Role Of Short-chain Fatty Acids Research Articles

The role of short-chain fatty acid metabolism in the pathogenesis, diagnosis and treatment of cancer.

Short-chain fatty acids (SCFAs), which are saturated fatty acids consisting of six or fewer carbon atoms, have been found to be closely associated with the biological behavior of malignant tumors. This manuscript provides a comprehensive review on the role of SCFAs in regulating cell cycle, apoptosis, tumor angiogenesis, epithelial-mesenchymal transition, protein regulatory pathways, and histone regulation in promoting the development of malignant tumors. Furthermore, we discuss the potential therapeutic strategies targeting SCFAs for treating malignant tumors. This review offers a theoretical foundation for investigating the mechanisms by which SCFAs impact malignant tumors and provides insights into developing novel treatment targets.

Physiologic hypoxia in the intestinal mucosa: a central role for short-chain fatty acids.

The intestinal mucosa is a dynamic surface that facilitates interactions between the host and an outside world that includes trillions of microbes, collectively termed the microbiota. This fine balance is regulated by an energetically demanding physical and biochemical barrier that is formed by the intestinal epithelial cells. In addition, this homeostasis exists at an interface between the anaerobic colonic lumen and a highly oxygenated, vascularized lamina propria. The resultant oxygen gradient within the intestine establishes "physiologic hypoxia" as a central metabolic feature of the mucosa. Although oxygen is vital for energy production to meet cellular metabolism needs, the availability of oxygen has far-reaching influences beyond just energy provision. Recent studies have shown that the intestinal mucosa has purposefully adapted to use differential oxygen levels largely through the presence of short-chain fatty acids (SCFAs), particularly butyrate (BA). Intestinal epithelial cells use butyrate for a multitude of functions that promote mucosal homeostasis. In this review, we explore how the physiologic hypoxia profile interfaces with SCFAs to benefit host mucosal tissues.

Unlocking the power of short-chain fatty acids in ameliorating intestinal mucosal immunity: a new porcine nutritional approach.

Short-chain fatty acids (SCFAs), a subset of organic fatty acids with carbon chains ranging from one to six atoms in length, encompass acetate, propionate, and butyrate. These compounds are the endproducts of dietary fiber fermentation, primarily catalyzed by the glycolysis and pentose phosphate pathways within the gut microbiota. SCFAs act as pivotal energy substrates and signaling molecules in the realm of animal nutrition, exerting a profound influence on the intestinal, immune system, and intestinal barrier functions. Specifically, they contibute to 60-70% of the total energy requirements in ruminants and 10-25% in monogastric animals. SCFAs have demonstrated the capability to effectively modulate intestinal pH, optimize the absorption of mineral elements, and impede pathogen invasion. Moreover, they enhance the expression of proteins associated with intestinal tight junctions and stimulate mucus production, thereby refining intestinal tissue morphology and preserving the integrity of the intestinal structure. Notably, SCFAs also exert anti-inflammatory properties, mitigating inflammation within the intestinal epithelium and strengthening the intestinal barrier's defensive capabilities. The present review endeavors to synthesize recent findings regarding the role of SCFAs as crucial signaling intermediaries between the metabolic activities of gut microbiota and the status of porcine cells. It also provides a comprehensive overview of the current literature on SCFAs' impact on immune responses within the porcine intestinal mucosa.

The role of short-chain fatty acids in the regulation of osteoporosis: new perspectives from gut microbiota to bone health: A review.

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration, resulting in increased fracture risk. With an aging population, osteoporosis imposes a heavy burden worldwide. Current pharmacotherapies such as bisphosphonates can reduce fracture risk but have limitations. Emerging research suggests that gut microbiota regulates bone metabolism through multiple mechanisms. Short-chain fatty acids (SCFAs) produced from microbial fermentation of dietary fiber beneficially impact bone health. Preclinical studies indicate that SCFAs such as butyrate and propionate prevent bone loss in osteoporosis models by inhibiting osteoclastogenesis and immune modulation. Early clinical data also suggest that SCFA supplementation may improve bone turnover markers in postmenopausal women. SCFAs likely act via inhibition of osteoclast differentiation, stimulation of osteoblast activity, regulation of T cells, and other pathways. However, optimal dosing, delivery methods, and long-term safety require further investigation. Modulating the gut-bone axis via supplementation, prebiotics/probiotics, diet, and lifestyle interventions represents an innovative therapeutic approach for osteoporosis. Harnessing the interplay between microbiome, metabolism, immunity, and bone may provide new directions for managing osteoporosis in the future.

