Abstract
The intestinal microbiota is well known to have multiple benefits on human health, including cancer prevention and treatment. The effects are partially mediated by microbiota-produced short chain fatty acids (SCFAs) such as butyrate, propionate and acetate. The anti-cancer effect of butyrate has been demonstrated in cancer cell cultures and animal models of cancer. Butyrate, as a signaling molecule, has effects on multiple signaling pathways. The most studied effect is its inhibition on histone deacetylase (HDAC), which leads to alterations of several important oncogenic signaling pathways such as JAK2/STAT3, VEGF. Butyrate can interfere with both mitochondrial apoptotic and extrinsic apoptotic pathways. In addition, butyrate also reduces gut inflammation by promoting T-regulatory cell differentiation with decreased activities of the NF-κB and STAT3 pathways. Through PKC and Wnt pathways, butyrate increases cancer cell differentiation. Furthermore, butyrate regulates oncogenic signaling molecules through microRNAs and methylation. Therefore, butyrate has the potential to be incorporated into cancer prevention and treatment regimens. In this review we summarize recent progress in butyrate research and discuss the future development of butyrate as an anti-cancer agent with emphasis on its effects on oncogenic signaling pathways. The low bioavailability of butyrate is a problem, which precludes clinical application. The disadvantage of butyrate for medicinal applications may be overcome by several approaches including nano-delivery, analogue development and combination use with other anti-cancer agents or phytochemicals.
Highlights
The microbiome has evolved with the human host in a co-dependent manner, with mutual beneficial effects
In this review we summarize recent progress in butyrate research and discuss the future development of butyrate as an anti-cancer agent with emphasis on its effects on oncogenic signaling pathways
The role of the commensal bacteria in cancer immunotherapy was further confirmed by the experiment in mice which showed that fecal microbiome transplantation (FMT) from responding patients to germ-free mice increased the responses to anti-PD-L1 treatment [17]
Summary
The microbiome has evolved with the human host in a co-dependent manner, with mutual beneficial effects. Gut commensal bacteria can produce vitamins for the host, limit pathogenic bacterial over–growth, stimulate immune responses and secrete SCFAs such as acetate, butyrate and propionate [6]. Major discoveries have reported that the gut microbiota is closely associated with cancer immunotherapy, greatly improving patient responses to anti-immune checkpoint agents [10,11,12,13,14,15,16]. The role of the commensal bacteria in cancer immunotherapy was further confirmed by the experiment in mice which showed that fecal microbiome transplantation (FMT) from responding patients to germ-free mice increased the responses to anti-PD-L1 treatment [17]. FMT from non-responding patients to germ-free mice did not increase anti-PD-1/anti-PD-L1 efficacy in mice but it did if Akkermansia muciniphila was administered after FMT, further demonstrating the effect of the bacterial strain. We summarize how butyrate exerts anti-cancer effects through modulation of intracellular signaling pathways and discuss the potential implication of butyrate in cancer prevention and treatments as well as associated problems
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
