Concentrations Of Short-chain Fatty Acids Research Articles

Role of liraglutide on cardiotoxicity and gut microbiota changes induced by doxorubicin in rats

Abstract Background Cancer is one of the main causes of morbidity and mortality worldwide. Despite doxorubicin (DOX) being an effective chemotherapy drug, DOX-induced cardiotoxicity is the most severe side effect, limiting its use. There is no effective treatment for preventing DOX-induced cardiotoxicity. Gut microbiota seems to have a role in cardiovascular disease. Glucagon like peptide-1 (GLP-1) analogs such as liraglutide have shown benefits in cardiovascular diseases and seem to affect gut microbiota. Purpose To evaluate the role of liraglutide in modulating acute DOX-induced cardiotoxicity and gut microbiota. Methods Sixty male Wistar rats were allocated into four groups: Control (C), DOX (D), Liraglutide (L), and DOX + Liraglutide (DL). Animals in L and DL groups received a subcutaneous injection of 0.6 mg/kg liraglutide daily for 2 weeks. After 12 days, D and DL groups received an intraperitoneal injection of DOX (20 mg/kg). Rats were subjected to echocardiogram and isolated heart functional study 48 hours after DOX injection. At the end of the experiment, feces were collected to evaluate microbiota and short chain fatty acid concentration. Statistical analyses: Generalized linear model (GLM), ANCOVA and PERMANOVA (p<0.05). Results DOX-treated rats had worse cardiac function than rats that did not receive DOX in both echocardiography and isolated heart study; liraglutide did not change any functional parameters (Table). In feces, the phylum Bacteroidota was reduced in D and L groups compared to C and the phylum Pseudomonadota was increased in D and DL compared to C and L. Alpha-diversity did not differ between groups. Beta-diversity differed between C, D and L groups, and was similar between D and DL (Figure). Feces short chain fatty acid concentration was reduced in DOX-treated rats, with no effect from liraglutide (Figure). Conclusion DOX altered the function and composition of gut microbiota and caused acute cardiotoxicity; liraglutide changed gut microbiota and did not improve cardiac function.Table.Left ventricular functional dataFigure.Microbiota

Gut microbiota predict retinopathy in patients with diabetes: A longitudinal cohort study

The gut microbiota has emerged as an independent risk factor for diabetes and its complications. This research aimed to delve into the intricate relationship between the gut microbiome and diabetic retinopathy (DR) through a dual approach of cross-sectional and prospective cohort studies. In our cross-sectional study cross-sectional investigation involving ninety-nine individuals with diabetes, distinct microbial signatures associated with DR were identified. Specifically, gut microbiome profiling revealed decreased levels of Butyricicoccus and Ruminococcus torques group, alongside upregulated methanogenesis pathways among DR patients. These individuals concurrently exhibited lower concentrations of short-chain fatty acids in their plasma. Leveraging machine learning models, including random forest classifiers, we constructed a panel of microbial genera and genes that robustly differentiated DR cases. Importantly, these genera also demonstrated significant correlations with dietary patterns and the molecular profiles of peripheral blood mononuclear cells. Building upon these findings, our prospective cohort study followed 62 diabetes patients over a 2-year period to assess the predictive value of these microbial markers. The results underlined the panel’s efficacy in predicting DR incidence. By stratifying patients based on the predictive genera and metabolites identified in the cross-sectional phase, we established significant associations between reduced levels of Butyricicoccus, plasma acetate, and increased susceptibility to DR. This investigation not only deepens our understanding of how gut microbiota influences DR but also underscores the potential of microbial markers as early indicators of disease risk. These insights hold promise for developing targeted interventions aimed at mitigating the impact of diabetic complications.Key points• Microbial signatures are differed in diabetic patients with and without retinopathy• DR-related taxa are linked to dietary habits and transcriptomic profiles• Lower abundances of Butyricicoccus and acetate were prospectively associated with DR

Dietary Pleurotus citrinopileatus Polysaccharide Improves Growth Performance and Meat Quality Associated with Alterations of Gut Microbiota in Arbor Acre Broilers

