Converging evidences showed that people with diabetes mellitus (DM) have significantly higher risk for different cancers, of which the exact mechanism underlying the association has not been fully realized. Short-chain fatty acids (SCFAs), the fermentation products of the intestinal microbiota, are an essential source for energy supply in gut epithelial cells. They have been reported to improve intestinal barrier integrity, prevent microbial translocation, and further dampen inflammation. Gut dysbiosis and reduction in SCFA-producing bacteria as well as SCFAs production in the intestine are commonly seen in metabolic disorders including DM and obesity. Moreover, inflammation can contribute to tumor initiation and progression through multiple pathways, such as enhancing DNA damage, accumulating mutations in tumor suppressor genes Tp53, and activating nuclear factor-kappa B (NF-κB) signaling pathways. Based on these facts, we hypothesize that lower levels of microbial SCFAs resulted from gut dysbiosis in diabetic individuals, enhance microbial translocation, and increase the inflammatory responses, inducing tumorigenesis ulteriorly. To this end, we will discuss protective properties of microbial SCFAs and explore the pivotal roles SCFAs played in the link of DM with cancer, so as to take early precautions to reduce the risk of cancer in patients with DM.

Myocardial fibrosis (MF) is a pathological process that accelerates cardiac remodeling in myocardial infarction (MI), and miR-29 has become one of the foci of research into MF. As an alkaloid extracted from Herba leonuri, leonurine (LE) has been found to be an effective natural active ingredient for inhibiting fibrosis in many preclinical experiments. However, whether LE protects against MF after MI through modifying miR-29 remains unclear. The present study aimed to investigate the therapeutic effects of LE on MF, and to elucidate the underlying mechanisms involved. A mouse model of MI was established, followed by administration of LE for 4 weeks. We found that LE effectively improved cardiac function, and attenuated fibrosis and cardiac remodeling in mice post-MI. In vitro, LE simultaneously inhibited proliferation and migration of neonatal mouse cardiac fibroblasts (CFs) exposed to angiotensin II (Ang II), and the activation of collagen synthesis and myofibroblast generation was markedly suppressed by LE. Notably, we found that all mature miR-29 family members were downregulated in the myocardial tissues of mice post-MI, whereas LE significantly upregulated miR-29a-3p expression, and such upregulation was also detected in LE-treated CFs under Ang II stimulation. Knockdown of miR-29a-3p by a specific miRNA inhibitor upregulated the protein levels of TGF-β, collagen III, and collagen I in CFs, and completely reversed the antifibrotic effects of LE on CFs. Our study suggests that LE exerts cardioprotective effects against MF, possibly through the upregulation of miR-29a-3p.

Accumulating evidence indicates that patients with inflammatory bowel disease (IBD) have a significantly higher risk of developing different cancers, while the exact mechanism involved is not yet fully understood. Malassezia is a lipid-dependent opportunistic yeast, which colonizes on mammalian skin and internal organs. Also, dysbiosis in fungal communities accompanied by high level of Malassezia are fairly common in inflammatory diseases such as IBD and various cancers. In cancer patients, higher levels of Malassezia are associated with worse prognosis. Once it is ablated in tumor-bearing mice, their prognostic conditions will be improved. Moreover, Malassezia manifests multiple proinflammatory biological properties, such as destruction of epithelial barrier, enrichment of inflammatory factors, and degradation of extracellular matrix (ECM), all of which have been reported to contribute to tumor initiation and malignant progression. Based on these facts, we hypothesize that high levels of Malassezia together with mycobiome dysbiosis in patients with IBD, would aggravate the microecological imbalance, worsen the inflammatory response, and further promote tumorigenesis and deterioration. Herein, we will discuss the detrimental properties of Malassezia and explore the key role of this fungus in the correlation between IBD and cancer, in order to take early surveillance and intervention to minimize the cancer risk in individuals with IBD.