Fecal Short-chain Fatty Acids Research Articles

Fecal short chain fatty acids role in atrial fibrillation paroxysm pathogenesis through coronary artery disease patients

gut microbiota composition and its metabolites is an essential part of human health. Short chain fatty acids (SCFA) are known gut microbiota metabolites. Lack of them is common for dyslipidemia and inflammatory changes. But their role in atrial fibrillation (AF) and coronary artery disease (CAD) pathogenesis is still uninvestigated. The aim: to estimate the fecal short chain fatty acids changes in patients with atrial fibrillation paroxysm and coronary artery disease and found their connections with known cardiometabolic risk factors. Materials and methods: 300 patients were investigated. We divided them into 3 groups: I group – 149 CAD patients without rhythm disorders, II group – 124 patients with CAD and AF paroxysm and control group (CG) – 27 patients without CAD and arrhythmias. Fecal SCFA was checked by gas chromatography with mass electron detection. Results: Fecal SCFA changes in patients with AF paroxysm and CAD were found in our investigation. Isocaproic and isobutyric fecal acids appears in CAD and AF patients’ samples in comparison with control group. In the patients with AF and CAD significant increasing of valeric (1128,43%) and decreasing butyric (78,75%), isovaleric (56,29%), caprylic (99,21%) acids, medium chain fatty acids (95,54%) and unsaturated fatty acids (38,76%) levels was revealed in comparison with CAD patients without arrhythmias (P<0,05). The largest amount of correlations was between total amount of SCFA, medium chain fatty acids (total amount = 7), butyric acid (total number = 6) and cardiometabolic risk factors (P<0,05). The acceptable role of total amount of short chain fatty acids (AUC = 0.7907) and butyric acid (AUC=0.7127) in AF paroxysm occurrence in CAD patients was proven by ROC-analysis. Conclusions: SCFA-synthesis violations were reveled in patients with atrial fibrillation paroxysm and coronary artery disease. To propose the new ways of gut microbiota and cardiometabolic risk factors correction will be interesting for future investigations.

First Exploration of the Altered Microbial Gut–Lung Axis in the Pathogenesis of Human Refractory Chronic Cough

PurposeCough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut–lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM).Methods16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances.ResultsIn comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC.ConclusionSince differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut–lung communication.

XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner.

Differences in male vs. female immune responses are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones are well established, the contributions of sex chromosome complement (XX vs. XY) and gut microbiome diversity on immune sexual dimorphisms have only recently become appreciated. Here we investigate the individual and collaborative influences of sex chromosome complements and gut microbiota on humoral immune activation. Male and female Four Core Genotype (FCG) mice were immunized with heat-killed Streptococcus pneumoniae (HKSP). Humoral immune responses were assessed, and X-linked immune-related gene expression was evaluated to explain the identified XX-dependent phenotype. The functional role of Kdm6a, an X-linked epigenetic regulatory gene of interest, was evaluated ex vivo using mitogen stimulation of B cells. Additional influences of the gut microbiome on sex chromosome-dependent B cell activation was also evaluated by antibiotically depleting gut microbiota prior to HKSP immunization. Reconstitution of the depleted microbiome with short-chain fatty acid (SCFA)-producing bacteria tested the impact of SCFAs on XX-dependent immune activation. XX mice exhibited higher HKSP-specific IgM-secreting B cells and plasma cell frequencies than XY mice, regardless of gonadal sex. Although Kdm6a was identified as an X-linked gene overexpressed in XX B cells, inhibition of its enzymatic activity did not affect mitogen-induced plasma cell differentiation or antibody production in a sex chromosome-dependent manner ex vivo. Enhanced humoral responses in XX vs. XY immunized FCG mice were eliminated after microbiome depletion, indicating that the microbiome contributes to the identified XX-dependent immune enhancement. Reconstituting microbiota-depleted mice with select SCFA-producing bacteria enhanced fecal SCFA concentrations and increased humoral responses in XX, but not XY, FCG mice. However, exposure to the SCFA propionate alone did not enhance mitogenic B cell stimulation in ex vivo studies. FCG mice have been used to assess sex hormone and sex chromosome complement influences on various sexually dimorphic traits. The current study indicates that the gut microbiome impacts humoral responses in an XX-dependent manner, suggesting that the collaborative influence of gut bacteria and other sex-specific factors should be considered when interpreting data aimed at delineating the mechanisms that promote sexual dimorphism.

