Association between short-chain fatty acid intake and development of muscle strength loss among community-dwelling older Japanese adults.

BACKGROUND: Short-chain fatty acids (SCFAs) have been suggested to be associated with skeletal muscle mass maintenance. However, the role of dietary SCFAs in preserving muscle strength in the older population remains unclear. OBJECTIVES: To clarify the longitudinal association between the dietary intake of SCFAs and the development of low muscle strength in older community dwellers. METHODS: Data were obtained from the National Institute for Longevity Sciences-Longitudinal Study of Aging cohort. The participants included 441 men and 382 women who participated in the baseline survey (the fifth wave, between 2006 and 2008) and at least one follow-up examination (sixth to ninth waves, between 2008 and 2022) and were ≥60 years old and did not have low muscle strength (defined as a grip strength of <28 kg for men and <18 kg for women) at baseline. Baseline nutrient intakes were assessed with a 3-day dietary record. A generalized estimating equation was employed to estimate the odds ratio (OR) and 95 % confidence intervals (CIs) for low muscle strength per 1 standard deviation (SD) increase in the intake of SCFAs and other nutrients at baseline (adjusted for sex, age, follow-up time, baseline grip strength, physical activity, smoking, family income, education, and disease histories). RESULTS: The mean (SD) follow-up time and number were 7.8 (3.2) years and 3.2 (1.0) times, respectively. Approximately 8.1 % of the participants exhibited muscle strength loss in at least one follow-up assessment. The multivariate-adjusted OR (95 % CIs) was 0.77 (0.63-0.93) for each 1-SD increase in SCFA intake (268 mg/day), and the ORs for the highest through the lowest tertiles of SCFA intake were 1.00 (reference), 1.44 (0.95-2.17), and 1.83 (1.20-2.78), respectively (trend p = 0.005). The results remained significant after multivariate adjusting for energy or fat intake. CONCLUSION: Dietary intake of SCFAs may prevent muscle strength decline in community-dwelling older adults.

Impact of short-chain fatty acid supplementation on gut inflammation and microbiota composition in a murine colitis model.

Short-chain fatty acids (SCFAs) play a pivotal role in maintaining intestinal homeostasis. We aimed to investigate the effects of SCFA supplementation on gut inflammation and microbiota composition in a murine colitis model. Mice were fed with sodium butyrate or a mixture of SCFAs in the drinking water for 2 weeks, followed by 2% dextran sulfate sodium (DSS) for 7 d. After euthanasia, mouse colons were extracted to examine histological findings. Flow cytometry of the mouse colon tissues was performed to assess T cell differentiation. Changes in gut microbiota were assessed by high-throughput sequencing of the mouse feces. There were no significant differences in weight change, colonic length, or histologic inflammation score between the DSS, butyrate, and SCFA mix groups. However, flow cytometry revealed that both the expression of CD4+Foxp3+ regulatory T cells and of IL-17-producing T cells were increased in the butyrate and SCFA mix groups. Microbial compositions of the butyrate and SCFA mix groups were significantly different from those of the control and DSS groups in principal coordinate analysis. Relative abundances of the phyla Verrucomicrobia and Proteobacteria, species Akkermansia muciniphila and Escherichia fergusonii were increased in the butyrate and SCFA mix groups. Genera Roseburia and Lactobacillus showed a negative correlation with the degree of colitis, whereas genera Escherichia and Mucispirillum showed a positive correlation. SCFA supplementation did not result in a significant reduction in colon inflammation, but it promoted both regulatory T cell and IL-17-producing T cell expression, and increased both protective and aggressive gut microbiota.

Alteration of the gut microbiota following SARS-CoV-2 infection correlates with disease severity in hamsters.

