Anti-cancer and anti-inflammatory effects elicited by short chain fatty acids produced by Escherichia coli isolated from healthy human gut microbiota

Atchareeya Nakkarach,Sunee Nitisinprasert,Nur Elina Abdul Mutalib,Adelene Ai-Lian Song,Hooi Ling Foo,Ulaiwan Withayagiat

doi:10.1186/s12934-020-01477-z

Atchareeya Nakkarach, Sunee Nitisinprasert + Show 4 more

Open Access

https://doi.org/10.1186/s12934-020-01477-z

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Abstract

BackgroundExtracellular metabolites of short chain fatty acids (SCFA) excreted by gut microbiota have been reported to play an important role in the regulation of intestinal homeostasis. Apart from supplying energy, SCFA also elicit immune stimulation in animal and human cells. Therefore, an attempt was conducted to isolate SCFA producing bacteria from healthy human microbiota. The anti-cancer and anti-inflammatory effects of extracellular metabolites and individual SFCA were further investigated by using breast, colon cancer and macrophage cells. Toxin, inflammatory and anti-inflammatory cytokine gene expressions were investigated by RT-qPCR analyses in this study.ResultsEscherichia coli KUB-36 was selected in this study since it has the capability to produce seven SCFA extracellularly. It produced acetic acid as the main SCFA. It is a non-exotoxin producer and hence, it is a safe gut microbiota. The IC50 values indicated that the E. coli KUB-36 metabolites treatment elicited more potent cytotoxicity effect on MCF7 breast cancer cell as compared to colon cancer and leukemia cancer cells but exhibited little cytotoxic effects on normal breast cell. Furthermore, E. coli KUB-36 metabolites and individual SCFA could affect inflammatory responses in lipopolysaccharide-induced THP-1 macrophage cells since they suppressed inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α well as compared to the control, whilst inducing anti-inflammatory cytokine IL-10 expression.ConclusionSCFA producing E. coli KUB-36 possessed vast potential as a beneficial gut microbe since it is a non-exotoxin producer that exhibited beneficial cytotoxic effects on cancer cells and elicited anti-inflammatory activity simultaneously. However, the probiotic characteristic of E. coli KUB-36 should be further elucidated using in vivo animal models.

Highlights

Extracellular metabolites of short chain fatty acids (SCFA) excreted by gut microbiota have been reported to play an important role in the regulation of intestinal homeostasis
It was designated as E. coli KUB-36 since the alignment of the 16S rRNA gene demonstrated more than 99% sequence similarity to the NCBI deposited 16S rRNA genes of E. coli strains
The results showed that E. coli KUB-36 metabolites and individual SCFA that produced by E. coli KUB-36 metabolites have high suppression on the inflammatory cytokine IL-6 expression as compared to the control

Summary

Introduction

Extracellular metabolites of short chain fatty acids (SCFA) excreted by gut microbiota have been reported to play an important role in the regulation of intestinal homeostasis. One of the important metabolites that is produced by gut microbiota is short chain fatty acid (SCFA). Nakkarach et al Microb Cell Fact (2021) 20:36 are acetic, butyric and propionic (≥ 95%) acids, whereas formic, valeric, caproic acids, etc., make up the remaining SCFA [3], whereby they reduce the luminal pH, enhance the absorption of some nutrients and have direct impact on the gut microbiota composition [4]. Escherichia coli Nissle 1917, a Gram-negative bacterium that has been reported to be a probiotic bacterium produces SCFA as the end products of carbohydrate metabolism under anaerobic growth condition, with mainly acetic acid and some propionic and butyric acids [6]

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