Potential role of short-chain fatty acids in the pathogenesis and management of acute lymphocytic leukemia.

Acute lymphocytic leukemia (ALL) is an aggressive hematological malignancy of highly proliferative lymphoblasts. ALL is the most common cancer in children, and is typically treated with combination chemotherapy. The 5-year survival of ALL improved significantly in recent decades with this treatment approach. However, certain age groups (below 2 and over 10 years of age) have much worse prognosis, and over 50% of patients with ALL experience long-term side effects proportional to the dosage of anticancer drugs. Therefore, different treatment strategies are required to improve survival in ALL and to reduce side effects of chemotherapy. Since epigenetic modifications are dominantly reversible, "epidrugs" (drugs targeting epigenetic markers) are considered for feasibility in the treatment of ALL as epigenetic modifications, and acetylation of histones was demonstrated to play a critical role in the pathogenesis of ALL. Histone deacetylases (HDACs) have been shown to be differentially expressed in several hematological malignancies, including ALL. HDAC inhibitors (HDACis) have been shown to express selective toxicity for ALL cells, but they showed limited efficacy and higher than expected toxicity in mouse models or clinical trials in ALL. The aim of this review is to examine the role of the microbiota and microbial metabolites in the mechanisms of HDAC functions, and explore the utilization of the microbiota and microbial metabolites in improving the efficacy of HDACi in ALL. HDAC regulators and natural HDACi are depleted in ALL due to microbiota change leading to a decrease in butyrate and propionate, and HDACi treatment is not effective in ALL due to their short half-life. We propose that HDACi released by the microbiota may be necessary in HDAC regulation and this process is impaired in ALL. Furthermore, the review will also consider the role of restoration of the microbiota or supplementation of natural HDACi in potentially restoring HDAC and HDACi functions.

The Role of Short-Chain Fatty Acids, Particularly Butyrate, in Oncological Immunotherapy with Checkpoint Inhibitors: The Effectiveness of Complementary Treatment with Clostridium butyricum 588.

The discovery of immune checkpoints (CTLA-4, PD-1, and PD-L1) and their impact on the prognosis of oncological diseases have paved the way for the development of revolutionary oncological treatments. These treatments do not combat tumors with drugs "against" cancer cells but rather support and enhance the ability of the immune system to respond directly to tumor growth by attacking the cancer cells with lymphocytes. It has now been widely demonstrated that the presence of an adequate immune response, essentially represented by the number of TILs (tumor-infiltrating lymphocytes) present in the tumor mass decisively influences the response to treatments and the prognosis of the disease. Therefore, immunotherapy is based on and cannot be carried out without the ability to increase the presence of lymphocytic cells at the tumor site, thereby limiting and nullifying certain tumor evasion mechanisms, particularly those expressed by the activity (under positive physiological conditions) of checkpoints that restrain the response against transformed cells. Immunotherapy has been in the experimental phase for decades, and its excellent results have made it a cornerstone of treatments for many oncological pathologies, especially when combined with chemotherapy and radiotherapy. Despite these successes, a significant number of patients (approximately 50%) do not respond to treatment or develop resistance early on. The microbiota, its composition, and our ability to modulate it can have a positive impact on oncological treatments, reducing side effects and increasing sensitivity and effectiveness. Numerous studies published in high-ranking journals confirm that a certain microbial balance, particularly the presence of bacteria capable of producing short-chain fatty acids (SCFAs), especially butyrate, is essential not only for reducing the side effects of chemoradiotherapy treatments but also for a better response to immune treatments and, therefore, a better prognosis. This opens up the possibility that favorable modulation of the microbiota could become an essential complementary treatment to standard oncological therapies. This brief review aims to highlight the key aspects of using precision probiotics, such as Clostridium butyricum, that produce butyrate to improve the response to immune checkpoint treatments and, thus, the prognosis of oncological diseases.

