Search Results (143)

Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut–brain interactions. Full article

Short-chain fatty acids (SCFA), particularly propionate and butyrate, reduce food intake, body weight, and modulate gut microbiota composition. However, it is unclear whether encapsulation of propionate and butyrate enhances their delivery to distal gut to improve energy balance and gut microbiota composition in obesity. Objectives: We determined the effects of microencapsulated propionate and butyrate on energy balance, gut microbiota and metabolite composition in obese rats. Methods: In experiment-1, obese male Sprague-Dawley rats were fed microencapsulated propionate and butyrate (5–10% wt/wt) or control high-fat diet. In experiment-2, obese rats were fed 10% microencapsulated propionate and butyrate, non-encapsulated butyrate (10% wt/wt), and pair-fed to non-capsulated butyrate. Food intake, energy expenditure (EE), sympathetic-mediated EE changes by propranolol, body composition, gut microbiota and fecal and plasma metabolites were analyzed. Results: Microencapsulated propionate decreased caloric intake, weight and fat mass, while microencapsulated butyrate had modest effects. Non-encapsulated butyrate reduced intake and prevented weight gain beyond pair-fed controls. Microencapsulated propionate and non-encapsulated butyrate reduced respiratory quotient suggestive of a shift towards lipid utilization, and enhanced β-adrenergic-mediated EE. Microencapsulated propionate and butyrate altered alpha and beta diversity metrics, microencapsulated propionate increased Verrucomicrobiae, microencapsulated butyrate increased Lactobacillaceae, and microencapsulated propionate and butyrate reduced Erysipelotrichia. Microencapsulated propionate and butyrate increased fecal amino acids and altered select plasma metabolites; microencapsulated propionate increased fecal and plasma propionate, supporting distal gut delivery. Conclusions: Dietary supplementation with microencapsulated propionate and butyrate improved energy balance, enhanced lipid utilization, beneficially modulated gut microbiota composition, and altered metabolite profiles in obese rats. Full article

This study elucidates the mechanisms underlying the positive effect of glyceryl monolaurate (GML) on fetal intrauterine development via maternal gut-microbiota modulating effects using a sow model. Addition of GML (1000 mg/kg) improved neonatal intestinal conditions (jejunal villus height, VH/CD ratio and tight junctions) and dorsal longissimus muscle (MyoD, MyoG and MSTN) development in the GML-treated group. Furthermore, GML improved maternal gut microbiota composition by enriching short-chain fatty acid (SCFA)-producing bacteria Lactobacillus and Akkermansia. Meanwhile, SCFA concentrations in sow feces and newborn plasma, as well as their receptors (GPR41/43) in intestine and muscle were upregulated with GML, corresponding with enhanced antioxidative and anti-inflammatory capacity. Further correlation analysis revealed Akkermansia and Lactobacillus positively correlated with SCFAs, antioxidative indicators, and anti-inflammatory capacity markers. Moreover, GML inhibited the activation of the MAPK/NF-κB inflammatory signaling pathway. In summary, GML enhanced fetal intrauterine development by modulating sow intestinal SCFA-producing bacteria. Full article

The association of gut microbiota with lymph node tuberculosis (LNTB) remains unexplored. This study employed metagenomic sequencing and plasma metabolomics analyses to investigate the role of gut microbiota in LNTB patients. Significant alterations in gut microbial diversity were observed in LNTB patients, characterized by a notable reduction in bacterial taxa involved in short-chain fatty acid (SCFA) synthesis, including Ruminococcus, Faecalibacterium, Roseburia, and Blautia, compared to healthy individuals. KEGG pathway analysis further revealed that gut dysbiosis could negatively impact SCFA biosynthesis and metabolism. Plasma metabolomics demonstrated disruptions in metabolites associated with SCFA synthesis and inflammation pathways in the LNTB group. Integrated analysis indicated significant correlations between specific gut microbiota (Blautia, Butyricicoccus, Coprococcus, Ruminococcus, Bacteroides, Clostridium) and plasma metabolites, including α-benzylbutyric acid, acetic acid, and succinic acid. Our findings demonstrate that gut microbiota dysbiosis and related metabolic dysfunction significantly reduce SCFA production in LNTB patients, potentially identifying novel therapeutic targets for LNTB management. Full article