Mounting evidence suggests that the gut-to-lung axis is critical during respiratory viral infections. We herein hypothesized that disruption of gut homeostasis during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may associate with early disease outcomes. To address this question, we took advantage of the Syrian hamster model. Our data confirmed that this model recapitulates some hallmark features of the human disease in the lungs. We further showed that SARS-CoV-2 infection associated with mild intestinal inflammation, relative alteration in intestinal barrier property and liver inflammation and altered lipid metabolism. These changes occurred concomitantly with an alteration of the gut microbiota composition over the course of infection, notably characterized by a higher relative abundance of deleterious bacterial taxa such as Enterobacteriaceae and Desulfovibrionaceae. Conversely, several members of the Ruminococcaceae and Lachnospiraceae families, including bacteria known to produce the fermentative products short-chain fatty acids (SCFAs), had a reduced relative proportion compared to non-infected controls. Accordingly, infection led to a transient decrease in systemic SCFA amounts. SCFA supplementation during infection had no effect on clinical and inflammatory parameters. Lastly, a strong correlation between some gut microbiota taxa and clinical and inflammation indices of SARS-CoV-2 infection severity was evidenced. Collectively, alteration of the gut microbiota correlates with disease severity in hamsters making this experimental model valuable for the design of interventional, gut microbiota-targeted, approaches for the control of COVID-19.Abbreviations: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; COVID-19, coronavirus disease 2019; SCFAs, short-chain fatty acids; dpi, day post-infection; RT-PCR, reverse transcription polymerase chain reaction; IL, interleukin. ACE2, angiotensin converting enzyme 2; TMPRSS2, transmembrane serine protease 2.

SCFAs improve disease resistance via modulate gut microbiota, enhance immune response and increase antioxidative capacity in the host.

To evaluate the effects of dietary short chain fatty acids (SCFAs) on the intestinal health and innate immunity in crucian carp, a six-week feeding trial was carried out with following treatments: basal diet (BD), basal diet supplementation with 1% sodium acetate (BDSA), basal diet supplementation with 1% sodium propionate (BDSP) and basal diet supplementation with 1% sodium butyrate (BDSB). The results showed dietary BDSA, BDSP and BDSB could protect the host against oxidative stress by improving the activity of certain antioxidative enzymes (T-SOD, GSH-Px and CAT). Additionally, dietary SCFAs could enhance mucosal and humoral immune responses by improving certain innate immune parameters in serum and skin mucus productions (IgM, ACH50 and T-SOD). Furthermore, dietary BDSA and BDSP could up-regulate the expression of immune related genes (TNF-α, TGF-ß and IL-8) and tight junction protein genes (occludin and ZO-1). Dietary BDSB could also elevate the expression of IL-8, TGF-ß, ZO-1 and Occludin in the midgut. Although dietary differences of SCFAs didn't alter the α-diversity of the intestinal flora, they altered the core microbiota. Finally, the challenge trial showed that dietary basal diet supplementation with SCFAs could protect zebrafish against Aeromonas hydrophila. These results suggest that dietary SCFAs could improve innate immunity, modulate gut microbiota and increase disease resistance in the host, which indicated the potential of SCFAs as immunostimulants in aquaculture.

SCFA Treatment Alleviates Pathological Signs of Migraine and Related Intestinal Alterations in a Mouse Model of NTG-Induced Migraine.

BACKGROUND: There is a growing realization that the gut-brain axis signaling is critical for maintaining the health and homeostasis of the Central Nervous System (CNS) and the intestinal environment. The role of Short-Chain Fatty Acids (SCFAs), such as Sodium Propionate (SP) and Sodium Butyrate (SB), has been reported to counteract inflammation activation in the central and Enteric Nervous System (ENS). METHODS: In this study, we evaluated the role of the SCFAs in regulating the pathophysiology of migraine and correlated dysregulations in the gut environment in a mouse model of Nitroglycerine (NTG)-induced migraine. RESULTS: We showed that, following behavioral tests evaluating pain and photophobia, the SP and SB treatments attenuated pain attacks provoked by NTG. Moreover, treatments with both SCFAs reduced histological damage in the trigeminal nerve nucleus and decreased the expression of proinflammatory mediators. Ileum evaluation following NTG injection reported that SCFA treatments importantly restored intestinal mucosa alterations, as well as the release of neurotransmitters in the ENS. CONCLUSIONS: Taken together, these results provide evidence that SCFAs exert powerful effects, preventing inflammation through the gut-brain axis, suggesting a new insight into the potential application of SCFAs as novel supportive therapies for migraine and correlated intestinal alterations.

