Function Of Short-chain Fatty Acids Research Articles

The role of gut-derived short-chain fatty acids in Parkinson's disease.

The emerging function of short-chain fatty acids (SCFAs) in Parkinson's disease (PD) has been investigated in this article. SCFAs, which are generated via the fermentation of dietary fiber by gut microbiota, have been associated with dysfunction of the gut-brain axis and, neuroinflammation. These processes are integral to the development of PD. This article examines the potential therapeutic implications of SCFAs in the management of PD, encompassing their capacity to modulate gastrointestinal permeability, neuroinflammation, and neuronal survival, by conducting an extensive literature review. As a whole, this article emphasizes the potential therapeutic utility of SCFAs as targets for the management and treatment of PD.

Solid organ transplantation and gut microbiota: a review of the potential immunomodulatory properties of short-chain fatty acids in graft maintenance.

Transplantation is the treatment of choice for several end-stage organ defects: it considerably improves patient survival and quality of life. However, post-transplant recipients may experience episodes of rejection that can favor or ultimately lead to graft loss. Graft maintenance requires a complex and life-long immunosuppressive treatment. Different immunosuppressive drugs (i.e., calcineurin inhibitors, glucocorticoids, biological immunosuppressive agents, mammalian target of rapamycin inhibitors, and antiproliferative or antimetabolic agents) are used in combination to mitigate the immune response against the allograft. Unfortunately, the use of these antirejection agents may lead to opportunistic infections, metabolic (e.g., post-transplant diabetes mellitus) or cardiovascular (e.g., arterial hypertension) disorders, cancer (e.g., non-Hodgkin lymphoma) and other adverse effects. Lately, immunosuppressive drugs have also been associated with gut microbiome alterations, known as dysbiosis, and were shown to affect gut microbiota-derived short-chain fatty acids (SCFA) production. SCFA play a key immunomodulatory role in physiological conditions, and their impairment in transplant patients could partly counterbalance the effect of immunosuppressive drugs leading to the activation of deleterious pathways and graft rejection. In this review, we will first present an overview of the mechanisms of graft rejection that are prevented by the immunosuppressive protocol. Next, we will explain the dynamic changes of the gut microbiota during transplantation, focusing on SCFA. Finally, we will describe the known functions of SCFA in regulating immune-inflammatory reactions and discuss the impact of SCFA impairment in immunosuppressive drug treated patients.

The emerging roles of microbiome and short-chain fatty acids in the pathogenesis of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature infants and leads to long-term pulmonary complications. The pathogenesis of BPD has not been fully elucidated yet. In recent years, the microbiome and its metabolites, especially short-chain fatty acids (SCFAs), in the gut and lungs have been demonstrated to be involved in the development and progression of the disease. This review aims to summarize the current knowledge on the potential involvement of the microbiome and SCFAs, especially the latter, in the development and progression of BPD. First, we introduce the gut-lung axis, the production and functions of SCFAs, and the role of SCFAs in lung health and diseases. We then discuss the evidence supporting the involvement of the microbiome and SCFAs in BPD. Finally, we elaborate on the potential mechanisms of the microbiome and SCFAs in BPD, including immune modulation, epigenetic regulation, enhancement of barrier function, and modulation of surfactant production and the gut microbiome. This review could advance our understanding of the microbiome and SCFAs in the pathogenesis of BPD, which also helps identify new therapeutic targets and facilitate new drug development.

Regulation of dietary fiber on intestinal microorganisms and its effects on animal health.

The animal gut harbors diverse microbes that play an essential role in the well-being of their host. Specific diets, such as those rich in dietary fiber, are vital in disease prevention and treatment because they affect intestinal flora and have a positive impact on the metabolism, immunity, and intestinal function of the host. Dietary fiber can provide energy to colonic epithelial cells, regulate the structure and metabolism of intestinal flora, promote the production of intestinal mucosa, stimulate intestinal motility, improve glycemic and lipid responses, and regulate the digestion and absorption of nutrients, which is mainly attributed to short-chain fatty acids (SCFA), which is the metabolite of dietary fiber. By binding with G protein-coupled receptors (including GPR41, GPR43 and GPR109A) and inhibiting the activity of histone deacetylases, SCFA regulate appetite and glucolipid metabolism, promote the function of the intestinal barrier, alleviate oxidative stress, suppress inflammation, and maintain immune system homeostasis. This paper reviews the physicochemical properties of dietary fiber, the interaction between dietary fiber and intestinal microorganisms, the role of dietary fiber in maintaining intestinal health, and the function of SCFA, the metabolite of dietary fiber, in inhibiting inflammation. Furthermore, we consider the effects of dietary fiber on the intestinal health of pigs, the reproduction and lactation performance of sows, and the growth performance and meat quality of pigs.