Adding edible fungal polysaccharides to animal diets improves growth performance, meat quality, intestinal health, and immunity without adverse effects. This study aimed to evaluate the impact of Pleurotus citrinopileatus polysaccharide (PCP, including PCP250, PCP500, PCP750, and PCP1000 mg/kg) on the growth performance, meat quality, and microbial composition of Arbor Acre (AA) broilers (total 180) by metabolomics and high-throughput sequencing. The results showed that adding PCP enhanced chicken meat tenderness, redness (a*), and water retention and raised essential amino acids and flavor amino acids (such as umami and sweet amino acids) content. The metabolomics revealed that IMP, creatine, betaine, sarcosine, and taurine were related to improving meat quality in broilers by PCP addition. In addition, amino acid, purine, and lipid metabolism were the main metabolic pathways. Moreover, PCP could regulate muscle metabolism by increasing the relative abundance of Lachnospiraceae and Lactobacillus and the content of short-chain fatty acids (SCFAs). Therefore, PCP may become a promising new dietary supplement in the future, which may improve the yield and quality of broiler chickens.

Effectiveness and safety study of formula containing probiotics, prebiotics, synbiotics on fullterm infants' growth - a systematic review and meta-analysis of randomized controlled study.

Probiotics, prebiotics, and synbiotics, are hot topics of research and have been shown to improve the body's disease state and promote health. Analysis of whether infant formula containing probiotcs, prebiotics, synbiotics is beneficial to infant and child growth. We systematically searched multiple electronic databases (PubMed, Web of Science, The Cochrane Library, Embase) to identify eligible studies published from 1966 to December 25, 2022. Included studies were randomized controlled trials (RCTs) studying the influence of milk powder containing probiotcs, prebiotics, synbiotics on infants and children's growth. RevMan 5.4 was used to analyze the data. A total of 55 RCTs with a total sample size of 8868 participants met the inclusion criteria. Milk powder with probiotics, prebiotics, synbiotics does not significantly improve the growth of infants and children (Weight, height, BMI, and Head Circumference); The incidence of minor adverse events (OR 0.88, 95% CI 0.70-1.11 P = 0.28) and serious adverse events (OR 0.92, 95% CI 0.62-1.36 P = 0.67) was also comparable to the control group; The intestinal microbial diversity of infants consuming probiotcs, prebiotics, synbiotics supplemented formula was lower than that of infants consuming formula without probiotcs, prebiotics, synbiotics (SMD -0.88, 95% CI -1.66- -0.1 P = 0.03), but the abundance of individual beneficial flora was increased. (SMD 1.62, 95%CI 0.61-2.62 P = 0.002). In particular, the abundance of Lactobacillus (SMD 1.62, 95% CI 0.61-2.62 P = 0.002). For metabolites, synbiotics increased fecal antibody concentrations (SMD 0.47, 95% CI 0.08-0.86 P = 0.02), but fecal short-chain fatty acid concentrations remained balanced in both groups (SMD 0.05 95% CI -0.17-0.28 P = 0.64). Compared to the control group, infants who consumed formula with prebiotics had softer stools (SMD -1.47, 95% CI -2.23 to -0.7 P = 0.002) and lower stool pH (SMD -0.82, 95% CI -1.15- -0.5 P < 0.00001), there is also more frequency of bowel movements (SMD 0.27, 95% CI 0.09-0.44 P = 0.002). Probiotcs, prebiotics, synbiotics supplemented formulas significantly increased abundance of individual probiotics, alter intestinal antibody secretion, and improve bowel movements. Incidence of adverse reactions did not differ between the two groups. So we can choose formula-supplemented probiotcs, prebiotics, synbiotics to maintain the intestinal health of infants.

Preventive effects of matrine on LPS-induced inflammation in RAW 264.7 cells and intestinal damage in mice through the TLR4/NF-κB/MAPK pathway