Nutrient Composition and Feed Hygiene of Alfalfa, Comparison of Feed Intake and Selected Metabolic Parameters in Horses Fed Alfalfa Haylage, Alfalfa Hay or Meadow Hay.

The aim of this study was to examine the nutrient composition and feed hygiene of alfalfa as well as investigate the feed intake, blood, urine and faecal parameters of horses fed alfalfa haylage (AS) compared with alfalfa hay (AH) and meadow hay (MH). A total of 11 geldings were fed ad libitum (2.1% dry matter (DM) of body weight (BW)) with alfalfa haylage, alfalfa hay and meadow hay (MH) in a Latin square design. On days 0 and 21 of the feeding period, blood samples were analysed for kidney and liver parameters. Faecal samples were analysed for pH, DM and short-chain fatty acids (SCFAs). Spontaneous urine was collected during the feeding period to analyse selected parameters. Forage was analysed in terms of feed hygiene and crude nutrients. In several feed samples of AS, AH and MH, the microbial reference ranges were exceeded for product-typical and spoilage-indicating bacteria and fungi. Crude nutrient analyses revealed a median crude protein content of 139 (138/142) g/kg DM for AS, which was similar to that in AH (127-135 g/kg DM) and substantially higher than in MH (79.1-87.7 g/kg DM). The calcium level in AS (11.3 g/kg DM) was significantly higher than that in MH (4.00-4.95 g/kg DM) but not compared with that in AH (9.80-10.4 g/kg DM). All blood parameters were within the reference ranges. Fractional excretion (FE)Ca for AS-fed horses ranged from 8.13 to 22.0%; the FECa for AH-fed horses ranged from 6.48 to 24.8%; the FECa for MH-fed horses ranged from 6.69 to 53.2%. No significant differences were found in faecal pH or SCFA content in AS-fed horses compared with AH-fed and MH-fed horses. We concluded that alfalfa haylage provides an alternative forage for equine nutrition.

Exploring the Role of Inulin in Targeting the Gut Microbiota: An Innovative Strategy for Alleviating Colonic Fibrosis Induced By Irradiation.

The use of radiation therapy to treat pelvic and abdominal cancers can lead to the development of either acute or chronic radiation enteropathy. Radiation-induced chronic colonic fibrosis is a common gastrointestinal disorder resulting from the above radiation therapy. In this study, we establish the efficacy of inulin supplements in safeguarding against colonic fibrosis caused by irradiation therapy. Studies have demonstrated that inulin supplements enhance the proliferation of bacteria responsible to produce short-chain fatty acids (SCFAs) and elevate the levels of SCFAs in feces. In a mouse model of chronic radiation enteropathy, the transplantation of gut microbiota and its metabolites from feces of inulin-treated mice were found to reduce colonic fibrosis in validation experiments. Administering inulin-derived metabolites from gut microbiota led to a notable decrease in the expression of genes linked to fibrosis and collagen production in mouse embryonic fibroblast cell line NIH/3T3. In the cell line, inulin-derived metabolites also suppressed the expression of genes linked to the extracellular matrix synthesis pathway. The results indicate a novel and practical approach to safeguarding against chronic radiation-induced colonic fibrosis.

