F. periodonticum. The Fusobacterium population within each individual was distinct and in many cases diverse, with minimal intra-clonal variation. Phylogenetic analyses showed that within each individual, tumour-associated Fusobacterium were clonal to those isolated from non-tumour mucosa, but distantly related to those isolated from saliva. Genes encoding major virulence factors (Fap2 and RadD) showed variability in length and evidence of horizontal gene transfer. Our work provides a framework to understand the genomic diversity of Fusobacterium within the CRC patients, which can be exploited for the development of CRC diagnostic and therapeutic options targeting this oncobacterium.

Updated estimation of the burden of fungal disease in Vietnam

“… 37 Using international data, indicating that typically around 2.5% of adult asthmatics have ABPA, we estimated 74,658 cases per year. 22 , 38 , 39 Assuming that fungal sensitisation occurs in 33% of the worst 10% adult asthmatics, SAFS was anticipated to affect 98,549 cases annually (102.4/100,000). 22 , 40 …”

“… 22 , 38 , 39 Assuming that fungal sensitisation occurs in 33% of the worst 10% adult asthmatics, SAFS was anticipated to affect 98,549 cases annually (102.4/100,000). 22 , 40 …”

Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia

“…A 2016 Cochrane systematic review of 1337 participants (with 469 deaths) diagnosed with TBM from nine trials concluded that corticosteroids in combination with ATT reduced deaths by nearly one quarter (risk ratio = 0.75, 95% confidence interval = 0.65 to 0.87; highquality evidence) in the short term; however, no difference was found in the rate of disabling neurological deficits [75]. However, in a long-term follow-up study, dexamethasone did not improve the 5-year mortality rate in patients with severe TBM [76]. Corticosteroids reduce meningeal inflammation and cerebral edema, as well as restore vascular permeability [4,75].…”

Regulatory effects of oral microbe on intestinal microbiota and the illness

“…Transferring from saliva to the lower GI tract, the species diversity and abundance of F. nucleatum gradually dropped, indicating they resisted the selective stomach pressure ( Richardson et al., 2020 ). Several F. nucleatum subspecies ( nucleatum, animalis, vincentii, polymorphum ) and potential new subspecies are isolated from the intestine of colorectal cancer patients, and the major encoding virulence factors for F. uncleatum showed evidence of horizontal gene transfer ( Tran et al., 2022 ). Furthermore, intraperitoneal injection successfully established colonization of F. nucleatum in CRC tissue, which suggested the translocation of F. nucleatum through hematogenous route ( Abed et al., 2020 ).…”