The role of short-chain fatty acids in the formation of non-alcoholic fatty liver disease in children: A review

The role of short-chain fatty acids in the formation of non-alcoholic fatty liver disease in children: A review

The role of short-chain fatty acids in the progression of non-alcoholic fatty liver disease

Introduction. Nowadays, a multifactorial model of the pathogenesis of NAFLD is recognized. It is interesting to study the contribution of changes in the composition of the intestinal microbiota and its metabolites in the development of the disease.Aim. To evaluate the contribution of research into the qualitative composition of the intestinal microbiota in relation to the risk of progression of NAFLD to reduce the loss of health- saving potential of the population.Materials and methods. An open comparative study of 83 mature-aged patients (56.6 years (46–63)) suffering from NAFLD was conducted. The levels of insulin, leptin, its receptor, adiponectin in blood serum, zonulin in feces were studied, and SCFA in feceswas determined. The analysis was carried out depending on the phenotypes of NAFLD: the degree of steatosis (1 – 40 patients, degree 2 – 18 and degree 3 – 25), the presence of NASH (43 patients), the presence of fibrosis (fibrosis was found in 35 patients). The degree of steatosis and fibrosis was assessed using elastometry. The results of the study were analyzed using the Microsoft Excel, STATISTICA 12.0 software package.Results. In patients with NAFLD, the absolute number of all SCFA in the feces was reduced. The anaerobic index was deviated towards sharply negative values (-0,711 (-0,576-(-0,830)). A high level of propionic acid was noted among the patients with fibrosis (p < 0.05). Anaerobic index, relative content of isoC4 + isoC5 + isoC6, relative content of butyric acid had a positive relationship with the St-index (rs = 0.254, rs = 0.269, rs = 0.240, p≤ 0.05). An increase in the relative amount of propionic acid was statistically significantly associated with a decrease of FLI (rs = -0.229, p ≤0.05). A positive correlation was found between the level of insulin and the absolute amount of butyric acid C4 (rs = 0.228, p ≤ 0.05). There was an inverse relationship of the absolute and relative amounts of isoC4+ isoC5 + isoC6 and Iso Cn/Cn with zonulin in the feces (rs = -0.231, p ≤ 0.05, rs = -0.380, p ≤ 0.05 and rs = -0.332, p ≤ 0.05, respectively).Conclusion. There is the anaerobic flora among the patients with NAFLD. Modification of the content of SCFA in feces may affect to the progression of NAFLD. The effect of SCFA on the development and progression of NAFLD may be mediated by the development of insulin and leptin resistance, as well as an integrity violation of the intestinal barrier.

Potential role of short-chain fatty acids in irritable bowel syndrome in overweight and obese individuals

Due to increasing prevalence of functional diseases of the colon in obese patients, the mechanisms by which the intestinal microbiota affects the development of symptoms of irritable bowel syndrome (IBS) in the setting of metabolic activity of adipose tissue should be investigated. The quantitative and qualitative changes in the pool of synthesized short-chain fatty acids, which have a multidirectional impact on the colonic motility is one of the key mechanisms by which the intestinal microbiota affects the occurrence and features of the course of irritable bowel syndrome. But as regards the issue of whether individual short-chain fatty acids have an impact on the severity of abdominal pain and characteristics of colonic motility dysfunction, it remains a subject of discussions. The study of the mechanisms of impact of short-chain fatty acids on the development and progression of obesity deserves special attention. Increased serum and faecal short-chain fatty acid levels in obese patients can either be a result of changes in the intestinal microflora composition associated with special eating habits and lifestyle, or have an independent effect on the development of obesity in individuals due to intestinal microflora composition disorders that have been already developed. Due to special features of the course of irritable bowel syndrome associated with overweight and obesity, studying the intestinal microbiota composition and the short-chain fatty acids produced by it in this cohort of IBS patients is of particular interest. This publication has been prepared to describe and systematize the possible mechanisms of impact of short-chain fatty acids on the development of abdominal pain and impaired colonic motility in IBS patients with overweight and obesity. The literature search was conducted in the databases Embase, PubMed and Google Scholar using the keywords “irritable bowel syndrome”, “obesity”, “short-chain fatty acids”, “gut microbiota”.

Molecular mechanisms and therapeutic possibilities of short-chain fatty acids in posttraumatic stress disorder patients: a mini-review.