Short term supplementation with cranberry extract modulates gut microbiota in human and displays a bifidogenic effect

Cranberry is associated with multiple health benefits, which are mostly attributed to its high content of (poly)phenols, particularly flavan-3-ols. However, clinical trials attempting to demonstrate these positive effects have yielded heterogeneous results, partly due to the high inter-individual variability associated with gut microbiota interaction with these molecules. In fact, several studies have demonstrated the ability of these molecules to modulate the gut microbiota in animal and in vitro models, but there is a scarcity of information in human subjects. In addition, it has been recently reported that cranberry also contains high concentrations of oligosaccharides, which could contribute to its bioactivity. Hence, the aim of this study was to fully characterize the (poly)phenolic and oligosaccharidic contents of a commercially available cranberry extract and evaluate its capacity to positively modulate the gut microbiota of 28 human subjects. After only four days, the (poly)phenols and oligosaccharides-rich cranberry extract, induced a strong bifidogenic effect, along with an increase in the abundance of several butyrate-producing bacteria, such as Clostridium and Anaerobutyricum. Plasmatic and fecal short-chain fatty acids profiles were also altered by the cranberry extract with a decrease in acetate ratio and an increase in butyrate ratio. Finally, to characterize the inter-individual variability, we stratified the participants according to the alterations observed in the fecal microbiota following supplementation. Interestingly, individuals having a microbiota characterized by the presence of Prevotella benefited from an increase in Faecalibacterium with the cranberry extract supplementation.

Short-chain fatty acids in plasma and feces: An optimized and validated LC-QqQ-MS method applied to study anorexia nervosa

Short-chain fatty acids (SCFAs) are organic saturated monocarboxylic acids with fewer than six carbon atoms. Their recently described relevance in health and disease has brought to the table the need for a convenient method for their analysis. The current research presents an optimized and validated LC-QqQ-MS method for the absolute quantification of SCFAs in plasma and feces. This method has proven to be accurate and precise in a wide range of concentrations (0.2 – 200 µM). It has been applied to more than 500 samples showing good precision, reproducibility, and linearity results. The method was applied to study samples from anorexia nervosa (AN) patients and matched healthy controls (HC). The results showed significant differences in the concentration of plasmatic and fecal SCFAs between both groups whose implications in AN are yet to be determined. Nonetheless, these findings denote important alterations in the SCFAs homeostasis in AN which can be linked to the metabolic alterations and the intestinal dysbiosis already characterized in the disease. More research is still required to identify the function of these metabolites in the pathophysiology of AN, but the present work provides a reliable methodology and valuable information to continue delving into the potential role of the microbiota as a therapeutic target via the gut-brain axis.

Effects of chronic unpredictable mild stress on gut microbiota and fecal amino acid and short-chain fatty acid pathways in mice

Depression is a serious disease that has a significant impact on social functioning. However, the exact causes of depression are still not fully understood. Therefore, it is necessary to explore new pathways leading to depression. In this study, we used 16 S rDNA to examine changes in gut microbiota and predict related pathways in depression-like mice. Additionally, we employed liquid chromatography-mass spectrometry (LC-MS) to identify changes in amino acids and gas chromatography-mass spectrometry (GC-MS) to identify changes in short-chain fatty acids (SCFAs) in fecal samples. We conducted Pearson/Spearman correlation analysis to investigate the associations between changes in amino acids/SCFAs and behavioral outcomes. The 16 S rDNA sequencing revealed significant alterations in gut microbiota at the phylum and genus levels in mice subjected to chronic unpredictable mild stress (CUMS). The relative abundances of Bacteroidetes, Proteobacteria, Bacteroides, and Alloprevotella were increased, while Firmicutes, Verrucomicrobia, Actinobacteria, Lactobacillus, Akkermansia, Lachnospirillum, and Enterobacter were decreased in the CUMS mice. We used PICRUSt software to annotate the kyoto encyclopedia of genes and genomes (KEGG) pathway function related to depression-like behavior in mice. Our analysis identified sixty functional pathways associated with the gut microbiota of mice exhibiting depression-like behavior. In the amino acid concentration analysis, we observed decreased levels of hydroxyproline and tryptophan, and increased levels of alanine in CUMS mice. In the SCFAs concentration assay, we found decreased levels of butyric acid and valeric acid, and increased levels of acetic acid in CUMS mice. Some of these changes were significantly correlated with depressive-like behaviors. Our study contributes to the understanding of the mechanism of the gut-brain axis in the occurrence and development of depression.