The Athlete and Gut Microbiome: Short-chain Fatty Acids as Potential Ergogenic Aids for Exercise and Training.

Short-chain fatty acids (SCFAs) are metabolites produced in the gut via microbial fermentation of dietary fibers referred to as microbiota-accessible carbohydrates (MACs). Acetate, propionate, and butyrate have been observed to regulate host dietary nutrient metabolism, energy balance, and local and systemic immune functions. In vitro and in vivo experiments have shown links between the presence of bacteria-derived SCFAs and host health through the blunting of inflammatory processes, as well as purported protection from the development of illness associated with respiratory infections. This bank of evidence suggests that SCFAs could be beneficial to enhance the athlete's immunity, as well as act to improve exercise recovery via anti-inflammatory activity and to provide additional energy substrates for exercise performance. However, the mechanistic basis and applied evidence for these relationships in humans have yet to be fully established. In this narrative review, we explore the existing knowledge of SCFA synthesis and the functional importance of the gut microbiome composition to induce SCFA production. Further, changes in gut microbiota associated with exercise and various dietary MACs are described. Finally, we provide suggestions for future research and practical applications, including how these metabolites could be manipulated through dietary fiber intake to optimize immunity and energy metabolism.

Short Chain Fatty Acid Acetate Increases TNFα-Induced MCP-1 Production in Monocytic Cells via ACSL1/MAPK/NF-κB Axis.

Short-chain fatty acid (SCFA) acetate, a byproduct of dietary fiber metabolism by gut bacteria, has multiple immunomodulatory functions. The anti-inflammatory role of acetate is well documented; however, its effect on monocyte chemoattractant protein-1 (MCP-1) production is unknown. Similarly, the comparative effect of SCFA on MCP-1 expression in monocytes and macrophages remains unclear. We investigated whether acetate modulates TNFα-mediated MCP-1/CCL2 production in monocytes/macrophages and, if so, by which mechanism(s). Monocytic cells were exposed to acetate with/without TNFα for 24 h, and MCP-1 expression was measured. Monocytes treated with acetate in combination with TNFα resulted in significantly greater MCP-1 production compared to TNFα treatment alone, indicating a synergistic effect. On the contrary, treatment with acetate in combination with TNFα suppressed MCP-1 production in macrophages. The synergistic upregulation of MCP-1 was mediated through the activation of long-chain fatty acyl-CoA synthetase 1 (ACSL1). However, the inhibition of other bioactive lipid enzymes [carnitine palmitoyltransferase I (CPT I) or serine palmitoyltransferase (SPT)] did not affect this synergy. Moreover, MCP-1 expression was significantly reduced by the inhibition of p38 MAPK, ERK1/2, and NF-κB signaling. The inhibition of ACSL1 attenuated the acetate/TNFα-mediated phosphorylation of p38 MAPK, ERK1/2, and NF-κB. Increased NF-κB/AP-1 activity, resulting from acetate/TNFα co-stimulation, was decreased by ACSL1 inhibition. In conclusion, this study demonstrates the proinflammatory effects of acetate on TNF-α-mediated MCP-1 production via the ACSL1/MAPK/NF-κB axis in monocytic cells, while a paradoxical effect was observed in THP-1-derived macrophages.

Improvement of colonic healing and surgical recovery with perioperative supplementation of inulin and galacto-oligosaccharides.

BACKGROUND AND AIMS: Anastomotic leak (AL) is a major complication in colorectal surgery. Recent evidence suggests that the gut microbiota may affect healing and may cause or prevent AL. Butyrate is a beneficial short-chain fatty acid (SCFA) that is produced as a result of bacterial fermentation of dietary oligosaccharides and has been described as beneficial in the maintenance of colonic health. To assess the impact of oligosaccharides on colonic anastomotic healing in mice, we propose to modulate the microbiota with oligosaccharides to increase butyrate production via enhancement of butyrate-producing bacteria and, consequently, improve anastomotic healing in mice. METHODS: Animal experiments were conducted in mice that were subjected to diets supplemented with inulin, galacto-oligosaccharides (GOS) or cellulose, as a control, for two weeks before undergoing a surgical colonic anastomosis. Macroscopic and histological assessment of the anastomosis was performed. Extent of epithelial proliferation was assessed by Ki-67 immunohistochemistry. Gelatin zymography was used to evaluate the extent of matrix metalloproteinase (MMP) hydrolytic activity. RESULTS: Inulin and GOS diets were associated with increased butyrate production and better anastomotic healing. Histological analysis revealed an enhanced mucosal continuity, and this was associated with an increased re-epithelialization of the wound as determined by increased epithelial proliferation. Collagen concentration in peri-anastomotic tissue was higher with inulin and GOS diets and MMP activity, a marker of collagen degradation, was lower with both oligosaccharides. Inulin and GOS diets were further associated with lower bacterial translocation. CONCLUSIONS: Dietary supplementation with inulin and GOS may improve anastomotic healing and reinforce the gut barrier in mice.