This mini-review explores the role of short-chain fatty acids (SCFAs) in posttraumatic stress disorder (PTSD). Highlighting the microbiota-gut-brain axis, this study investigated the bidirectional communication between the gut microbiome and mental health. SCFAs, byproducts of gut microbial fermentation, have been examined for their potential impact on PTSD, with a focus on molecular mechanisms and therapeutic interventions. This review discusses changes in SCFA levels and bacterial profiles in individuals with PTSD, emphasizing the need for further research. Promising outcomes from clinical trials using probiotics and fermented formulations suggest potential avenues for PTSD management. Future directions involve establishing comprehensive human cohorts, integrating multiomics data, and employing advanced computational methods, with the goal of deepening our understanding of the role of SCFAs in PTSD and exploring microbiota-targeted interventions.

#2070 Associations of fecal and plasma levels of SCFAs with gut microbiota and clinical characteristics in non-dialysis renal anemia patients

Abstract Background and Aims Renal anemia is one of the most common complications of Chronic Kidney Disease (CKD). The gut-kidney axis hypothesis has led to numerous studies showing that patients with CKD have a distinct gut microbiota structure compared with controls and that changes in gut microbiota correlate with disease severity and progression. The short-chain fatty acids (SCFAs) are speculated to be pivotal in the gut-kidney crosstalk. However, the role of SCFAs in renal anemia has not been elucidated. This study aimed to explore and compare the fecal and plasma levels of SCFAs in non-dialysis renal anemia patients and healthy controls to reveal the potential interactions among SCFAs, gut microbiota, and clinical features of renal anemia, which may provide new light on further studies. Method A cohort of 30 non-dialysis renal anemia patients and 20 healthy controls were recruited from the First Affiliated Hospital of Zhengzhou University. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. Fecal and plasma concentrations of SCFAs were measured using GC-MS/MS platform. The clinical characteristics of patients with renal anemia and controls were evaluated. Results Renal anemia patients displayed altered microbiota composition compared to healthy subjects. The relative abundance of Enterobacterales, Enterobacteriaceae, Escherichia-Shigella, and Escherichia-coli were higher in patients with renal anemia, and the Lachnospiraceae family decreased in renal anemia patients. In contrast, the relative abundance of Lachnospirales, Lachnospiraceae, and Bacteroides vulgatus was higher in the control group. Patients with renal anemia had higher fecal and plasma concentrations of SCFAs compared to controls. The fecal and plasma concentrations of SCFAs were significantly different not only between the patients with renal anemia and controls but also in the different severity of renal anemia. Moreover, different types of SCFAs are intimately associated with clinical characteristics. The applications of medications may exert effects on the fecal and plasma SCFAs. A positive correlation was obtained between Lachnospirales and the plasma SCFAs. The levels of acetic acid and caproic acid in fecal and the levels of acetic acid, propionic acid, and butyric acid in plasma were all positively correlated with the abundance of Cyanobacteria. Conclusion The gut metabolites SCFAs are tightly linked to the alterations of gut microbiota and clinical characteristics of renal anemia. Further studies are warranted to elucidate the relationships more in-depth.

Development of the CE-C4D method for determination of organic acids in infants faeces using an in-house built instrument

Short-chain fatty acids (SCFAs) are a major group of products produced during colonic bacterial fermentation of nondigestible carbohydrates demonstrating several important functions, e.g. regulating the immune system activity or the lipid metabolism. A detailed profile and concentration characterization of SCFAs in infant faeces is essential for expanding knowledge regarding the role of SCFAs in infant physiology and pathophysiology. This research presents the development and validation of a capillary electrophoresis method with a contactless capacitively coupled conductivity detector (CE-C4D) for the analysis of SCFAs and succinic and lactic acids in infant faeces. The study focused on optimizing the background electrolyte, mainly dynamic capillary coating with polybrene, and utilizing cyclodextrins to achieve efficient separation. Validation parameters, such as linearity (0.993 – 0.998), limits of detection and quantification (LOD: 0.10 – 0.89 μg/mL; LOQ: 0.35 – 2.97 μg/mL), intra- and inter-day precision (1.71 – 5.69 % and 1.11 – 12.5 %, respectively), injection repeatability (0.91 – 5.70 %), trueness (-12.8 – 3.80 %), and matrix effect (78.8 – 108.6 %), were assessed and the method was found suitable for the purpose. The demonstrated method was successfully applied to determine nine organic acids in faecal samples.

Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut-brain-microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother's obesity as potentially environmental factors of ASD. The purpose of this review is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.

