Role of the microbiome in non-gastrointestinal cancers

"The forgotten organ",the human microbiome,comprises a community of microorganisms that colonizes various sites of the human body.Through coevolution of bacteria,archaea and fungi with the human host over thousands of years,a complex host-microbiome relationship emerged in which many functions,including metabolism and immune responses,became codependent.This coupling becomes evident when disruption in the microbiome composition,termed dysbiosis,is mirrored by the development of pathologies in the host.Among the most serious consequences of dysbiosis,is the development of cancer.As many as 20% of total cancers worldwide are caused by a microbial agent.To date,a vast majority of microbiomecancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers.Here,we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers,while distinguishing between viral and bacterial drivers of cancer,as well as "local" and "systemic","cancer-stimulating" and "cancer-suppressing" effects of the microbiome.Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis,and may enable to employ microbiome-targeting approaches as part of cancer treatment.

Phages and their potential to modulate the microbiome and immunity

Bacteriophages(hence termed phages)are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection.However,the molecular nature of phage interactions with bacteria and the human host has remained elusive for decades,limiting their therapeutic application.While many phages and their functional repertoires remain unknown,the advent of next-generation sequencing has increasingly enabled researchers to decode new lytic and lysogenic mechanisms by which they attack and destroy bacteria.Furthermore,the last decade has witnessed a renewed interest in the utilization of phages as therapeutic vectors and as a means of targeting pathogenic or commensal bacteria or inducing immunomodulation.Importantly,the narrow host range,immense antibacterial repertoire,and ease of manipulating phages may potentially allow for their use as targeted modulators of pathogenic,commensal and pathobiont members of the microbiome,thereby impacting mammalian physiology and immunity along mucosal surfaces in health and in microbiomeassociated diseases.In this review,we aim to highlight recent advances in phage biology and how a mechanistic understanding of phage-bacteria-host interactions may facilitate the development of novel phage-based therapeutics.We provide an overview of the challenges of the therapeutic use of phages and how these could be addressed for future use of phages as specific modulators of the human microbiome in a variety of infectious and noncommunicable human diseases.

Risk factors for non-alcoholic fatty liver disease delineate the battlegrounds in optimizing disease prevention

Multiple environmental factors impact non-alcoholic fatty liver disease(NAFLD).While the association with dietary habits and physical activity is broadly characterized(1),the contribution of socioeconomic disparities to these risk factors remains elusive to date(2).A cross-sectional study of the National Health and Nutrition Examination Surveys(NHANES)(3)recently examined a cohort representative of the adult U.S.population for combined effects of socio-demographic and lifestyle patterns on NAFLD risk behavior.Physical activity,a high-quality diet and higher education,but not income level,were found to reduce the risk of NALFD,irrespective of ethnicity or gender.As NAFLD is estimated to affect up to a quarter of the global population and particularly become more prevalent in industrialized countries(4),proper characterization of associated population-based risk factors is crucial in optimizing public health and educatory preventive and treatment directives.