Fructooligosaccharides Supplementation: A Good Choice for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease?

Background and objectives: Carbohydrates such as fructooligosaccharides (FOSs) are associated with improved gastrointestinal health and the prevention of excess body fat. We evaluated the long-term effects of high amounts of FOS on metabolic parameters, non-alcoholic fatty liver disease (NAFLD) and short-chain fatty acids (SCFAs). Methods: Sixty C57BL/6 mice received the following diets for four months: control (C), normolipid rich in fiber (F), normolipid supplemented with FOS (FOS), high fat (HL), high fat with high fiber (HLF) and high fat with FOS (HLFOS). We analyzed the animal weight; body composition; food intake; fasting blood glucose; serum and liver lipid profiles; liver and intestinal histologies; malondialdehyde (MDA), hepatic retinol and α-tocopherol; and SCFAs in the feces. Results: Supplementation with FOS in a high-fat diet promoted less body weight gain and reduced liver and retroperitoneal adipose tissue weights compared to HL and HF. FOS prevented NASH and decreased alanine aminotransferase and serum cholesterol levels in experimental animal models of obesity and metabolic syndrome (MS). There were statistical differences found in the dosages of the three main SCFAs in feces (acetic, isobutyric and isovaleric acids). Conclusions: Long-term supplementation with high doses of FOS was effective in reducing weight, adiposity, NAFLD and serum cholesterol in C57BL mice with obesity and MS induced by a high-fat diet.

Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum

BackgroundColonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics.MethodsThe gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC–MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut.ResultsThe gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day.ConclusionWe suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

Association of short-chain fatty acids and the gut microbiome with type 2 diabetes: Evidence from the Henan Rural Cohort

Background and aimsHuman studies about short-chain fatty acids (SCFAs), the gut microbiome, and Type 2 diabetes (T2DM) are limited. Here we explored the association between SCFAs and T2DM and the effects of gut microbial diversity on glucose status in rural populations. Methods and resultsWe performed a cross-sectional study from the Henan Rural Cohort and collected stool samples. Gut microbiota composition and faecal SCFA concentrations were measured by 16S rRNA and GC-MS. The population was divided based on the tertiles of SCFAs, and logistic regression models assessed the relationship between SCFAs and T2DM. Generalized linear models tested the interactions between SCFAs and gut microbial diversity on glucose indicators (glucose, HbAlc and insulin). Compared to the lowest tertile of total SCFA, acetate and butyrate, the highest tertile exhibited lower T2DM prevalence, with ORs and 95% CIs of 0.291 (0.085–0.991), 0.160 (0.044–0.574) and 0.171 (0.047–0.620), respectively. Restricted cubic spline demonstrated an approximately inverse S-shaped association. We also noted interactions of the ACE index with the highest tertile of valerate on glucose levels (P-interaction = 0.022) and the Shannon index with the middle tertile of butyrate on insulin levels (P-interaction = 0.034). Genus Prevotella_9 and Odoribacter were inversely correlated with T2DM, and the genus Blautia was positively associated with T2DM. These bacteria are common SCFA-producing members. ConclusionsInverse S-shaped associations between SCFAs (total SCFA, acetate, and butyrate) and T2DM were observed. Valerate and butyrate modify glucose status with increasing gut microbial diversity.

Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson's Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs.

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson's disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy.

Association between fecal short-chain fatty acid levels and constipation severity in subjects with slow transit constipation.

