Evaluating the Role of Probiotics in the Prevention and Management of Age-Related Diseases.

The human lifespan has been significantly increased due to scientific advancements in the management of disease; however, the health span of the aging population does not follow the same trend. Aging is the major risk factor for multimorbidity that is derived from the progressive loss of homeostasis, immunological and stem cell exhaustion, as well as exacerbated inflammation responses. Age-related diseases presenting with high frequencies include neurodegenerative, musculoskeletal, cardiovascular, metabolic diseases and cancer. These diseases can be co-morbid and are usually managed using a disease-specific approach that can eventually lead to polypharmacy, low medication adherence rates and undesired drug-drug interactions. Novel studies suggest targeting the shared biological basis of age-related diseases to retard the onset and manage their manifestations. Harvesting the anti-inflammatory and immunomodulatory capacity of probiotics to tackle the root cause of these diseases, could pose a viable alternative. In this article, a comprehensive review of the effects of probiotic supplementation on the molecular pathogenesis of age-related diseases, and the potential of probiotic treatments as preventative or alleviatory means is attempted. Furthermore, issues on the safety and efficiency of probiotic supplementation, as well as the pitfalls of current clinical studies are discussed, while new perspectives for systematic characterization of probiotic benefits on aged hosts are outlined.

The Role of the Gut Microbiome in Cancer Immunotherapy: Current Knowledge and Future Directions.

Cancer immunotherapy is a treatment modality that aims to stimulate the anti-tumor immunity of the host to elicit favorable clinical outcomes. Immune checkpoint inhibitors (ICIs) gained traction due to the lasting effects and better tolerance in patients carrying solid tumors in comparison to conventional treatment. However, a significant portion of patients may present primary or acquired resistance (non-responders), and thus, they may have limited therapeutic outcomes. Resistance to ICIs can be derived from host-related, tumor-intrinsic, or environmental factors. Recent studies suggest a correlation of gut microbiota with resistance and response to immunotherapy as well as with the incidence of adverse events. Currently, preclinical and clinical studies aim to elucidate the unique microbial signatures related to ICI response and anti-tumor immunity, employing metagenomics and/or multi-omics. Decoding this complex relationship can provide the basis for manipulating the malleable structure of the gut microbiota to enhance therapeutic success. Here, we delve into the factors affecting resistance to ICIs, focusing on the intricate gut microbiome-immunity interplay. Additionally, we review clinical studies and discuss future trends and directions in this promising field.