BackgroundMatrine is a tetracyclic quinolizidine alkaloid with diverse bioactive properties, including anti-inflammatory and neuroprotective properties. However, the underlying anti-inflammatory mechanisms remain unclear. PurposeThis study aimed to explore how matrine reduces Lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells and to assess its protective effects against LPS-induced intestinal damage. MethodsThe effect of matrine on cell viability was assessed using the cell counting kit-8 (CCK-8) assay. Additionally, its impact on inflammatory cytokines and macrophage polarization was assessed using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. The effects on intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), nitric oxide (NO) production, and oxidative stress were evaluated using 2′,7′-dichlorodihydrofluorescein diacetate staining and JC-1 and Griess assays. Immunofluorescence staining was used to observe the translocation of the NF-κB p65 subunit. Western blotting (WB) and qRT-PCR were employed to analyze the expression levels of proteins related to the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. An LPS-induced mouse model was established to study the intestinal inflammation and barrier injury. Mouse feces characteristics, colon length, and disease activity index (DAI) were recorded. Hematoxylin-eosin (H&E) and alcian blue/periodic acid schiff (AB/PAS) staining were used to observe morphological changes and barrier damage in the duodenum, jejunum, ileum, and colon and to measure villus length, crypt depth, goblet cell count, and positive areas in the duodenum, jejunum, and ileum. The content of short-chain fatty acids (SCFAs) in the colon was determined using gas chromatography (GC). ResultsMatrine inhibited LPS-induced inflammatory cytokine levels, suppressed macrophage M1 polarization, and promoted M2 macrophage polarization. Matrine reduced LPS-induced increases in ROS and NO levels and regulates oxidative stress. Additionally, matrine inhibited the nuclear translocation of the NF-κB p65 subunit and exerted anti-inflammatory effects by suppressing the activation of the TLR4/NF-κB/MAPK pathway. In vivo experiments indicated that matrine significantly alleviated LPS-induced diarrhea, increased DAI, and shortened the colon. Matrine reduced the production of the pro-inflammatory cytokine interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α and the pro-inflammatory mediator NO in mouse intestinal tissues while promoting the content of the anti-inflammatory cytokine IL-10. Furthermore, it improved intestinal tissue structure and alleviated LPS-induced intestinal barrier damage. Finally, matrine increased the SCFA levels in the intestine. ConclusionMatrine exerted its anti-inflammatory effects and protects against intestinal injury through the TLR4/NF-κB/MAPK signaling pathway.

High-fat diet promotes type 2 diabetes mellitus by disrupting gut microbial rhythms and short-chain fatty acid synthesis.

Diabetes ranks among the top 10 causes of death globally, with over 90% of individuals diagnosed with diabetes having type 2 diabetes mellitus (T2DM). It is acknowledged that a high-fat diet (HFD) poses a serious risk for T2DM. The imbalance of intestinal flora, mediated by HFD, can potentially exacerbate the onset and progression of T2DM. However, the impact of HFD on pathological indicators and the intestinal microbiome in the development of T2DM has not been systematically investigated. Therefore, a HFD mouse model and a T2DM mouse model were established, respectively, in this study. The role of HFD as a driving factor in the development of T2DM was assessed using various measures, including basic pathological indicators of T2DM, lipid metabolism, liver oxidative stress, intestinal permeability, levels of inflammatory factors, gut microbiota, and short-chain fatty acids (SCFAs). The findings indicated that HFD could influence the aforementioned measures to align with T2DM changes, but the contribution of HFD varied across different pathological metrics of T2DM. The impact of HFD on low-density lipoprotein cholesterol, glutathione peroxidase, malondialdehyde, and tumor necrosis factor-α did not show a statistically significant difference from those observed in T2DM during its development. In addition, regarding gut microbes, HFD primarily influenced the alterations in bacteria capable of synthesizing SCFAs. The notable decrease in SCFA content in both serum and cecal matter further underscored the effect of HFD on SCFA-synthesising bacteria in mice. Hence, this research provided a systematic assessment of HFD's propelling role in T2DM's progression. It was inferred that gut microbes, particularly those capable of synthesizing SCFAs, could serve as potential targets for the future prevention and treatment of T2DM instigated by HFD.

Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.

Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS). Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments. The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis. These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.