This study aimed to investigate the effects of dietary ISF:SF ratio on reproductive performance, biochemical parameters, colostrum composition, and fecal microbial composition in gestating sows. A total of 30 multiparous sows were randomly allocated to three dietary treatment groups: 8% inulin diet (ISF:SF 1.14, Inulin group), 8% cotton fiber diet (ISF:SF 6.61, Cotton group), and 4% inulin + 4% cotton fiber diet (ISF:SF 2.37, Inulin + Cotton group). The results showed that, compared to the other groups, the Inulin group had a significantly higher number of piglets born alive, as well as increased plasma concentrations of acetic acid, butyric acid, hexanoic acid, and total short-chain fatty acids (SCFAs) (p < 0.05). Sows in the Inulin group had significantly lower fecal scores than those in the other groups from days 81 to 85 and from days 106 to 110 of gestation (p < 0.05). On day 90 of gestation, the serum levels of albumin, urea, uric acid, calcium, and phosphorus in the Inulin group were significantly lower than those in the other groups (p < 0.05). Additionally, the serum levels of triacylglycerol in the Inulin + Cotton Fiber group were significantly higher than those in the other groups (p < 0.05). However, there were no significant differences in serum concentrations of total protein, creatinine, glucose, cholesterol, HDL-cholesterol, or LDL-cholesterol among the treatments (p > 0.05). On day 110 of gestation, the serum content of urea, uric acid, calcium, and phosphorus in the Inulin group was significantly lower than those in the other groups (p < 0.05). Furthermore, the plasma levels of uric acid, triacylglycerol, and HDL-cholesterol in the Inulin + Cotton Fiber group were significantly higher than those in the Cotton Fiber group (p < 0.05), while the creatinine levels in the Inulin group were higher than those in the other groups (p < 0.05). No differences were observed in the composition and immune performance of colostrum (p > 0.05). Microbial sequencing analysis showed that dietary inulin supplementation to increase the proportion of soluble fiber significantly decreased the abundance of Firmicutes, Clostridia, Clostridiales, Lachnospiraceae, Streptococcaceae, and Streptococcus (p < 0.05). The abundance of short-chain fatty acid-producing microorganisms—Bacteroidetes, Bacteroidia, Bacteroidales, and Muribaculaceae—was significantly increased (p < 0.05). The results indicated that inulin supplementation decreased the dietary ISF:SF ratio, significantly alleviated constipation in sows, increased the number of piglets born alive, regulated intestinal microecology, and increased the plasma concentrations of short-chain fatty acids (SCFAs), including acetic, propionic, and butyric acids. Full article

Short-chain fatty acids (SCFAs) are microbial metabolites involved in immune regulation, energy metabolism, and intestinal barrier integrity. Among them, the role of hexanoic acid (C6), predominantly derived from dietary sources, remains poorly understood in chronic heart failure (CHF) and sarcopenia. A total of 636 patients with confirmed CHF were screened between 2019 and 2021. Sarcopenia was diagnosed in 114 patients, with 74 meeting the inclusion criteria for analysis. Plasma levels of SCFAs—including butanoic, propanoic, isobutyric, 2- and 3-methylbutanoic, hexanoic, pentanoic, and 4-methylpentanoic acids—were measured using HPLC-MS/MS. Muscle strength, mass, and physical performance were assessed using handgrip dynamometry, bioelectrical impedance analysis, and SPPB, respectively. All patients showed elevated SCFA levels compared to reference values. Butanoic acid levels exceeded reference values by 32.8-fold, propanoic acid by 10.9-fold, and hexanoic acid by 1.09-fold. Patients with plasma hexanoic acid levels above the 50th percentile had a seven-fold increased mortality risk (OR = 7.10; 95% CI: 1.74–28.9; p < 0.01). Kaplan–Meier analysis confirmed significantly lower survival in this group (p = 0.00051). The mean left ventricular ejection fraction was 41.2 ± 7.5%, and the mean SPPB score was 6.1 ± 1.8, indicating impaired physical performance. Elevated plasma hexanoic acid is associated with poor prognosis in CHF patients with sarcopenia. These findings suggest that C6 may serve as a potential prognostic biomarker and therapeutic target in this population. Full article