Centrally administered butyrate improves gut barrier function, visceral sensation and septic lethality in rats.

Short chain fatty acids readily crosses the gut-blood and blood-brain barrier and acts centrally to influence neuronal signaling. We hypothesized that butyrate, a short-chain fatty acid produced by bacterial fermentation, in the central nervous system may play a role in the regulation of intestinal functions. Colonic permeability and visceral sensation was evaluated in rats. Septic lethality was evaluated in a sepsis model induced by subcutaneous administration of both lipopolysaccharide and colchicine. Intracisternal butyrate dose-dependently improved colonic hyperpermeability and visceral nociception. In contrast, subcutaneous injection of butyrate failed to change it. Intracisternal orexin 1 receptor antagonist or surgical vagotomy blocked the central butyrate-induced improvement of colonic hyperpermeability. The improvement of intestinal hyperpermeability by central butyrate or intracisternal orexin-A was blocked by cannabinoid 1 or 2 receptor antagonist. Intracisternal butyrate significantly improved survival period in septic rats. These results suggest that butyrate acts in the central nervous system to improve gut permeability and visceral nociception through cannabinoid signaling. Endogenous orexin in the brain may mediate the reduction of intestinal hyperpermeability by central butyrate through the vagus nerve. We would suggest that improvement of leaky gut by central butyrate may induce visceral antinociception and protection from septic lethality.

Selected Clostridia Strains from The Human Microbiota and their Metabolite, Butyrate, Improve Experimental Autoimmune Encephalomyelitis.

Gut microbiome studies in multiple sclerosis (MS) patients are unravelling some consistent but modest patterns of gut dysbiosis. Among these, a significant decrease of Clostridia cluster IV and XIVa has been reported. In the present study, we investigated the therapeutic effect of a previously selected mixture of human gut-derived 17 Clostridia strains, which belong to Clostridia clusters IV, XIVa, and XVIII, on the clinical outcome of experimental autoimmune encephalomyelitis (EAE). The observed clinical improvement was related to lower demyelination and astrocyte reactivity as well as a tendency to lower microglia reactivity/infiltrating macrophages and axonal damage in the central nervous system (CNS), and to an enhanced immunoregulatory response of regulatory T cells in the periphery. Transcriptome studies also highlighted increased antiinflammatory responses related to interferon beta in the periphery and lower immune responses in the CNS. Since Clostridia-treated mice were found to present higher levels of the immunomodulatory short-chain fatty acid (SCFA) butyrate in the serum, we studied if this clinical effect could be reproduced by butyrate administration alone. Further EAE experiments proved its preventive but slight therapeutic impact on CNS autoimmunity. Thus, this smaller therapeutic effect highlighted that the Clostridia-induced clinical effect was not exclusively related to the SCFA and could not be reproduced by butyrate administration alone. Although it is still unknown if these Clostridia strains will have the same effect on MS patients, gut dysbiosis in MS patients could be partially rebalanced by these commensal bacteria and their immunoregulatory properties could have a beneficial effect on MS clinical course.

Intraperitoneal Administration of Short-Chain Fatty Acids Improves Lipid Metabolism of Long-Evans Rats in a Sex-Specific Manner.