The role of short-chain fatty acids in central nervous system diseases: A bibliometric and visualized analysis with future directions

BackgroundShort-chain fatty acids (SCFAs) are thought to play a key role in the microbe-gut-brain axis and involve in the pathogenesis of a variety of neurological diseases. This study aimed to identify research hotspots and evolution trends in SCFAs in central nervous diseases (CNS) and examine current research trends. MethodsThe bibliometric analysis was performed using CiteSpace, and the results were visualized via network maps. ResultsFrom 2002 to 2022, 480 publications in the database met the criteria. On the country level, China produced the highest number of publications, while the United States had the highest centrality. On the institutional level, University College Cork contributed to the most publications, and John F. Cryan from this university was the key researcher with considerable academic influence. The article, the role of short-chain fatty acids in microbiota-gut-brain, written by Boushra Dalile et al., in 2019 was the most cited article. Furthermore, the journal Nutrients had the maximum number of publications, while Plos One was the most cited journal. “Gut microbiome”, “SCFAs”, and “central nervous system” were the three most frequent keywords. Among them, SCFAs had the highest centrality. “Animal model” was the keyword with the highest burst strength, with the latest burst keywords being “social behavior”, “pathogenesis”, and “insulin sensitive”. In addition, the research topics on SCFAs in CNS diseases from 2002 to 2022 mainly focused on following aspects: SCFAs plays a key role in microbe-gut-brain crosstalk; The classification and definition of SCFAs in the field of CNS; Several CNS diseases that are closely related to SCFAs research; Mechanism and translational studies of SCFAs in the CNS diseases. And the hotspots over the past 5 years have gradually increased the attention to the therapeutic potential of SCFAs in the CNS diseases. ConclusionThe research of SCFAs in CNS diseases is attracting growing attention. However, there is a lack of cooperation between countries and institutions, and additional measures are required to promote cooperation. The current evidence for an association between SCFAs and CNS diseases is preliminary and more work is needed to pinpoint the precise mechanism. Moreover, large-scale clinical trials are needed in the future to define the therapeutic potential of SCFAs in CNS diseases.

Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD.

Group 2 innate lymphoid cells (ILC2) strongly modulate COPD pathogenesis. However, the significance of microbiota in ILC2s remains unelucidated. Herein, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) in regulating ILC2-associated airway inflammation and explores its associated mechanism in COPD. In particular, we assessed the SCFA-mediated regulation of survival, proliferation, and cytokine production in lung sorted ILC2s. To elucidate butyrate action in ILC2-driven inflammatory response in COPD models, we administered butyrate to BALB/c mice via drinking water. We revealed that SCFAs, especially butyrate, derived from dietary fiber fermentation by gut microbiota inhibited pulmonary ILC2 functions and suppressed both IL-13 and IL-5 synthesis by murine ILC2s. Using in vivo and in vitro experimentation, we validated that butyrate significantly ameliorated ILC2-induced inflammation. We further demonstrated that butyrate suppressed ILC2 proliferation and GATA3 expression. Additionally, butyrate potentially utilized histone deacetylase (HDAC) inhibition to enhance NFIL3 promoter acetylation, thereby augmenting its expression, which eventually inhibited cytokine production in ILC2s. Taken together, the aforementioned evidences demonstrated a previously unrecognized role of microbial-derived SCFAs on pulmonary ILC2s in COPD. Moreover, our evidences suggest that metabolomics and gut microbiota modulation may prevent lung inflammation of COPD.

Possible roles of short-chain fatty acids produced by oral bacteria in the development of alveolar osteitis.

Alveolar osteitis (dry sockets) is a painful condition characterized by a limited immune response. It is typically caused by the removal of blood clots from extracted tooth sockets, which leads to the fermentation of trapped food remnants by oral bacteria in the cavities, producing high concentrations of short-chain fatty acids (SCFAs). This study examined the effects of SCFAs on immunity and bone metabolism. Mouse macrophage Raw264.7 cells were treated with oral bacteria supernatants or SCFA mixtures, and inducible nitric oxide synthase (iNOS) levels were determined by western blot. The same cells were treated with SCFA mixtures in the presence of receptor activator of nuclear factor-kappa B ligand (RANKL), and osteoclast-like cells were counted. MC3T3-E1 cells were treated with SCFA mixtures and stained with alizarin red S. Raw264.7 cells treated with oral bacterial culture supernatants of Porphyromonas gingivalis and Fusobacterium nucleatum inhibited lipopolysaccharide (LPS)-induced iNOS production, likely due to SCFA content. SCFA mixtures mimicking these supernatants inhibited the number of RANKL-induced tartrate-resistant acid phosphatase (TRAP)-positive cells and MC3T3-E1 cell mineralization. These data suggest that SCFAs produced by P. gingivalis and F. nucleatum may reduce the inflammatory response and mildly induce mineralization of the alveolar walls. These results may contribute to the understanding of alveolar osteitis.

