Biological effects / Functions & Succinate / Succinic acid

Succinate / Succinic acid in the intestinal lumen plays a crucial role in immune response and cellular differentiation. Here is a detailed breakdown of its functions and interactions:

• Succinate / Succinic acid triggers the production of Interleukin-25 (IL-25) by chemosensory tuft cells.


• Interleukin-17E (IL-17E) / Interleukin-25 (IL-25) activates the expression of Interleukin-13 (IL-13) by Group 2 Innate Lymphoid Cells (ILC2).


• Interleukin-13 (IL-13) signals back to tuft cells, promoting their differentiation.

Succinate is not only produced by the host and microbiota but also by intestinal Parasites / Parasitism. This metabolite stimulates Interleukin-17E (IL-17E) / Interleukin-25 (IL-25) production by tuft cells, further influencing the immune response.

Additionally, succinate, a component of the citric acid cycle, modulates dendritic cell (DC) function by signaling through the extracellular Succinate receptor 1 (SUCNR1).

Succinate's interaction with IL-25 and IL-13 highlights its significant role in the immune system and cellular processes within the intestinal environment.

References:
Hill & Artis 2010
Nadjsombati et al. 2018 Immunity 49: 33-41 e37.
Schneider et al. 2018 Cell 174: 271-284 e214.
Fernández-Veledo & Vendrell 2019 Reviews in Endocrine and Metabolic Disorders 20: 439-447
McFarland & Colonna 2020

When mice were placed on a high-fiber diet, succinate produced by the microbiota increased and improved glucose and insulin tolerance
De Vadder et al. 2016 Cell Metab 24: 151-157

see also:
Group 2 ILCs (ILC2) & Interleukin-17E (IL-17E) / Interleukin-25 (IL-25)
Parasitic Infections & Tuft Cells