Short-chain fatty acids (SCFAs) are microbial metabolites, mainly generated by the action of gut microbiota on dietary fibers. Acetate, propionate, and butyrate are the three main SCFAs produced typically in a 60:20:20 molar ratio in the colon. Acetate, propionate, and butyrate, when given individually as supplements, have shown a protective role in obesity and hyperglycemia; however, the sex-specific effects of a mixture of SCFAs, when given in 60:20:20 ratio, on the regulation of lipid metabolism and lipid profile are not known. Male and female Long-Evans rats were given a mixture of SCFAs (acetate, propionate, and butyrate; molar ratio 60:20:20) each day for seven days intraperitoneally; plasma and hepatic lipids, gene expression, and lipidomics profile were analyzed. SCFAs significantly decreased plasma and hepatic triglycerides and cholesterol in males, whereas the fatty acyl composition of cholesteryl esters, triglycerides, and phospholipids was modulated in females. SCFAs decreased the mRNA expression of hepatic acetyl-CoA carboxylase-1 in both males and females. Our findings demonstrate for the first time that SCFAs (60:20:20) improved plasma and hepatic lipid levels and fatty acyl composition in a manner that may provide cardio-protective and anti-inflammatory effects in both sexes, via independent mechanisms.

Short-chain free-fatty acid G protein-coupled receptors in colon cancer.

The dietary role of macronutrients and their metabolites in cancer has been evident for many decades. Dietary ingestion of fat, carbohydrates, protein, and fiber, as well as probiotics that influence gut microbiota, have all been linked to gastrointestinal (GI) tract health and disease, particularly in the colon, where it has long been known that fat and fiber can regulate inflammation and carcinogenesis. Short-chained fatty acids (SCFA), including acetate, propionate, and butyrate, which are biosynthesized by microbiota-mediated metabolism of dietary fiber, have previously been shown to play important roles in colorectal health, including decreasing inflammation and oxidative stress. Since the 1980s, a growing number of studies have also demonstrated a link between SCFA and colon epithelial cell carcinogenesis and prevention of colorectal cancers (CRC). While the effects of SCFA have historically been associated with their intracellular metabolism and function, the discovery of a family of G protein-coupled free-fatty acid receptors in the early 2000s suggests that many effects of SCFA are cell-surface receptor mediated. Indeed, the SCFA GPCRs FFA2 (previously termed GPR43), FFA3 (previously termed GPR41), and GPR109A are now well established to be expressed within the GI tract, where they modulate a variety of functions in response to luminal SCFA. While the role of SCFA in cancers, including CRC, has been reviewed in detail elsewhere, the goal of this report is to provide a review on the current body of evidence in regard to the effects of SCFA on FFA2, FFA3, and GPR109A in colon cancers.

Short-chain fatty acids contribute to neuropathic pain via regulating microglia activation and polarization.

Microglia activation and subsequent pro-inflammatory responses play a key role in the development of neuropathic pain. The process of microglia polarization towards pro-inflammatory phenotype often occurs during neuroinflammation. Recent studies have demonstrated an active role for the gut microbiota in promoting microglial full maturation and inflammatory capabilities via the production of Short-Chain Fatty Acids (SCFAs). However, it remains unclear whether SCFAs is involved in pro-inflammatory/anti-inflammatory phenotypes microglia polarization in the neuropathic pain. In the present study, chronic constriction injury (CCI) was used to induce neuropathic pain in mice, the mechanical withdrawal threshold, thermal hyperalgesia were accomplished. The levels of microglia markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation 11b (CD11b), pro-inflammatory phenotype markers including CD68, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and anti-inflammatory phenotype markers including CD206, IL-4 in the hippocampus and spinal cord were determined on day 21 after CCI. The results showed that CCI produced mechanical allodynia and thermal hyperalgesia, and also increased the expressions of microglia markers (Iba1, CD11b) and pro-inflammatory phenotype markers (CD68, IL-1ß, and TNF-α), but not anti-inflammatory phenotype marker (CD206, IL-4) in the hippocampus and spinal cord, accompanied by increased SCFAs in the gut. Notably, antibiotic administration reversed these abnormalities, and its effects was also bloked by SCFAs administration. In conclusion, data from our study suggest that CCI can lead to mechanical and thermal hyperalgesia, while SCFAs play a key role in the pathogenesis of neuropathic pain by regulating microglial activation and subsequent pro-inflammatory phenotype polarization. Antibiotic administration may be a new treatment for neuropathic pain by reducing the production of SCFAs and further inhibiting the process of microglia polarization.