Metabolism of gut microbiota and its role in state of diabetes mellitus

The number of new cases of diabetes mellitus (DM) and its complications is rapidly increasing and a great amount of cases remains undiagnosed. It demonstrates that improvement of existing methods of treatment can be extremely helpful in present situation. It is known, that one of components of pathogenesis of DM is gut microbiota (GM) and its metabolism. Metabolites of GM include short-chain fatty acids (SCFA), some gases, energy and some low molecular metabolites. From the point of influence on stage of diabetes mellitus SCFA are the most interest. They are not only the main source of energy for colonocytes with antiischemic and protective properties, concerning the gut wall, but they also increase satiety, reduce insulin resistance, improve β-cell function and lead to decrease in body mass. Functions of SCFA are so versatile that they can be mentioned in DM with relative and absolute insulin deficiency as well. Due to its plasticity, GM can change its structure and functions in response to some changes in organism. However, in people with DM these changes are severe and continuous, which makes total amount of microorganisms and their proportion change irreversibly, leading to associated changes in amount of SCFA. Considering the positive effects of SCFA on carbohydrate metabolism, modulation of GM metabolism may occur an efficient addition to antidiabetic therapy. One of the powerful factors, influencing GM, is dietary fiber (DF). They are an energetic substrate for GM, they also maintain pH necessary for GM and regulate food passage in gastrointestinal system. Studying the influence of SCFA on DM and correction of metabolic dysregulation with DF need special attention, as DF and SCFA may become a powerful addition to antidiabetic therapy.

Conjugated linoleic acids inhibit lipid deposition in subcutaneous adipose tissue and alter lipid profiles in serum of pigs.

Conjugated linoleic acids (CLAs) have served as a nutritional strategy to reduce fat deposition in adipose tissues of pigs. However, the effects of CLAs on lipid profiles in serum and how these lipid molecules regulate fat deposition are still unclear. In this study, we explored the effects of CLAs on regulating lipid deposition in adipose tissues in terms of lipid molecules and microbiota based on a Heigai pig model. A total of 56 Heigai finishing pigs (body weight: 85.58 ± 10.39 kg) were randomly divided into two treatments and fed diets containing 1% soyabean oil or 1% CLAs for 40 d. CLAs reduced fat deposition and affected fatty acids composition in adipose tissues of Heigai pigs via upregulating the expression of the lipolytic gene (hormone-sensitive lipase, HSL) in vivo and in vitro. CLAs also altered the biochemical immune indexes including reduced content of total cholesterol (TChol), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) and changed lipids profiles including decreased sphingolipids especially ceramides (Cers) and sphingomyelins (SMs) in serum of Heigai pigs. Mechanically, CLAs may decrease peroxisome proliferator-activated receptorγ (PPARγ) expression and further inhibit adipogenic differentiation in adipose tissues of pigs by suppressing the function of Cers in serum. Furthermore, Pearson's correlation analysis showed HSL expression was positively related to short-chain fatty acids (SCFAs) in the gut (P ≤ 0.05) but the abundance of Cers was negatively related to the production and functions of SCFAs (P ≤ 0.05). CLAs altered the distribution of the lipid in serum and inhibited adipogenic differentiation by suppressing the function of Cers and further decreasing PPARγ expression in adipose tissues of Heigai pigs. Besides, the HSL expression and the abundance of Cers are associated with the production and functions of SCFAs in the gut.

Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection

ABSTRACT The gut microbiome is intricately coupled with immune regulation and metabolism, but its role in Coronavirus Disease 2019 (COVID-19) is not fully understood. Severe and fatal COVID-19 is characterized by poor anti-viral immunity and hypercoagulation, particularly in males. Here, we define multiple pathways by which the gut microbiome protects mammalian hosts from SARS-CoV-2 intranasal infection, both locally and systemically, via production of short-chain fatty acids (SCFAs). SCFAs reduced viral burdens in the airways and intestines by downregulating the SARS-CoV-2 entry receptor, angiotensin-converting enzyme 2 (ACE2), and enhancing adaptive immunity via GPR41 and 43 in male animals. We further identify a novel role for the gut microbiome in regulating systemic coagulation response by limiting megakaryocyte proliferation and platelet turnover via the Sh2b3-Mpl axis. Taken together, our findings have unraveled novel functions of SCFAs and fiber-fermenting gut bacteria to dampen viral entry and hypercoagulation and promote adaptive antiviral immunity.

Biological Function of Short-Chain Fatty Acids and Its Regulation on Intestinal Health of Poultry.

