A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei

Abstract

BackgroundPseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease.MethodsTo more clearly define the bacterial communities associated with PMP disease, we employed a sequenced-based analysis to profile the bacterial populations found in PMP tumor and mucin tissue in 11 patients. Sequencing data were confirmed by in situ hybridization at multiple taxonomic depths and by culturing. A pilot clinical study was initiated to determine whether the addition of antibiotic therapy affected PMP patient outcome.Main resultsWe determined that the types of bacteria present are highly conserved in all PMP patients; the dominant phyla are the Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. A core set of taxon-specific sequences were found in all 11 patients; many of these sequences were classified into taxonomic groups that also contain known human pathogens. In situ hybridization directly confirmed the presence of bacteria in PMP at multiple taxonomic depths and supported our sequence-based analysis. Furthermore, culturing of PMP tissue samples allowed us to isolate 11 different bacterial strains from eight independent patients, and in vitro analysis of subset of these isolates suggests that at least some of these strains may interact with the PMP-associated mucin MUC2. Finally, we provide evidence suggesting that targeting these bacteria with antibiotic treatment may increase the survival of PMP patients.ConclusionsUsing 16S amplicon-based sequencing, direct in situ hybridization analysis and culturing methods, we have identified numerous bacterial taxa that are consistently present in all PMP patients tested. Combined with data from a pilot clinical study, these data support the hypothesis that adding antimicrobials to the standard PMP treatment could improve PMP patient survival.

Comparative analysis of microbiome of bladder cancer patients

“…Its presence has been reported in an urothelial carcinoma study earlier [39] and in overactive bladder female samples [42]. Methylotenera detected in all samples in the present study ranged between 0.1-3.3% had been previously detected in a study on peritoneal tumors in humans along with multiple other genera [45].…”

The microbiome in chronic kidney disease patients undergoing hemodialysis and peritoneal dialysis

“…Therefore, alternative routes and factors have been recognized as responsible for peritonitis in PD patients, such as transvisceral microbial migration through the impaired intestinal barrier (e.g., bowel leak), hematogenous and vaginal leak [71]. Previous reports described bacterial DNA in PD effluent or peritoneum cells what supports this hypothesis [72][73][74][75]. In addition, the intracellular viability of S. aureus after sequestration by mesothelial cells was revealed in different studies, supporting this hypothesis [76,77].…”

Pseudomyxoma Peritonei

“…Possible new role of adjuvant systemic chemotherapy (FOLFOX4) in the treatment of PMP [82]; b. Potential applicability of ascorbic acid and hydrogen peroxide for mucolysis on compact mucin secreted in PMP [83]; c. Possible benefit of bevacizumab-based combination therapy in advanced cases in order to achieve disease stabilization and clinical improvement [84]; d. Recent studies highlight the possible role of bacteria in PMP disease: these data may support the hypothesis that adding antimicrobials to the standard PMP treatment could improve patient survival [85]; e. Potential application of anti-inflammatory drugs that seem to inhibit extracellular mucin production in PMP, decreasing compressive symptoms and increasing the disease-free interval [86]. In conclusion, immunohistochemical, genetic, and pharmacological studies may help our understanding and improve outcomes of a particular subset of or recurrent PMP.…”