We measured the fecal levels of short-chain fatty acids (SCFAs) in subjects with slow transit constipation (STC) and assessed the correlation between SCFA levels and disease severity as well as quality of life. We isolated the supernatant from fecal samples of healthy and STC subjects and measured the SCFA levels. To assess the correlation between fecal SCFA levels and disease severity as well as quality of life, we used the Constipation Scoring System, Patient Assessment of Constipation Symptoms, and Patient Assessment of Constipation Quality of Life questionnaires. 16 STC subjects and 16 healthy controls were enrolled. STC subjects had lower SCFA levels, but the difference was not statistically significant (475.85 ± 251.68 vs. 639.77 ± 213.97 µg/ml, P = 0.056). Additionally, STC subjects had lower acetic and propionic acid levels (149.06 ± 88.54 vs. 261.33 ± 109.75 µg/ml and 100.60 ± 60.62 vs. 157.34 ± 66.37 µg/ml, respectively, P < 0.05) and higher isobutyric and isovaleric acid levels (27.21 ± 15.06 vs. 18.16 ± 8.65 µg/ml and 31.78 ± 18.81 vs. 16.90 ± 10.05 µg/ml, respectively, P < 0.05). At 252.21 µg/ml acetic acid, the specificity and sensitivity to distinguish healthy from STC subjects were 93.7% and 56.3%, respectively. In STC subjects, there were significant negative correlations between acetic and propionic acid levels and Constipation Scoring System scores. Fecal SCFA, acetic acid, and propionic acid levels decreased in STC subjects. There were significant negative correlations between the levels of the two acids and constipation severity.

Alteration of gut microbiota in post-stroke depression patients with Helicobacter pylori infection

Background: Several studies have identified an association between the gut microbiome and post-stroke depression(PSD), and Helicobacter pylori(H. pylori) infection cause significant alterations in the composition of the gastrointestinal microbiome. However, evidence regarding the role of the H. pylori infection in promoting PSD is still lacking. Here, we conducted a retrospective study to explore risk factors associated with PSD.Methods: Patients with cerebral infarction were consecutively enrolled from December 2021 to October 2022. The diagnosis of PSD is based on the DSM-V criteria, and the Hamilton Depression Rating Scale(HAMD) was used to identify patients with PSD. White matter lesions were evaluated using magnetic resonance imaging(MRI) and H. pylori infection was detected by 13C-urea breath test. Further, 16S rRNA gene sequencing was used to evaluate the changes in gut microbiota composition of fecal samples from PSD patients. The concentration of short-chain fatty acids(SCFAs) was determined by gas chromatography–mass spectrometry(GC–MS).Results: Multivariate regression analysis showed that deep white matter lesions(DWMLs) [odds ratio(OR) 3.382, 95% confidence interval(CI) 1.756–6.512; P = 0.001] and H. pylori infection(OR 2.186, 95% CI 1.149–4.159; P = 0.017) were the independent risk factors for PSD. Patients with H. pylori infection had more severe depressive symptoms than patients without infection. Intestinal microbiota was significantly different between H. pylori-positive PSD[H. pylori(+)] patients and H. pylori-negative PSD[H. pylori (−)] patients. Fecal SCFAs concentrations were significantly reduced in the H. pylori(+) group compared to the negative ones.Conclusion: DWMLs and H. pylori infection may play important roles in the development of PSD. H. pylori infection is likely to be involved in the pathogenesis of PSD by altering the intestinal flora.

Dynamics of Gut Microbiota and Short-Chain Fatty Acids during a Cycling Grand Tour Are Related to Exercise Performance and Modulated by Dietary Intake.