Background: Short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) are human metabolites which are involved in various biochemical processes and can offer valuable insights and information on various pathological and metabolic issues of patients. Accurate, precise, high-performance bioanalytical methods are important tools in both research and diagnostics of many pathologies, with LC-MS being the most frequently used methodology in modern metabolomics studies. Methods: The current paper describes a complete LC-MS/MS methodology for the accurate quantification of total plasmatic SCFA concentrations in humans using high-resolution QTOF mass spectrometric detection, including sample cleanup, preparation, and derivatization. Results and Conclusions: The method was validated with regard to all relevant parameters (selectivity, sensitivity, accuracy, precision, linearity, recovery, carryover, and reproducibility of sample preparation) according to the current applicable guidelines and tested in an in vivo study to quantify peripheral SCFAs in human patients as biomarkers for gut–brain axis disruption. Full article

The aim of this research was to provide a comparative analysis of the major parameters of the blood lipid spectrum found both in the case of brain tumors and in atherosclerosis, as well as to assess the correlation of these indicators with the proliferative activity index Ki-67 in cells. Blood analyses were conducted on samples from 50 patients with brain tumors and 50 patients with cerebral atherosclerosis. Blood plasma from 50 essentially healthy people was used for controls. Significant differences were found in the parameter values between the atherosclerosis sufferers and the control group only for their ratios of neutral lipids to cholesterol. Of the short-chain fatty acids, butyric acid is of greatest interest due to the significant differences of its levels from the control group in the blood of both patients with meningiomas and of those with gliomas. Statistically significant correlation coefficients between the levels of the Ki-67 cell proliferation marker and, in particular, butyric acid were found when compared with the neutral lipids to cholesterol ratios. These identified parameters of the blood plasma lipid spectrum can be used for preoperative diagnostics of brain tumors. However, these ratios cannot be used as preoperative noninvasive predictors of the level of the Ki-67 mitotic index, as no significant differences corresponding to this were found for low-grade or for high-grade anaplasia of brain tumors. Full article

Background: Plastic production has led to widespread microplastic (MP) pollution, with children more vulnerable to MPs than adults. However, the mechanisms linking MP exposure to hypertension and kidney disease in children remain unclear. This study explored whether sodium butyrate, a short-chain fatty acid (SCFA) with antioxidant and anti-inflammatory properties, could mitigate MP-induced hypertension and kidney damage in juvenile rats. Methods: Male Sprague-Dawley rats (3 weeks old) were randomly assigned to four groups (n = 8/group): control, low-dose MP (1 mg/L), high-dose MP (10 mg/L), and high-dose MP with sodium butyrate (400 mg/kg/day). Rats were euthanized at 12 weeks. Results: High-dose MP exposure impaired kidney function and increased blood pressure, which were alleviated by sodium butyrate through reduced oxidative stress, modulation of gut microbiota, increased plasma butyric acid levels, and enhanced renal SCFA-sensing G protein-coupled receptor 43 expression. Conclusions: Sodium butyrate holds potential for mitigating MP-induced hypertension by reducing oxidative stress, modulating the gut microbiota, and elevating butyric acid levels. Full article

