Table 2.

Regulation of protein post-translational modifications by SCFAs in sepsis.

SCFAs	Histone/non-histone	PTMs changes	Model	Roles	Ref
Acetate	NIP45	Methylation	T-cell	Acetate alters DNA methylation in the region of activated Treg cells, regulates Treg cell proliferation and enhances the anti-inflammatory effect of immune cells.	(109)
Acetate	Foxp3 H3K9ac	Acetylation	T-cell	Acetate may increase acetylation of the Foxp3 promoter through HDAC9 inhibition by increasing the number and function of T regulatory cells and significant airway inflammatory responses.	(117)
Acetate	p70-S6K	Acetylation	T-cell	The inhibitory effect of SCFA on HDAC in T-cells increases acetylation of p70 S6 kinase and promotes T-cell differentiation into effector and regulatory T-cells, thereby promoting immunity or immune tolerance depending on the immune environment.	(120)
propionate	H3K9ac	Acetylation	cTregs	Propionic acid treatment of cTregs enhanced histone H3K9ac through inhibition of HDAC, which in turn affected the immune status of cTregs.	(115)
Pentanoate	H4	Acetylation	Th17 cell	Pentanoate promotes histone H4 acetylation by providing acetyl coenzyme A and inhibiting the activity of HDAC, induces IL-10 production by lymphocytes by increasing acetylation at the IL-10 promoter, and improves anti-inflammatory capacity.	(119)
Butyrate	H3	Acetylation	CD4+ T cells	Exogenous addition of butyrate enhances histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, induces differentiation of mouse colonic T-cells and ameliorates the development of colitis.	(118)
Butyrate	H3K9ac/ H3K9me3	Acetylation	CD4+ T cells	Butyrate protects the host from inflammation by increasing the binding of HIF1α to the IL-22 promoter through histone modifications and promoting IL-22 production.	(121)
Butyrate	H3K9ac	Acetylation	BMDM	Butyrate maintains tolerance to intestinal microbiota by inhibiting the activity of HDAC, promoting Nos2, IL-6 and H3K9ac, the promoter region of the IL12b gene, and by down-regulating the release of pro-inflammatory factors that reduce the response of macrophages to commensal bacteria.	(7)
Butyrate	GPR41/ GPR43	Methylation	Cecal Tissues	Butyrate inhibits the methylation of the GPR41/43 promoter region and thus the expression of GPR41/43, reducing inflammatory damage.	(103)
Butyrate	H3K18cr	Crotonylation	Colon epithelial cell	Butyrate promotes histone crotonylation by inhibiting the activity of HDAC in colonic epithelial cells.	(129)
Butyrate/ Propionate	Foxp3	Acetylation	peripheral regulatory T-cell	Butyrate and propionate increase acetylation of Foxp3 to promote extrathymic Treg cell differentiation by inhibiting HDAC activity.	(104)
Butyrate/ Propionate	H4K12ac	Acetylation	BMDM	Treatment of bone marrow cells with butyrate and propionate resulted in upregulation of H4K12ac on the PU.1 promoter, inhibiting the expression of PU.1 and RelB and thus preventing DC development.	(111)
isobutyric/ propionic	H3K27ac/ H3K27me3	Acetylation	T-cell	SCFAs regulates host antiviral innate immune response by increasing histone acetylation and decreasing repressive histone methylation to coordinate viral transcriptional activation.	(116)