Regular exercise has been described to modify both the diversity and the relative abundance of certain bacterial taxa. To our knowledge, the effect of a cycling stage race, which entails extreme physiological and metabolic demands, on the gut microbiota composition and its metabolic activity has not been analysed. The aim of this cohort study was to analyse the dynamics of faecal microbiota composition and short-chain fatty acids (SCFAs) content of professional cyclists over a Grand Tour and their relationship with performance and dietary intake. 16 professional cyclists competing in La Vuelta 2019 were recruited. Faecal samples were collected at four time points: the day before the first stage (A); after 9 stages (B); after 15 stages (C); and on the last stage (D). Faecal microbiota populations and SCFA content were analysed using 16S rRNA sequencing and gas chromatography, respectively. A principal component analysis (PCA) followed by Generalised Estimating Equation (GEE) models were carried out to explore the dynamics of microbiota and SCFAs and their relationship with performance. Bifidobacteriaceae, Coriobacteriaceae, Erysipelotrichaceae, and Sutterellaceae dynamics showed a strong final performance predictive value (r = 0.83, ranking, and r = 0.81, accumulated time). Positive correlations were observed between Coriobacteriaceae with acetate (r = 0.530) and isovalerate (r = 0.664) and between Bifidobacteriaceae with isobutyrate (r = 0.682). No relationship was observed between SCFAs and performance. The abundance of Erysipelotrichaceae at the beginning of La Vuelta was directly related to the previous intake of complex-carbohydrate-rich foods (r = 0.956), while during the competition, the abundance of Bifidobacteriaceae was negatively affected by the intake of simple carbohydrates from supplements (r = -0.650). An ecological perspective represents more realistically the relationship between gut microbiota composition and performance compared to single-taxon approaches. The composition and periodisation of diet and supplementation during a Grand Tour, particularly carbohydrates, could be designed to modulate gut microbiota composition to allow better performance.

Duration of Zearalenone Exposure Has Implications on Health Parameters of Lactating Cows.

There is a limited research focus on evaluating the detrimental effects of prolonged zearalenone (ZEN) intake on dairy cows' health under controlled conditions. This experiment was conducted to evaluate whether the length of exposure to a ZEN-contaminated total mixed ration (TMR) at a level of 9.45 mg per day can negatively influence animal health parameters, such as milk composition, rumen and fecal fermentation, and the chewing activity of lactating dairy cows. For this experiment, we used 18 lactating Simmental cows that were fed a diet of 60% forage and 40% concentrate (on dry matter basis) for 26 consecutive days. The first 4 days were for adaptation prior to the first sampling day (day 0). The sampling events took place on day 0 (baseline) without ZEN, followed by day 1, day 7, day 14, and day 21 (with toxin). Dry matter intake (DMI) and ruminating chews per minute increased on the third week of ZEN inclusion; meanwhile, ruminating, eating, and drinking times were not affected. Most milk composition variables were also unaffected. Rumen fluid osmolality increased on day 21 and total short-chain fatty acids (SCFA) of ruminal fluid decreased on day 7. Fecal SCFA increased on day 21 and the acetate-to-propionate ratio increased from day 1 onwards, showing the influence of toxin intake. Animal health parameters, like heart rate, respiratory rate, and body temperature, were negatively influenced by ZEN intake, all increasing consistently on days 4 and 6, 9 and 12, and 16 and 18, respectively. The liver enzyme glutamate dehydrogenase decreased in response to ZEN intake on day 7. A total daily ZEN intake at the level of 9.45 mg did not show detrimental effects on DMI. Nevertheless, certain health parameters were negatively affected, including body temperature, respiratory rate, and heart rate, starting from the 7th day of ZEN intake, with additional signs of possible loss of water balance on the last sampling day.

Comparison of a Daily Steviol Glycoside Beverage compared with a Sucrose Beverage for Four Weeks on Gut Microbiome in Healthy Adults

