The colon microbiota is an important player in the development of colorectal cancer (CRC), which caused 935,000 deaths in 2020 (the second most deadly cancer worldwide).
During carcinogenesis, the colon microbiota composition changes from a normal profile to dysbiosis, interfering with the production of short-chain fatty acids (SCFAs), which have anti-cancer effects. In addition to other anti-cancer properties, specific strains of probiotics produce SCFAs that target colon cancer cells, offering a promising new therapy. This article will focus on recent research attempting to identify probiotics best suited to the task.
SCFAs and Colon Cancer
SCFAs are small molecules generated via the fermentation of dietary fibers by gut microbiota. Acetic, propionic, and butyric acid comprise the majority of colonic SCFA content.
Numerous studies have shown that SCFAs affect the regulation of inflammation, carcinogenesis, and intestinal barrier function.
Among the SCFA metabolites, butyrate (one of the main energy sources for colon cells) has been shown to play a key role in the prevention and treatment of colon cancer by promoting the cell-cycle arrest and cell apoptosis (programmed death) of cancer and stimulating immunomodulation. One mechanism by which butyrate inhibits cancer cell growth has been attributed to normal colon cells using butyrate as their primary energy source, whereas cancerous colonocytes rely on glucose.
Indeed, patients with CRC have exhibited a marked reduction in butyrate-producing bacteria and an increase in the pathogens associated with CRC, especially Fusobacterium nucleatum.
A recent systematic review and meta-analysis of 23 studies reported a significantly lower concentration of the three primary fecal SCFAs in individuals at risk of developing CRC compared to healthy subjects. In another study, an inverse correlation was found between fecal butyrate and tumor size in CRC.
Therefore, alteration in SCFA levels may impact the colonic health and predisposition of colonocytes to aberrant proliferation and tumor formation.
Modulation of the intestinal microbiota composition towards more favorable species for SCFA production is one strategy for improving CRC prevention and/or outcomes. (Oral administration of butyrate is not thought to be optimum due to its rancid smell and unpleasant taste). While dietary fibers and undigested proteins are also candidates to induce modulation, only probiotics will be further discussed here.
Probiotics and Colon Cancer
Studies have reported that certain probiotic strains produce SCFAs; however, different strains yield different amounts of SCFAs.
A recent study sought to characterize the relative SCFA production by specific strains of Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, Lacticaseibacillus rhamnosus, and Lacticaseibacillus rhamnosus.
Results showed that all the tested strains produced butyrate at different levels; however, the strains of L. paracasei and L. rhamnosus were stronger butyrate producers compared to the others. Findings revealed that butyrate production depended on the type of strain, the temperature, and the incubation period during cultivation.
The functions of the SCFAs were further characterized: the SCFAs exerted a positive anti-cancer effect in the colon via various actions, including inhibiting the growth of the pathogens related to colon cancer; suppressing the growth of cancer cells; stimulating the production of the anti-inflammatory cytokines; suppressing pathogen-stimulated pro-inflammatory cytokines.
Other probiotic strains will likely also show promise as relevant SCFAs producers for use as potential therapies against CRC.
Colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. This is in spite of widespread, effective measures of preventive screening and also major advances in treatment options.
SCFAs —especially butyrate—are specific towards colon cancer cells, showing promising therapeutic effects. Alteration in SCFA levels in the gut could impact the colonic health and predisposition of colon cells to aberrant proliferation and tumor formation. Amassing research reveals that probiotics can beneficially produce SCFAs, with some probiotic strains yielding more than others.
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