Proof-of-Principle Study Suggesting Potential Anti-Inflammatory Activity of Butyrate and Propionate in Periodontal Cells

Abstract

Short-chain fatty acids (SCFAs) are potent immune modulators present in the gingival crevicular fluid. It is therefore likely that SCFAs exert a role in periodontal health and disease. To better understand how SCFAs can module inflammation, we screened acetic acid, propionic acid, and butyric acid for their potential ability to lower the inflammatory response of macrophages, gingival fibroblasts, and oral epithelial cells in vitro. To this end, RAW 264.7 and primary macrophages were exposed to LPSs from Porphyromonas gingivalis (P. gingivalis) with and without the SCFAs. Moreover, gingival fibroblasts and HSC2 oral epithelial cells were exposed to IL1β and TNFα with and without the SCFAs. We report here that butyrate was effective in reducing the lipopolysaccharide (LPS)-induced expression of IL6 and chemokine (C-X-C motif) ligand 2 (CXCL2) in the RAW 264.7 and primary macrophages. Butyrate also reduced the IL1β and TNFα-induced expression of IL8, chemokine (C-X-C motif) ligand 1 (CXCL1), and CXCL2 in gingival fibroblasts. Likewise, butyrate lowered the induced expression of CXCL1 and CXCL2, but not IL8, in HSC2 cells. Butyrate further caused a reduction of p65 nuclear translocation in RAW 264.7 macrophages, gingival fibroblasts, and HSC2 cells. Propionate and acetate partially lowered the inflammatory response in vitro but did not reach the level of significance. These findings suggest that not only macrophages, but also gingival fibroblasts and oral epithelial cells are susceptive to the anti-inflammatory activity of butyrate.

Disordered GPR43/NLRP3 expression in peripheral leukocytes of patients with atrial fibrillation is associated with intestinal short chain fatty acids levels

“…Moreover, lower SCFAs concentrations are found in circulation compared to the gut, with acetic acid, butyric acid, and propionic acid concentrations ranging 19–160, 1–13, and 1–12 µmol/L, respectively [ 45 , 46 ]. Similar to most studies, the human THP-1 cells were exposed to mM-range concentrations of SCFAs in the current study, with consistent findings that SCFAs treatment decreased the LPS-induced production of inflammatory factors [ 47 , 48 ]. Notably, Qi Hui et al revealed the anti-inflammatory effect of 20 μmol/L butyrate on LPS-induced human peripheral blood mononuclear cells [ 49 ].…”

Butyrate limits human natural killer cell effector function

“…Similar results were observed in macrophages, where propionate and butyrate but not acetate strongly inhibited inflammatory response 23 . Interestingly, butyrate and propionate also possess anti-inflammatory properties in other cell types such as iPSC-derived intestinal epithelia and periodontal tissue 24 , 25 . Butyrate was found to be the SCFA with the most consistent effects on NK cell metabolism and activation receptors at the concentrations used (1 mM, 2.5 mM and 5 mM).…”

Insight into the Causal Relationship between Gut Microbiota and Back Pain: A Two Sample Bidirectional Mendelian Randomization Study

“…[ 52 ] Butyrate was effective in reducing the lipopolysaccharide (LPS)‐induced expression of IL6 and chemokine (C‐X‐C motif) ligand 2 (CXCL2) in the macrophages. [ 53 ] Butyrate exerts anti‐inflammatory role by inhibiting the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐kappa B) signaling pathway. [ 54 ] The mechanisms by which intestinal microbiota play beneficial or detrimental roles in immune‐mediated back pain remain to be further investigated.…”