Gut dysbiosis: a potential link between increased cancer risk in ageing and inflammaging.
Biragyn A, Ferrucci L
Lancet Oncol. Jun 2018
COMMENT: Ageing reduces the diversity and density of beneficial commensals in the gut, which control pathogens and maintain intestinal barrier integrity through the production of mucus and lipid metabolites, such as short-chain fatty acids. In this paper the authors propose that age-related changes in the number of gut bacteria lead to dysbiosis and leakage of proinflammatory microbial products. In turn, this situation would dysregulate the function of myeloid cells to clear impaired and senescent cells, by, for example, impairing the ability of plasmacytoid dendritic cells to induce adaptive immune responses to neoantigens and by reducing phagocytosis of neutrophils, monocytes, and macrophages.
According to authors opinion:
Ageing is associated with a reduction in the beneficial commensal microbes, which control the expansion of pathogenic commensals and maintain the integrity of the intestinal barrier through the production of mucus and lipid metabolites, such as short-chain fatty acids. Expansion of gut dysbiosis and leakage of microbial products contributes to the chronic proinflammatory state (inflammaging), which negatively affects the immune system and impairs the removal of mutant and senescent cells, thereby enabling tumour outgrowth. Studies in animal models and the importance of commensals in cancer immunotherapy suggest that this status can be reversible. Thus, interventions that alter the composition of the gut microbiota might reduce inflammaging and rejuvenate immune functions to provide anticancer benefits in frail elderly people.
Further studies should seek to understand what metrics in the gut microbiome and immune status can be applied in clinical practice to predict cancer risk and outcomes of treatment in elderly people and to help advance our knowledge of the influence of the gut microbiota on ageing.