Background: Incidence of cardiometabolic disease among U.S. Hispanics/Latinos is higher than in non-Hispanic Whites. Prolonged sitting duration is prevalent in older adults, and compounded with menopause, greatly increases cardiometabolic risk in postmenopausal women. Metabolomic analyses of interventions to reduce sitting are lacking and mechanistic understanding of health-promoting behavior change in postmenopausal Latinas is needed. Methods: To address this knowledge gap, an exploratory analysis investigated the plasma metabolome impact of a 12-week increased standing intervention among sedentary postmenopausal Latinas with overweight or obesity. From a parent-randomized controlled trial, a subset of Best Responders (n = 43) was selected using parameters of highest mean change in sitting bout duration and total sitting time; baseline variable-Matched Controls (n = 43) were selected using random forest modeling. Targeted LC-MS/MS analysis of archived baseline and 12-week plasma samples was conducted. Metabolite change was determined using a covariate-controlled general linear model and multivariate testing was performed. A false discovery rate correction was applied to all analyses. Results: Best Responders significantly changed time sitting (−110.0 ± 11.0 min; −21%), standing (104.6 ± 10.1 min; 40%), and sitting in bouts >30 min (−102.3 ± 13.9 min; −35%) compared to Matched Controls (7.1 ± 9.8 min, −7.8 ± 9.0 min, and −4.6 ± 12.7 min, respectively; all p < 0.001). Twelve-week metabolite change was significantly different between the two groups for 24 metabolites (FDR < 0.05). These were primarily related to amino acid metabolism, improved blood flow, and ATP production. Enzyme enrichment analysis predicted significant changes regulating glutamate, histidine, phenylalanine, and mitochondrial short-chain fatty acid catabolism. Pathway analysis showed significant intervention effects on glutamate metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis, potentially indicating reduced cardiometabolic disease risk. Conclusions: Replacing nearly two hours of daily sitting time with standing and reduced prolonged sitting bouts significantly improved metabolomic profiles associated with cardiometabolic risk among postmenopausal Latinas. Full article

Conjugation of short-chain fatty acids (SDFAs) to amines containing ring structures allows for better measurement by liquid chromatography tandem mass spectroscopy (LC-MS/MS). However, collision-induced dissociation (CID) results in breaking the conjugate back to the original SCFA and amine. We therefore set out to find an amine that would remain on the SCFA after CID and create a unique daughter for selectivity of measurement. Of twenty-seven amines with ring structures, we found four that contain bicycle-type structures (two rings connected by a carbon) with nitrogen in the second ring. CID removes the second ring at the nitrogen, leaving the first ring on the daughter. Of the four amines, 4-(pyrrolidine-1-ylmethyl) benzylamine (4PyBA) showed the strongest conjugation. Conjugation of 4PyBA to SCFA (C3–C6), their isomers and their phenylated versions (and isomers) resulted in good chromatographic peaks and separation. CID resulted in unique daughters that allowed for selectivity of measurement. Using this method, standard curves were generated that show good linearity (r2 > 0.99) in the nM and μM range with lower limits of detection between 40 and 229 nM for a 10 μL sample. Finally, we used this method to measure SCFA in plasma, liver, platelets, and red blood cells, demonstrating its use in biological systems. Because SCFAs are an index of microbiome diversity in the gastrointestinal track, this method will allow us to study changes in SCFAs and the microbiome in pathologic conditions including trauma, hemorrhage, and sepsis. Full article

Yeast fermentation products (YFPs) are known to contain bioactive compounds, such as nutritional metabolites and cell wall polysaccharides (specifically glucan and mannan), which have been demonstrated to exert positive effects on the growth performance and immunity of livestock and poultry. However, the impact of YFPs on intestinal inflammation and microflora composition in pigs infected with Salmonella typhimurium remains unclear. To investigate this, a total of 18 weaned pigs were divided into three treatment groups: a non-challenged control group (Con), a group challenged with Salmonella typhimurium (ST), and a group challenged with Salmonella typhimurium and supplemented with 0.4% YFP (YFP). The experiment spanned five weeks, encompassing a period of 21 days prior to and 14 days subsequent to the initial Salmonella typhimurium challenge. The findings indicated that the YFP group exhibited an increase in average daily gain (ADG) and a decrease in the feed-gain ratio (F/G) in comparison to the ST group following the Salmonella challenge. Additionally, the YFP group demonstrated a reduction in the levels of inflammatory cytokines in plasma and a decrease in the expression of inflammatory genes in the colon. Treatment with YFP also resulted in improved colon histomorphology, heightened alpha diversity of the gut microbiota, augmented the abundance of butyrate-producing bacteria, and elevated concentrations of short-chain fatty acids (SCFAs). In addition, YFP reprogrammed energy metabolism in colon epithelial cells by blunting glycolysis. Together, dietary YFP supplementation alleviated colon inflammation in weaned pigs challenged with Salmonella typhimurium, and shaped the beneficial microbiota, thereby maintaining gut homeostasis. The results provided evidence supporting the application of yeast fermentation products in livestock production. Full article

