Short-Chain Fatty Acids Promote Immunotherapy by Modulating Immune Regulatory Property in B Cells

The dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis that modulates PA production alleviating airway allergy through maintaining Breg functions. B cells were isolated from the blood obtained from AR patients and healthy control (HC) subjects. The stabilization of IL-10 mRNA in B cells was tested with RT-qPCR. An AR mouse model was developed to test the role of PA in stabilizing the IL-10 expression in B cells. We found that the serum PA levels were negatively correlated with the serum Th2 cytokine levels in AR patients. Serum PA levels were positively associated with peripheral CD5+ B cell frequency in AR patients; the CD5+ B cells were also IL-10+. The spontaneous IL-10 mRNA decay was observed in B cells, which was prevented by the presence of PA through activating GPR43. PA counteracted the effects of Tristetraprolin (TTP) on inducing IL-10 mRNA decay in B cells through the AKT/T-bet/granzyme B pathway. Administration of Yupinfeng San, a Chinese traditional medical formula, or indole-3-PA, induced PA production by intestinal bacteria to stabilize the IL-10 expression in B cells, which promoted the allergen specific immunotherapy, and efficiently alleviated experimental AR. In summary, the data show that CD5+ B cells produce IL-10. The serum lower PA levels are associated with the lower frequency of CD5+ B cells in AR patients. Administration with Yupinfeng San or indole-3-PA can improve Breg functions and alleviate experimental AR.

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B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids

Nature Communications ◽

10.1038/s41467-019-13603-6 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 24

Author(s):

Helia N. Sanchez ◽

Justin B. Moroney ◽

Huoqun Gan ◽

Tian Shen ◽

John L. Im ◽

...

Keyword(s):

Fatty Acids ◽

B Cells ◽

B Cell ◽

Dna Recombination ◽

Short Chain Fatty Acids ◽

Histone Deacetylation ◽

Antibody Responses ◽

Short Chain ◽

Autoantibody Production ◽

Chain Fatty Acids

AbstractShort-chain fatty acids (SCFAs) butyrate and propionate are metabolites from dietary fiber's fermentation by gut microbiota that can affect differentiation or functions of T cells, macrophages and dendritic cells. We show here that at low doses these SCFAs directly impact B cell intrinsic functions to moderately enhance class-switch DNA recombination (CSR), while decreasing at higher doses over a broad physiological range, AID and Blimp1 expression, CSR, somatic hypermutation and plasma cell differentiation. In human and mouse B cells, butyrate and propionate decrease B cell Aicda and Prdm1 by upregulating select miRNAs that target Aicda and Prdm1 mRNA-3′UTRs through inhibition of histone deacetylation (HDAC) of those miRNA host genes. By acting as HDAC inhibitors, not as energy substrates or through GPR-engagement signaling in these B cell-intrinsic processes, these SCFAs impair intestinal and systemic T-dependent and T-independent antibody responses. Their epigenetic impact on B cells extends to inhibition of autoantibody production and autoimmunity in mouse lupus models.

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Development of a HPLC–UV method for the quantitative determination of four short-chain fatty acids and lactic acid produced by intestinal bacteria during in vitro fermentation

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2013.02.032 ◽

2013 ◽

Vol 80 ◽

pp. 107-115 ◽

Cited By ~ 75

Author(s):

S. De Baere ◽

V. Eeckhaut ◽

M. Steppe ◽

C. De Maesschalck ◽

P. De Backer ◽

...

Keyword(s):

Fatty Acids ◽

Lactic Acid ◽

Quantitative Determination ◽

Intestinal Bacteria ◽

Short Chain Fatty Acids ◽

Short Chain ◽

In Vitro Fermentation ◽

Chain Fatty Acids

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Associations of serum short-chain fatty acids with circulating immune cells and serum biomarkers in patients with multiple sclerosis

Scientific Reports ◽

10.1038/s41598-021-84881-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Stephanie Trend ◽

Jonatan Leffler ◽

Anderson P. Jones ◽

Lilian Cha ◽

Shelley Gorman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Fatty Acids ◽

B Cells ◽

Immune Cells ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Bioactive Metabolites ◽

Healthy Controls ◽

Serum Factors ◽

Chain Fatty Acids

AbstractAltered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.

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