Use of Short-Chain Fatty Acids for the Recovery of the Intestinal Epithelial Barrier Affected by Bacterial Toxins

Short-chain fatty acids (SCFAs) are carboxylic acids produced as a result of gut microbial anaerobic fermentation. They activate signaling cascades, acting as ligands of G-protein-coupled receptors, such as GPR41, GPR43, and GPR109A, that can modulate the inflammatory response and increase the intestinal barrier integrity by enhancing the tight junction proteins functions. These junctions, located in the most apical zone of epithelial cells, control the diffusion of ions, macromolecules, and the entry of microorganisms from the intestinal lumen into the tissues. In this sense, several enteric pathogens secrete diverse toxins that interrupt tight junction impermeability, allowing them to invade the intestinal tissue and to favor gastrointestinal colonization. It has been recently demonstrated that SCFAs inhibit the virulence of different enteric pathogens and have protective effects against bacterial colonization. Here, we present an overview of SCFAs production by gut microbiota and their effects on the recovery of intestinal barrier integrity during infections by microorganisms that affect tight junctions. These properties make them excellent candidates in the treatment of infectious diseases that cause damage to the intestinal epithelium.

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The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity

PLoS ONE ◽

10.1371/journal.pone.0220642 ◽

2019 ◽

Vol 14 (8) ◽

pp. e0220642 ◽

Cited By ~ 9

Author(s):

Yuliia Holota ◽

Taisa Dovbynchuk ◽

Izumi Kaji ◽

Igor Vareniuk ◽

Natalia Dzyubenko ◽

...

Keyword(s):

Fatty Acids ◽

Antibiotic Therapy ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Barrier Integrity ◽

Intestinal Barrier Integrity ◽

Long Term Consequences

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Kidneys and microbiota

Ukrainian Journal of Nephrology and Dialysis ◽

10.31450/ukrjnd.1(65).2020.07 ◽

2019 ◽

pp. 48-57

Author(s):

Zh. Semydotska ◽

I. Chernyakova ◽

O. Avdeyeva

Keyword(s):

Chronic Kidney Disease ◽

Fatty Acids ◽

Kidney Disease ◽

Intestinal Microbiota ◽

General Circulation ◽

Short Chain Fatty Acids ◽

Uremic Toxins ◽

Short Chain ◽

Intestinal Lumen ◽

Chain Fatty Acids

The review article analyzes the results of studies of the bi-directional relationship of the intestinal microbiota and kidneys, the so-called colorenal interactive axis of interaction. The intestinal microbiota is considered as a kind of organ that influences the brain, cardiovascular and immune systems, as well as the kidneys of the "host". Short-chain fatty acids (SCFA) formed in the colon as the result of microbial metabolism from plant components of dietary fiber and acting as ligands for the olfactory receptor, paired G-proteins in the kidneys are recognized as the markers of this symbiosis. With the help of modern omix technologies, the development of dysbiosis taking into account patients with chronic kidney disease (CKD) has been proved, which leads to the accumulation of precursors of uremic toxins, a decrease in the production of SCFA, which have nephroprotective properties and play a key role in energy homeostasis. Changes in the composition of the intestinal microbiota in CKD, an increase in the content of uremic toxins in the intestinal lumen contribute to the appearance of the “leaky” intestinal barrier syndrome, the movement of bacteria from the intestine into the general circulation, the development of systemic inflammation, oxidative stress, comorbidity, the progression of CKD, and an increase in mortality. Diets with restriction of protein and potassium quotas, violation of nutritional status lead to the development of dysbiosis in CKD. A decrease in the diet of vegetables and fruit causes the expansion of bacteria producing uricase and urease, which are enzymes in the formation of uremic toxins and reduce the number and variety of bacteria producing short-chain fatty acids. Potential targeted effects on the axis of “intestinal microbiota - chronic kidney disease” are being discussed: the use of a diet enriched in plant fibers, heat-treated, then chilled potatoes and rice as prebiotics (sources of resistant starch), nuts, plant seeds, and pro-, pre-, synbiotics, fecal transplantation. Most of the proposed interventions in the structure and functions of the microbiota are not dangerous, side effects are minimal.

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1019 – Disrupted Circadian Oscillation of Gut-Derived Short Chain Fatty Acids in Shift Workers: Possible Mechanism for Loss of Resilancy of Intestinal Barrier in Disrupted Host

Gastroenterology ◽

10.1016/s0016-5085(19)37351-2 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-221-S-222

Author(s):

Garth Swanson ◽

Maliha Shaikh ◽

Louis Fogg ◽

Christopher B. Forsyth ◽

Ali Keshavarzian

Keyword(s):

Fatty Acids ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Circadian Oscillation ◽

Shift Workers ◽

Chain Fatty Acids

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Disrupted diurnal oscillation of gut-derived Short chain fatty acids in shift workers drinking alcohol: Possible mechanism for loss of resiliency of intestinal barrier in disrupted circadian host

Translational Research ◽

10.1016/j.trsl.2020.04.004 ◽

2020 ◽

Vol 221 ◽

pp. 97-109 ◽

Cited By ~ 1

Author(s):

Garth R. Swanson ◽

Joel Siskin ◽

Annika Gorenz ◽

Maliha Shaikh ◽

Shohreh Raeisi ◽

...

Keyword(s):

Fatty Acids ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Drinking Alcohol ◽

Shift Workers ◽

Diurnal Oscillation ◽

Chain Fatty Acids

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The interaction among gut microbes, the intestinal barrier and short chain fatty acids

Animal Nutrition ◽

10.1016/j.aninu.2021.09.012 ◽

2021 ◽

Author(s):

Jiayu Ma ◽

Xiangshu Piao ◽

Shad Mahfuz ◽

Shenfei Long ◽

Jian Wang

Keyword(s):

Fatty Acids ◽

Intestinal Barrier ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Gut Microbes ◽

Chain Fatty Acids

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Microbiota-derived metabolites, short chain-fatty acids, induce epigenetic modifications in CD4+ T cells in mice

Revista dos Trabalhos de Iniciação Científica da UNICAMP ◽

10.20396/revpibic2620181179 ◽

2019 ◽

Author(s):

Raissa Carolina Alves da Silva ◽

Marco Aurelio Ramirez Vinolo ◽

Laís Passarielo Pral ◽

José Luis Fachi

Keyword(s):

Fatty Acids ◽

T Cells ◽

Regulatory T Cells ◽

Short Chain Fatty Acids ◽

Host Cells ◽

Short Chain ◽

Intestinal Lumen ◽

Host Interaction ◽

Key Aspects ◽

Chain Fatty Acids

The gut microbiota is indispensable for the host, considering its role in regulating key aspects of host homeostasis, such as development, function and induction of T cells. One of the possibilities for microbiota-host interaction is through short-chain fatty acids (SCFAs). compounds produced by fermentation of dietary fiber of intestinal lumen bacteria. These compounds can regulate gene expression, by promoting inhibition of histone deacetylase enzimes (HDACs) and activation of histone acetyltransferases enzimes (HATs), thus increasing post-translational modifications such as acetylation and crotonylation. However, details of how these two types of modifications act on host cells, especially regulatory T cells, remains to be seen. Therefore, our aim was to evaluate the SCFA mediated role of microbiota on acetylation and crotonylation of regulatory T cells, as to verify how these two modifications can interact in the histone modification scenario. In conclusion, acetylation and crotonylation, linked to microbiota, have the potential to form an importante part in regulation of T CD4+ cells and can interact and modify directly the action of HDAC enzimes, which is notably relevant to microbiota-host interface.

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