Acetate, a Short-Chain Fatty Acid, Acutely Lowers Heart Rate and Cardiac Contractility Along with Blood Pressure.

Short-chain fatty acids (SCFAs) are metabolites produced almost exclusively by the gut microbiota and are an essential mechanism by which gut microbes influence host physiology. Given that SCFAs induce vasodilation, we hypothesized that they might have additional cardiovascular effects. In this study, novel mechanisms of SCFA action were uncovered by examining the acute effects of SCFAs on cardiovascular physiology in vivo and ex vivo. Acute delivery of SCFAs in conscious radiotelemetry-implanted mice results in a simultaneous decrease in both mean arterial pressure and heart rate (HR). Inhibition of sympathetic tone by the selective ß-1 adrenergic receptor antagonist atenolol blocks the acute drop in HR seen with acetate administration, yet the decrease in mean arterial pressure persists. Treatment with tyramine, an indirect sympathomimetic, also blocks the acetate-induced acute drop in HR. Langendorff preparations show that acetate lowers HR only after long-term exposure and at a smaller magnitude than seen in vivo. Pressure-volume loops after acetate injection show a decrease in load-independent measures of cardiac contractility. Isolated trabecular muscle preparations also show a reduction in force generation upon SCFA treatment, though only at supraphysiological concentrations. These experiments demonstrate a direct cardiac component of the SCFA cardiovascular response. These data show that acetate affects blood pressure and cardiac function through parallel mechanisms and establish a role for SCFAs in modulating sympathetic tone and cardiac contractility, further advancing our understanding of the role of SCFAs in blood pressure regulation. SIGNIFICANCE STATEMENT: Acetate, a short-chain fatty acid, acutely lowers heart rate (HR) as well as mean arterial pressure in vivo in radiotelemetry-implanted mice. Acetate is acting in a sympatholytic manner on HR and exerts negative inotropic effects in vivo. This work has implications for potential short-chain fatty acid therapeutics as well as gut dysbiosis-related disease states.

Dietary SCFAs Immunotherapy: Reshaping the Gut Microbiota in Diabetes.

Diet-microbiota related inflammatory conditions such as obesity, autoimmune type 1 diabetes (T1D), type 2 diabetes (T2D), cardiovascular disease (CVD) and gut infections have become a stigma in Western societies and developing nations. This book chapter examines the most relevant pre-clinical and clinical studies about diet-gut microbiota approaches as an alternative therapy for diabetes. We also discuss what we and others have extensively investigated- the power of dietary short-chain fatty acids (SCFAs) technology that naturally targets the gut microbiota as an alternative method to prevent and treat diabetes and its related complications.

Supplementing the Diet with Sodium Propionate Suppresses the Severity of Viral Immuno-inflammatory Lesions.

This report evaluates a dietary manipulation approach to suppress the severity of ocular infections caused by herpes simplex virus infection. The virus causes chronic damage to the cornea that results from a T-cell-orchestrated inflammatory reaction to the infection. Lesion severity can be limited if cells with regulatory activity predominate over proinflammatory T cells and nonlymphoid inflammatory cells. In this report, we show that this outcome can be achieved by including the short-chain fatty acid (SCFA) salt sodium propionate (SP) in the drinking water. Animals given the SP supplement developed significantly fewer ocular lesions than those receiving no supplement. Corneas and lymphoid organs contained fewer CD4 Th1 and Th17 T cells, neutrophils, and macrophages than those of controls, but a higher frequency of regulatory T cells (Treg) was present. The inclusion of SP in cultures to induce CD4 T cell subsets in vitro reduced the magnitude of Th1 and Th17 responses but expanded Treg induction. Dietary manipulation was an effective approach to limit the severity of viral immuno-inflammatory lesions and may be worth exploring as a means to reduce the impact of herpetic lesions in humans.IMPORTANCE Herpetic lesions are a significant problem, and they are difficult to control with therapeutics. Our studies show that the severity of herpetic lesions in a mouse model can be diminished by changing the diet to include increased levels of SCFA, which act to inhibit the involvement of inflammatory T cells. We suggest that changing the diet to include higher levels of SCFA might be a useful approach to reducing the impact of recurrent herpetic lesions in humans.

