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Review
. 2023 Oct 6:14:1171834.
doi: 10.3389/fimmu.2023.1171834. eCollection 2023.

Protein modification by short-chain fatty acid metabolites in sepsis: a comprehensive review

Liang Zhang  1   2   3 , Xinhui Shi  1   2   3 , Hongmei Qiu  1   2   3 , Sijia Liu  1   2   3 , Ting Yang  1   2   3 , Xiaoli Li  1   2   3 , Xin Liu  4
Affiliations
Review

Protein modification by short-chain fatty acid metabolites in sepsis: a comprehensive review

Liang Zhang et al. Front Immunol. .

Abstract

Sepsis is a major life-threatening syndrome of organ dysfunction caused by a dysregulated host response due to infection. Dysregulated immunometabolism is fundamental to the onset of sepsis. Particularly, short-chain fatty acids (SCFAs) are gut microbes derived metabolites serving to drive the communication between gut microbes and the immune system, thereby exerting a profound influence on the pathophysiology of sepsis. Protein post-translational modifications (PTMs) have emerged as key players in shaping protein function, offering novel insights into the intricate connections between metabolism and phenotype regulation that characterize sepsis. Accumulating evidence from recent studies suggests that SCFAs can mediate various PTM-dependent mechanisms, modulating protein activity and influencing cellular signaling events in sepsis. This comprehensive review discusses the roles of SCFAs metabolism in sepsis associated inflammatory and immunosuppressive disorders while highlights recent advancements in SCFAs-mediated lysine acylation modifications, such as substrate supplement and enzyme regulation, which may provide new pharmacological targets for the treatment of sepsis.

Keywords: immunity; inflammation; protein post-translational modifications (PTMs); sepsis; short-chain fatty acids (SCFAs).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
An overview on the effects of SCFAs on signaling pathways and protein post-translational modifications during LPS or TNFα-induced sepsis.
See this image and copyright information in PMC

References

    1. Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet (2018) 392(10141):75–87. doi: 10.1016/s0140-6736(18)30696-2 - DOI - PubMed
    1. van Vught LA, Klein Klouwenberg PM, Spitoni C, Scicluna BP, Wiewel MA, Horn J, et al. Incidence, risk factors, and attributable mortality of secondary infections in the intensive care unit after admission for sepsis. Jama (2016) 315(14):1469–79. doi: 10.1001/jama.2016.2691 - DOI - PubMed
    1. van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immunity (2021) 54(11):2450–64. doi: 10.1016/j.immuni.2021.10.012 - DOI - PubMed
    1. Domínguez-Andrés J, Novakovic B, Li Y, Scicluna BP, Gresnigt MS, Arts RJW, et al. The itaconate pathway is a central regulatory node linking innate immune tolerance and trained immunity. Cell Metab (2019) 29(1):211–220.e215. doi: 10.1016/j.cmet.2018.09.003 - DOI - PubMed
    1. Spitzer JJ, Bagby GJ, Mészáros K, Lang CH. Alterations in lipid and carbohydrate metabolism in sepsis. JPEN J Parenter Enteral Nutr (1988) 12(6 Suppl):53s–8s. doi: 10.1177/014860718801200604 - DOI - PubMed

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