Background: Cactus contains dietary fiber and minerals and is expected to have preventive effects against diabetes, arteriosclerosis, and other diseases. Additionally, cactus intake induces the production of short-chain fatty acids derived from the gut microbiota, which might influence immune functions. In this study, we examined the effects of a cactus (Nopalea cochenillifera: NC)-supplemented diet on lipopolysaccharide (LPS)-induced immune responses and intestinal barrier function. Methods: Male C3H/HeN mice were randomly divided into three groups—no fiber (NF), cellulose-containing fiber (Cellu), and cactus-added (NC) diets—for 6 weeks. The TNF-α and IL-10 responses to LPS, antibody titers, and intestinal barrier function, as well as the fecal microbiota, were analyzed. Results: The plasma TNF-α but not the IL-10 concentrations were significantly higher in the NC group than in the NF and Cellu groups. Furthermore, the plasma IgG antibody titers were significantly higher in the NC group than in the other groups. The NC group showed higher mucin content and IgA antibody titers in their feces compared with the Cellu group. The succinate and lactate contents, which induce a reduction in TNF-α secretion by macrophages, in the cecum of the NC group were significantly lower than those in the Cellu and NF groups. In contrast, the butyrate content was significantly higher in the cecum of the NC group compared to that of the Cellu group, with a significantly higher relative abundance of butyrate-producing bacteria. Conclusions: Taken together, we found that cactus intake regulates innate and adaptive immune function via the gut microbiota in mice. Therefore, cactus supplementation might serve as a strategy to develop novel functional foods with dietary fiber. Full article

Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype. However, it is not known whether changes in SCFA levels, especially acetate, occurred during the canalicular or early saccular phase among pregnant women whose children did not develop asthma. Methods: In this research, we investigated this question using plasma samples obtained from mothers during the 20th and 28th weeks of pregnancy. Mothers whose children developed asthma were categorized as cases, while those whose children did not were categorized as controls. The specimens were assayed for a panel of SCFAs consisting of acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate. Results: The resulting data indicated no significant differences between the cases and controls, either at week 20 or week 28, in any of the SCFAs measured, despite the vascularization during these phases. Conclusions: We did not find differences in measured SCFAs at week 20 or at week 28. A larger prospective study covering multiple time points is necessary to confirm the findings of this preliminary study. Such a study, together with the published literature regarding later time points, may help discover critical windows during pregnancy when simple manipulation of diet will result in healthier outcomes for infants. Full article

Background/Objectives: Probiotics have great potential in improving acute alcohol intoxication. The aim of this study was to investigate the mitigating effect and mechanism of action of Weizmannia coagulans BC99 on acute alcohol intoxication (AAI) in SD rats. Methods: BC99 was divided into different doses administered by gavage to rats, and a rat model of acute alcohol intoxication was established by multiple gavages of excess alcohol. Results: Our study demonstrated that W. coagulans BC99 intervention significantly prolonged the latency period of intoxication; significantly attenuated alcohol-induced lipid elevation, liver injury, hepatic inflammation, and intestinal barrier damage; and lowered plasma endotoxin (LPS) levels in rats. In addition, W. coagulans BC99 could effectively restore the balance of intestinal flora, increase the abundance of Lachnospiraceae_NK4A136, Prevotellaceae_NK3B31, Parabacteroides, and Ralstonia, and thus increase the content of intestinal short-chain fatty acids (SCFAs), especially butyric acid. Moreover, we demonstrated through sodium butyrate validation experiments that butyrate could attenuate intestinal barrier damage and reduce the diffusion of LPS, thereby reducing liver inflammation. Conclusions: In conclusion, W. coagulans BC99 ameliorates acute alcohol intoxication in rats by increasing the abundance of butyrate-producing genera and thereby increasing butyrate abundance to alleviate intestinal barrier injury. Full article