The gut microbiome as a target for adjuvant therapy in obstructive sleep apnea.

Introduction: Gut dysbiosis is assumed to play a role in obstructive sleep apnea (OSA)-associated morbidities. Pre- and probiotics, short chain fatty acids (SCFA) and fecal matter transplantation (FMT) may offer potential as novel therapeutic strategies that target this gut dysbiosis. As more mechanisms of OSA-induced dysbiosis are being elucidated, these novel approaches are being tested in preclinical and clinical development. Areas covered: We examined the evidence linking OSA to gut dysbiosis and discuss the effects of pre- and probiotics on associated cardiometabolic, neurobehavioral and gastrointestinal disorders. The therapeutic potential of SCFA and FMT are also discussed. We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central between 2000 - 2020. Expert opinion: To date, there are no clinical trials and only limited evidence from animal studies describing the beneficial effects of pre- and probiotic supplementation on OSA-mediated dysbiosis. Thus, more work is necessary to assess whether prebiotics, probiotics and SCFA are promising future novel strategies for targeting OSA-mediated dysbiosis.

Sucrose Matters. The Need to Make Groups Truly Comparable When Assessing Changes Associated with Insulin Sensitivity. Comment on "Consumption of Cooked Black Beans Stimulates a Cluster of Some Clostridia Class Bacteria Decreasing Inflammatory Response and Improving Insulin Sensitivity." Nutrients 2020, 12(4), 1182.

The recent paper by Sanchez-Tapia et al [...].

Organic acid blend supplementation increases butyrate and acetate production in Salmonella enterica serovar Typhimurium challenged broilers.

The burden of enteric pathogens in poultry is growing after the ban of antibiotic use in animal production. Organic acids gained attention as a possible alternative to antibiotics due to their antimicrobial activities, improved nutrient metabolism and performance. The current study was conducted to evaluate the effectiveness of organic acid blend on broilers cecal microbiota, histomorphometric measurements, and short-chain fatty acid production in Salmonella enterica serovar Typhimurium challenge model. Birds were divided into four treatments, including a negative control, positive control challenged with S. Typhimurium, group supplemented with an organic acid blend, and birds supplemented with organic acid blend and Salmonella challenged. Results illustrate significant differences in feed conversion ratios and production efficiency factor between treatment groups, however, the influence of organic acid supplement was marginal. Organic acid blend significantly increased cecal acetic and butyric acids concentrations when compared to unsupplemented groups and resulted in minor alterations of intestinal bacterial communities.

Anti-neuroinflammatory Effect of Short-Chain Fatty Acid Acetate against Alzheimer's Disease via Upregulating GPR41 and Inhibiting ERK/JNK/NF-κB.

Alzheimer's disease (AD) is a high-incidence neurodegenerative disease in the elderly. Acetate (Ace) is a short-chain fatty acid (SCFA) with neuroprotective activity. The purpose of this study was to investigate the effects and its possible mechanisms of SCFA Ace on AD. A male APP/PS1 transgenic mouse was given intragastric administration Ace for 4 weeks. Cognitive function and microglia activation in mice were assessed. Furthermore, Ace pretreated amyloid-ß (Aß)-induced BV2 microglia, and the levels of CD11b, COX-2, and G-protein-coupled receptor 41 (GPR41) and phosphorylation of ERK, JNK, and NF-κB p65 were determined. Our results revealed that Ace significantly attenuated the cognitive impairment and decreased the CD11b level in the APP/PS1 mice. Moreover, Ace inhibited the phosphorylation of NF-κB p65, ERK, and JNK and decreased the levels of COX-2 and interleukin 1ß in the Aß-stimulated BV2 microglia. Finally, Ace increased the GPR41 level in the Aß-stimulated BV2 cells. The finding indicated that Ace exerted antineuroinflammatory effects via the upregulation of GPR41 and suppression of the ERK/JNK/NF-κB pathway, which might provide an alternative therapy strategy of AD.