Comprehensive evaluation of Flammulina velutipes residues polysaccharide based on in vitro digestion and human fecal fermentation

Flammulina velutipes residues (FVR) are the waste culture medium derived from the collection of Flammulina velutipes fruiting bodies, with an annual output that remains largely unexplored. The characteristics of digestion and fermentation of Flammulina velutipes residues polysaccharide (FVRP) are still relatively unknown. This study investigated the structure of the gut microbiota through 16 s rDNA gene sequencing and analyzed changes in short-chain fatty acid (SCFA) content via targeted metabolome analysis. The aim was to explore the prebiotic activity of FVRP based on a simulated digestion model combined with an in vitro anaerobic fermentation model. The results demonstrated that FVRP did not exhibit significant changes during in vitro digestion and fermentation but did enhance antioxidant activity. Furthermore, FVRP was found to rapidly reduce the pH value and increase SCFA production in the fermentation broth from lactic acid bacteria and human feces. Notably, FVRP altered the gut microbiota structure, significantly increasing the relative abundance of Firmicutes and Bacteroidota. Thus, FVRP could be considered a promising prebiotic food and feed additive that promotes the generation of short-chain fatty acids by modulating gut microbiota.

Moderate-intensity continuous training and high-intensity interval training alleviate glycolipid metabolism through modulation of gut microbiota and their metabolite SCFAs in diabetic rats

Glucose and lipid metabolism disorders are typical of diabetic patients and are important factors leading to macrovascular and microvascular complications. The aim of this study was to understand the effects of different exercises on glycolipid metabolism in diabetic rats and the role of gut flora in metabolic maintenance. We measured glycolipid metabolic indices and short-chain fatty acids (SCFAs) content and sequenced and analyzed gut microbes after 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) programs in type 2 diabetic rats(T2DM). We found that Enterococcaceae, Enterococcus, Subdoligranulum, Kurthia, Bacillales, and Planococcaceae may be key bacterial taxa related to T2DM and that both programs of exercise regulated the intestinal flora of rats with T2DM, improved their glycolipid metabolism, increased the abundance of SCFA-producing intestinal bacteria, and it was found that the PWY-5676 and P163-PWY pathways which are closely related to production of SCFAs were significantly upregulated in the exercise groups. Notably, MICT appeared to be more effective than HIIT in increasing the homogeneity of rat intestinal flora, enriching species, and increasing acetic acid and butyric acid content. These results suggest that exercise improves glycolipid metabolism in diabetic rats, which may be attributed to alterations in the structure of their intestinal flora.

Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection-

ABSTRACT Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786–0.934], p < .0001).

GC-MS quantification of fecal short-chain fatty acids and spectrophotometric detection of indole: Do rectal swabs produce comparable results as stool samples? - A pilot study.

The exploration of the gut microbiome and related metabolites holds an exciting future in health science. The challenges associated with fecal sample testing are proper sample collection, sterile transportation, optimal transport conditions, and processing as all these factors could potentially change the microbiome composition, further exacerbated by the patient's customary discomfort regarding feces samples. The study aimed to compare the usage of rectal swabs and stool samples for short-chain fatty acid estimation using gas chromatography-mass spectrometry (GC-MS) and indole estimation using spectrophotometry. From May 2022 to June 2022, three women were recruited from the Department of Obstetrics and Gynecology (OBG) in a secondary care hospital in coastal Karnataka. During their clinical visit, a rectal swab was collected, and the stool sample was transported to the hospital from the patient's home in sterile containers provided. After the extraction, short-chain fatty acids (acetate, propionate, and butyrate) were quantified using GC-MS. The fecal indole concentration was determined using a hydroxylamine-based assay. The GC-MS analysis failed to detect the concentrations of short-chain fatty acids in rectal swab samples. Indole concentrations in stool and swab samples were significantly different. The study's findings do not support the use of rectal swabs to analyze gut metabolites.

Effects of Trace Mineral Source on Growth Performance, Antioxidant Activity, and Meat Quality of Pigs Fed an Oxidized Soy Oil Supplemented Diet.