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.

The Role of Short-Chain Fatty Acids and Altered Microbiota Composition in Autism Spectrum Disorder: A Comprehensive Literature Review.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in communication and social interactions, restrictive and repetitive behavior, and a wide range of cognitive impediments. The prevalence of ASD tripled in the last 20 years and now affects 1 in 44 children. Although ASD's etiology is not yet elucidated, a growing body of evidence shows that it stems from a complex interplay of genetic and environmental factors. In recent years, there has been increased focus on the role of gut microbiota and their metabolites, as studies show that ASD patients show a significant shift in their gut composition, characterized by an increase in specific bacteria and elevated levels of short-chain fatty acids (SCFAs), especially propionic acid (PPA). This review aims to provide an overview of the role of microbiota and SCFAs in the human body, as well as possible implications of microbiota shift. Also, it highlights current studies aiming to compare the composition of the gut microbiome of ASD-afflicted patients with neurotypical control. Finally, it highlights studies with rodents where ASD-like symptoms or molecular hallmarks of ASD are evoked, via the grafting of microbes obtained from ASD subjects or direct exposure to PPA.

A gutsy performance: the potential for supplementation of short-chain fatty acids to benefit athletic health, exercise performance, and recovery.

The gut microbiome is known to play an important role in the day-to-day physiology and health of the human host. It is, therefore, not surprising that there is interest surrounding the gut microbiome and its potential to benefit athletic health and performance. This has, in part, been driven by the consideration that gut bacterial by-products (i.e. metabolic waste) could be harnessed by the host and utilised for a beneficial outcome. The concept of harnessing bacterial metabolites as beneficial health modulators has developed the theory of leveraging short-chain fatty acids (SCFAs) as novel supplements for enhancing athletic performance. This review discusses the current literature investigating SCFA administration in cellular, animal, and human models, with the aim of linking the demonstrated physiological/biochemical mechanisms to potential exercise/athletic benefit. In addition, practical implications and factors relating to SCFA-supplementation in athletic populations are considered. The literature demonstrates a tangible rationale that SCFAs can have a positive impact on human physiology to afford benefits to the athletic population. These advantages include the capacity to improve respiratory immunity to combat elevated levels/severity of upper respiratory tract infections often reported in athletes; the blunting of pro-inflammatory and pro-fibrotic pathways to aid in exercise recovery; and the role of SCFAs as usable energy sources and metabolism modulators to fuel exercise and improve performance and/or endurance capacity. However, there is currently minimal research completed in human participants and thus further investigations into the direct benefit of SCFAs in exercise performance and/or recovery-based studies are required.

The roles of short-chain fatty acids derived from colonic bacteria fermentation of non-digestible carbohydrates and exogenous forms in ameliorating intestinal mucosal immunity of young ruminants.

Short-chain fatty acids (SCFA) are a class of organic fatty acids that consist of 1 to 6 carbons in length. They are primary end-products which arise from non-digestible carbohydrates (NDC) fermentation of colonic bacteria. They are the fundamental energy sources for post-weaning ruminants. SCFA represent the major carbon flux of diet through the gut microbiota to the host. They also play a vital role in regulating cell expansion and gene expression of the gastrointestinal tract (GIT). Recently, remarkable progresses have been made in understanding the immunomodulatory effects of SCFA and their interactions with the host. The processes involved in this study encompassed inflammasome activation, proliferation of lymphocytes, and maturation of intestinal mucosal immunity maturation. It is important to note that the establishment and maturation of intestinal mucosal immune system are intricately connected to the barrier function of intestinal epithelial cells (IEC) and the homeostasis of gut microbiota. Thus, insights into the role of SCFA in enteric mucosal immunoreaction of calves will enhance our understanding of their various regulatory functions. This review aims to analyze recent evidence on the role of SCFA as essential signaling molecules between gut microbiota and animal health. Additionally, we provide a summary of current literature on SCFA in intestinal mucosal immune responses of dairy calves.