BackgroundRecent studies suggest that some nonnutritive sweeteners (NNS) have deleterious effects on the human gut microbiome (HGM). The effect of steviol glycosides on the HGM has not been well studied. ObjectiveWe aimed to evaluate the effects of stevia- compared with sucrose-sweetened beverages on the HGM and fecal short-chain fatty acid (SCFA) profiles. MethodsUsing a randomized, double-blinded, parallel-design study, n = 59 healthy adults [female/male, n = 36/23, aged 31±9 y, body mass index (BMI): 22.6±1.7 kg/m2] consumed 16 oz of a beverage containing either 25% of the acceptable daily intake (ADI) of stevia or 30 g of sucrose daily for 4 weeks followed by a 4-week washout. At weeks 0 (baseline), 4, and 8, the HGM was characterized via shotgun sequencing, fecal SCFA concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry and anthropometric measurements, fasting serum glucose, insulin and lipids, blood pressure, pulse, and 3-d diet records were obtained. ResultsThere were no significant differences in the HGM or fecal SCFA between the stevia and sucrose groups at baseline (P > 0.05). At week 4 (after intervention), there were no significant differences in the HGM at the phylum, family, genus, or species level between the stevia and sucrose groups and no significant differences in fecal SCFA. At week 4, BMI had increased by 0.3 kg/m2 (P = 0.013) in sucrose compared with stevia, but all other anthropometric and cardiometabolic measures and food intake did not differ significantly (P > 0.05). At week 8 (after washout), there were no significant differences in the HGM, fecal SFCA, or any anthropometric or cardiometabolic measure between the stevia and sucrose groups (P > 0.05). ConclusionsDaily consumption of a beverage sweetened with 25% of the ADI of stevia for 4 weeks had no significant effects on the HGM, fecal SCFA, or fasting cardiometabolic measures, compared with daily consumption of a beverage sweetened with 30 g of sucrose. Trial registrationclinicaltrials.gov as NCT05264636

A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids.

Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study's hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26nmol/g and 4.13nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota.

Comparative Study of the Effects of Dietary-Free and -Bound Nε-Carboxymethyllysine on Gut Microbiota and Intestinal Barrier.

Nε-carboxymethyllysine (CML) is produced by a nonenzymatic reaction between reducing sugar and ε-amino group of lysine in food and exists as free and bound forms with varying digestibility and absorption properties in vivo, causing diverse interactions with gut microbiota. The effects of different forms of dietary CML on the gut microbiota and intestinal barrier of mice were explored. Mice were exposed to free and bound CML for 12 weeks, and colonic morphology, gut microbiota, fecal short-chain fatty acids (SCFAs), intestinal barrier, and receptor for AGE (RAGE) signaling cascades were measured. The results indicated that dietary-free CML increased the relative abundance of SCFA-producing genera including Blautia, Faecalibacterium, Agathobacter, and Roseburia. In contrast, dietary-bound CML mainly increased the relative abundance of Akkermansia. Moreover, dietary-free and -bound CML promoted the gene and protein expression of zonula occludens-1 and claudin-1. Additionally, the intake of free and bound CML caused an upregulation of RAGE expression but did not activate downstream inflammatory pathways due to the upregulation of oligosaccharyl transferase complex protein 48 (AGER1) expression, indicating a delicate balance between protective and proinflammatory effects in vivo. Dietary-free and -bound CML could modulate the gut microbiota community and increase tight-junction expression, and dietary-free CML might exert a higher potential benefit on gut microbiota and SCFAs than dietary-bound CML.

Aspartame Intake Delayed Puberty Onset in Female Offspring Rats and Girls.

The disturbance of the hypothalamic-pituitary-gonadal (HPG) axis, gut microbiota (GM) community, and short-chain fatty acids (SCFAs) is a triggering factor for pubertal onset. The study investigates the effects of the long-term intake of aspartame on puberty and GM in animals and humans. Aspartame-fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60mgkg-1 aspartame treatment decreases the mRNA levels of gonadotropin-releasing hormone (GnRH), Kiss1, and G protein-coupled receptor 54 (GPR54), increases the mRNA level of RFamide-related peptide-3 (RFRP-3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60mgkg-1 aspartame treatment. Among which, Escherichia-Shigella is negatively correlated with several SCFAs. In girls, high-dose aspartame consumption decreases the risk of precocious puberty. Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60mgkg-1 aspartame-fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP-3. An acceptable dose of aspartame should be recommended during childhood.