This study investigates the effects of oil quality and trace mineral source on the growth performance, antioxidant activity, and meat quality of growing-finishing pigs. A total of 180 crossbred pigs (Duroc × Landrace × Large White [64.4 ± 1.95]) were randomly allocated five dietary treatments based on body weight (BW) and sex in a 30 d trial. Pigs were fed five diets: (i) fresh soy oil + inorganic trace minerals (ITMs) + inorganic selenium (FISI), (ii) oxidized soy oil + ITMs + inorganic selenium (OISI), (iii) fresh soy oil + ITMs + selenium yeast (FISY), (iv) oxidized soy oil + ITMs + selenium yeast (OISY), and (v) oxidized soy oil + organic trace minerals (OTMs) + selenium yeast (OOSY). Each dietary treatment included six replicates and six pigs per replicate (three barrows and three gilts). Feeding OISI resulted in lower average daily gain (ADG) and dressing percentage (p < 0.05). The OOSY group had a higher dressing percentage and activities of serum CAT and GSH-Px in growing-finishing pigs (p < 0.05). In addition, the relative abundance of Campylobacterota in the colonic digesta varied with the quality of soy oil and source of trace minerals (p < 0.05), but no significant differences in short-chain fatty acid concentrations were observed among all dietary groups. In conclusion, adding oxidized soy oil to the diet negatively impacted the ADG and dressing percentage of growing-finishing pigs, and replacing ITMs with OTMs and SY alleviated these negative impacts. A combination of OTMs and SY can support antioxidant capacity to mitigate the negative impacts of oxidized oil on the growth performance and dressing percentage of growing-finishing pigs.

Effects of chicken slurry inclusion on apparent total tract macronutrient digestibility, palatability, and fecal characteristics, microbiota, and metabolites of healthy adult dogs.

"Premium" pet foods are often formulated with meat slurries. Meat slurries are believed to be of higher quality than rendered meals, but inadequate research has been performed to test how their inclusion affects palatability, digestibility, or indicators of gastrointestinal health. Therefore, the objectives of this study were to determine how chicken slurry inclusion affected the palatability and apparent total tract macronutrient digestibility (ATTD) of dog foods and to assess their effects on the fecal characteristics, metabolites, and microbiota of dogs. A replicated 3x3 Latin square design digestibility study was conducted using 9 healthy adult dogs (age = 5.44 ± 0.53 yr) to test diets containing 0% (control; CON), 8% (low inclusion; LOW), and 16% (high inclusion; HIGH) chicken slurry. The experiment comprised three 21-day experimental periods (14 days of adaptation, 5 days of total fecal collection (used for ATTD calculations), and 2 days of blood collection). On the first day of fecal collections, one fresh sample was collected for measurement of pH, dry matter (DM) content, fermentative metabolite concentrations, and microbiota populations. A 2-day palatability study (n=20 dogs) was also conducted to compare CON vs. HIGH. Data were analyzed statistically by Mixed Models using SAS 9.4, with P<0.05 being significant. In the palatability study, dogs were shown to prefer (P<0.05) the HIGH diet by a ratio of 2:1. In the digestibility study, fecal output, scores, pH, and DM percentage were not different among diets. The ATTD of protein was higher (P<0.05) for the HIGH diet (84.6%) than for the LOW (82.7%) or CON (82.6%) diets. The ATTD of other nutrients and energy were not different among diets (all over 80%). Fecal propionate, butyrate, and total short-chain fatty acid concentrations were higher (P<0.05) in dogs fed the LOW diet (122.0, 67.4, and 408.2 βmol/g, respectively) than those fed the HIGH diet (89.0, 46.9, and 338.2 βmol/g, respectively). The other fecal metabolites (acetate, branched-chain fatty acids, ammonia, phenol, and indole) were not different among treatments. Few changes to the fecal microbiota were noted. However, the relative abundance of fecal Fusobacterium was higher (P<0.05) in dogs fed the CON diet than those fed the HIGH diet (25.% vs. 20.0% relative abundance). In summary, chicken slurry inclusion improved palatability but had minimal effects on nutrient digestibility and fecal characteristics, metabolites, and microbiota.

ROS/Thermo dual-sensitive hydrogel loaded with a nanoemulsion of patchouli essential oil for ulcerative colitis

Patchouli essential oil (PEO) is acknowledged as a potent contender for the management of ulcerative colitis (UC). However, the limited ability of PEO to be absorbed by the body and its low stability substantially limit its potential uses. Furthermore, UC lesions are mainly concentrated in the rectal and colonic mucosa, with excessive production of reactive oxygen species (ROS). Herein, a nanoemulsion of PEO (PEONE) was developed to enhance the stability and bioavailability of a drug. Subsequently, we developed a novel platform for the rectal administration of a ROS/thermo dual-sensitive Bletilla striata polysaccharide-based hydrogel (RTH) co-loaded with PEONE to efficiently treat UC. As expected, the sol–gel transition of PEONE@RTH, after its intrarectal administration, resulted in its extended presence in the colon and facilitated its attachment to the inflammation site. Moreover, PEONE@RTH alleviated dextran sulfate sodium-induced UC symptoms by suppressing inflammation and oxidative stress, repairing the damage to the intestinal epithelial barrier (claudin-1 and occludin), increasing short-chain fatty acid content and inhibiting the MAPK signalling pathway. Additionally, PEONE@RTH exhibits exceptional safety and biocompatibility. Thus, PEONE@RTH has the potential to provide a novel approach for treating UC and other intestinal disorders characterised by similar clinical conditions.

