Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.

The polyamines putrescine, spermidine, and spermine are widely distributed polycationic compounds essential for cellular functions. Intracellular polyamine pools are tightly regulated by a complex regulatory mechanism involving de novo biosynthesis, catabolism, and transport across the plasma membrane. In mammals, both the production of polyamines and their uptake from the extracellular space are controlled by a set of proteins named antizymes and antizyme inhibitors. Dysregulation of polyamine levels has been implicated in a variety of human pathologies, especially cancer. Additionally, decreases in the intracellular and circulating polyamine levels during aging have been reported. The differences in the polyamine content existing among tissues are mainly due to the endogenous polyamine metabolism. In addition, a part of the tissue polyamines has its origin in the diet or their production by the intestinal microbiome. Emerging evidence has suggested that exogenous polyamines (either orally administrated or synthetized by the gut microbiota) are able to induce longevity in mice, and that spermidine supplementation exerts cardioprotective effects in animal models. Furthermore, the administration of either spermidine or spermine has been shown to be effective for improving glucose homeostasis and insulin sensitivity and reducing adiposity and hepatic fat accumulation in diet-induced obesity mouse models. The exogenous addition of agmatine, a cationic molecule produced through arginine decarboxylation by bacteria and plants, also exerts significant effects on glucose metabolism in obese models, as well as cardioprotective effects. In this review, we will discuss some aspects of polyamine metabolism and transport, how diet can affect circulating and local polyamine levels, and how the modulation of either polyamine intake or polyamine production by gut microbiota can be used for potential therapeutic purposes.

Prohormone convertase 1/3, encoded by the PCSK1 gene, is a serine endoprotease that is involved in the processing of a variety of proneuropeptides and prohormones. Humans who are homozygous or compound heterozygous for loss-of-function mutations in PCSK1 exhibit a variable and pleiotropic syndrome consisting of some or all of the following: obesity, malabsorptive diarrhea, hypogonadotropic hypogonadism, altered thyroid and adrenal function, and impaired regulation of plasma glucose levels in association with elevated circulating proinsulin-to-insulin ratio. Recently, more common variants in the PCSK1 gene have been found to be associated with alterations in body mass index, increased circulating proinsulin levels, and defects in glucose homeostasis. This review provides an overview of the endocrinopathies and other disorders observed in prohormone convertase 1/3-deficient patients, discusses the possible biochemical basis for these manifestations of the disease, and proposes a model whereby certain missense mutations in PCSK1 may result in proteins with a dominant negative action.