Gut Microbiota-Derived Short-Chain Fatty Acids: Impact on Cancer Treatment Response and Toxicities

Abstract

The gut microbiota has emerged as a key modulator of cancer treatment responses in terms of both efficacy and toxicity. This effect is clearly mediated by processes impacting the activation and modulation of immune responses. More recently, the ability to regulate chemotherapeutic drug metabolism has also emerged as a key driver of response, although the direct mechanisms have yet to be fully elucidated. Through fermentation, the gut microbiota can produce several types of metabolites, including short-chain fatty acids (SCFAs). SCFAs play an important role in maintaining epithelial barrier functions and intestinal homeostasis, with recent work suggesting that SCFAs can modulate response to cancer treatments and influence both anti-tumor immune response and inflammatory-related side effects. In this review, we will discuss the importance of SCFAs and their implications for cancer treatment response and toxicities.

Postoperative Probiotics Administration Attenuates Gastrointestinal Complications and Gut Microbiota Dysbiosis Caused by Chemotherapy in Colorectal Cancer Patients

“…Furthermore, specific changes in the gut metabolome have been presented in CRC subjects who underwent antitumor treatments, particularly in SCFAs [ 33 , 34 ]. Outside of regulating energy metabolism, SCFAs can also modulate the systemic immune response, inhibit the intestinal inflammatory reaction, and recover gut homeostasis for patients [ 13 ].…”

Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling

“…Short-chain Fatty acids (SCFAs), produced by the gut microbiome with the breakdown of nondigestible fibres, have now attained considerable attention as dietary supplementation having beneficial and therapeutic potential including in cancer treatment [57,58]. Recent studies have highlighted the role of short-chain fatty acids in gluconeogenesis, energy metabolism, immune modulation, and maintenance of epithelial barrier integrity in gut, and few suggest the existence of gut-brain and gut-lung axis crosstalk in SCFAs effect [59][60][61][62].…”

Alterations of Vaginal Microbiota and Chlamydia trachomatis as Crucial Co-Causative Factors in Cervical Cancer Genesis Procured by HPV

“…The vaginal microenvironment is a densely populated area in which local bacteria perform a great variety of bioactivities under the guide of specific gene expression that is in charge of the enzymes necessary for specific defenses and biotransformation [ 17 , 18 ]. In fact, patients affected by both colorectal cancer and CC showed lower levels of butyrate-agent producers in the local microbiota than healthy individuals, indicating an important shift in terms of local flora homeostasis [ 17 , 18 , 19 ].…”

“…In CC, a compromised microenvironment is mainly a consequence of deconstructed constituent parts of the vaginal microenvironment [ 26 , 27 ]. The intrinsic problems recall the simultaneous presence of multiple factors, such as the high inflammatory state, the presence of SNPs on genes that regulate the expression of immunosuppressive cytokines and interleukins, and a persistent local dysbiosis; these, in turn, facilitate the long-term aggressiveness of the HPV and Chlamydia infection [ 19 , 28 ]. The outcomes on the female genital tract, either on the vaginal or cervical microbiota, together with a substantial cytokine profile have identified the changes in microbiota diversity among women affected by HPV and C. trachomatis infection with bacteria/viral vaginosis (BVV) [ 28 , 29 , 30 , 31 ].…”