Short-chain fatty acids (SCFAs) are metabolites generated by bacterial fermentation of dietary fiber (DF) in the hindgut. SCFAs are mainly composed of acetate, propionate and butyrate. Many studies have shown that SCFAs play a significant role in the regulation of intestinal health in poultry. SCFAs are primarily absorbed from the intestine and used by enterocytes as a key substrate for energy production. SCFAs can also inhibit the invasion and colonization of pathogens by lowering the intestinal pH. Additionally, butyrate inhibits the expression of nitric oxide synthase (NOS), which encodes inducible nitric oxide synthase (iNOS) in intestinal cells via the PPAR-γ pathway. This pathway causes significant reduction of iNOS and nitrate, and inhibits the proliferation of Enterobacteriaceae to maintain overall intestinal homeostasis. SCFAs can enhance the immune response by stimulating cytokine production (e.g. TNF-α, IL-2, IL-6, and IL-10) in the immune cells of the host. Similarly, it has been established that SCFAs promote the differentiation of T cells into T regulatory cells (Tregs) and expansion by binding to receptors, such as Toll-like receptors (TLR) and G protein-coupled receptors (GPRs), on immune cells. SCFAs have been shown to repair intestinal mucosa and alleviate intestinal inflammation by activating GPRs, inhibiting histone deacetylases (HDACs), and downregulating the expression of pro-inflammatory factor genes. Butyrate improves tight-junction-dependent intestinal barrier function by promoting tight junction (TJ) assembly. In recent years, the demand for banning antibiotics has increased in poultry production. Therefore, it is extremely important to maintain the intestinal health and sustainable production of poultry. Taking nutrition strategies is important to regulate SCFA production by supplementing dietary fiber and prebiotics, SCFA-producing bacteria (SPB), and additives in poultry diet. However, excessive SCFAs will lead to the enteritis in poultry production. There may be an optimal level and proportion of SCFAs in poultry intestine, which benefits to gut health of poultry. This review summarizes the biological functions of SCFAs and their role in gut health, as well as nutritional strategies to regulate SCFA production in the poultry gut.

Roles of short-chain fatty acids in kidney diseases.

Objective:In kidney diseases, uncontrolled blood pressure, inflammation, oxidative stress, imbalanced immunity response, and metabolic dysfunction were associated with the progressive deterioration of renal function. Short-chain fatty acids (SCFAs), as a group of metabolites fermented by gut microbiota exerted regulatory effects on kidney diseases through their activation of trans-membrane G protein-coupled receptors and their inhibition of histone acetylation. In this review article, we updated recent research advances that provided an opportunity to explore our understanding in physiology and function of SCFAs in kidney disease.Data sources:We performed a comprehensive search in both PubMed and Embase using “short-chain fatty acids” and “kidney” with no restrictions on publication date.Study selection:After reading through the title and abstract for early screening, the full text of relevant studies was identified and reviewed to summarize the roles of SCFAs in kidney diseases.Results:Though controversial, growing evidence suggested SCFAs appeared to have a complex but yet poorly understood communications with cellular and molecular processes that affected kidney function and responses to injury. From recent studies, SCFAs influenced multiple aspects of renal physiology including inflammation and immunity, fibrosis, blood pressure, and energy metabolism.Conclusions:The roles of intestinal SCFAs in kidney diseases were exciting regions in recent years; however, clinical trials and animal experiments in kidney diseases were still lacked. Thus, more research would be needed to obtain better understanding of SCFAs’ potential effects in kidney diseases.

Gut microbiota-derived short-chain fatty acids and kidney diseases.

Gut microbiota and its metabolites play pivotal roles in host physiology and pathology. Short-chain fatty acids (SCFAs), as a group of metabolites, exert positive regulatory effects on energy metabolism, hormone secretion, immune inflammation, hypertension, and cancer. The functions of SCFAs are related to their activation of transmembrane G protein-coupled receptors and their inhibition of histone acetylation. Though controversial, growing evidence suggests that SCFAs, which regulate inflammation, oxidative stress, and fibrosis, have been involved in kidney disease through the activation of the gut–kidney axis; however, the molecular relationship among gut microbiota–derived metabolites, signaling pathways, and kidney disease remains to be elucidated. This review will provide an overview of the physiology and functions of SCFAs in kidney disease.

B cell-helping functions of gut microbial metabolites.

Commensal microflora profoundly affects the host immune system. It has long been observed that commensal bacteria enhance antibody production in the host by producing antigens for B cell receptors (BCR) and ligands for Toll-like receptors (TLR). We recently reported that the microbial metabolites short-chain fatty acids (SCFAs) regulate the metabolism and gene expression in B cells to promote antibody production (Kim et al. Gut Microbial Metabolites Fuel Host Antibody Responses. Cell Host & Microbe. 2016; 20(2):202-14). The B-cell helping function of SCFAs and its implication in the host immune system are discussed in this article.