Effects of Chitosan-Based Additive on Rumen Fermentation and Microbial Community, Nutrients Digestibility and Lactation Performance in Goats.

Recently, the potential of using chitosan (CHI) as a feed additive to enhance ruminal fermentation and improve animal performance has gained increasing attention in ruminant nutrition. This study was undertaken to investigate the effect of dietary supplementation with increasing doses of CHI on rumen fermentation attributes and microbial composition, digestibility and milk performance in Dhofari goats. Twenty-four lactating goats (27 ± 1.8 kg of initial live body weight) were fed a control diet comprising of Rhodes grass hay plus a concentrate feed mixture. Goats were assigned to one of three experimental treatments (n = 8 per treatment) as: (1) control diet with no supplement (CTRL), (2) control diet with 0.300 g/day CHI (CHI0.3) and (3) control diet supplemented with 0.600 g/day CHI (CHI0.6) for a 45-day experimental period. Dietary supplementation with increasing doses of CHI decreased (p < 0.05) linearly ruminal pH (p = 0.023), total short chain fatty acids concentrations (p = 0.011), acetate (p = 0.013) and butyrate (p = 0.042) proportions, acetate to propionate ratio (p < 0.001), estimated methane (CH4) production (p < 0.001), ammonia nitrogen concentrations (p = 0.003) and protozoa abundance (p = 0.003). However, the ruminal propionate proportion augmented (p = 0.002) linearly with increasing doses of CHI in the diet. Increasing doses of CHI linearly increased the abundance of the ruminal propionate-producing bacteria, while diminished acetate and CH4-producing bacteria (p < 0.05). Serum total protein (p = 0.037) and glucose (p = 0.042) levels linearly increased as CHI doses increased in the diet. However, serum UREA levels decreased linearly (p = 0.002) by 21% with increasing CHI amounts in the diet. The digestibility of organic matter, crude protein and neutral detergent fibre increased linearly with the increasing CHI doses (p < 0.05). Neither linear nor quadratic responses (p > 0.05) were observed in daily milk yield and feed efficiency by supplementing the diet with CHI. In conclusion, supplementing the diet with CHI at a dose of 0.600 g/day as a feed additive for dairy goats reduced estimated CH4 generation and improved fibre and protein digestion, with no influence on feed intake, milk yield or composition.

Adding red propolis to the diet of Lacaune lambs: Effects on animal health, ruminal environment, performance, and meat quality

This study determined the influence of red propolis ethanolic extract in lambs' diets on the ruminal environment, animal health, and growth. Two experiments were carried out to achieve these objectives. Pilot study: Twenty-four female Lacaune lambs were divided into four groups, with three replicates and two animals per replicate (pen): T0 (Control), TP1.3, TP2.7, and TP5.3, representing 0, 1.3, 2.7, and 5.3 mL of propolis extract per animal/day, respectively. The highest daily weight gain was observed in lambs that consumed 2.7 mL of propolis extract per day, and they also had the lowest feed conversion rate compared to the control. Lower total leukocyte counts were observed in lambs that consumed propolis extract compared to control due to lower granulocyte and lymphocyte counts. Ceruloplasmin and C-reactive protein levels were lower in the serum of lambs that consumed propolis compared to the control. Lambs that consumed 1.3 and 2.7 mL of propolis extract had lower TBARS levels than the control. The effect of treatment was observed for ruminal pH, which was higher in lambs that consumed propolis extract than in control. A lower concentration of short-chain fatty acids was observed in lambs that consumed propolis than the control due to lower concentrations of acetic and butyric acid. In experiment II, 36 male Lacaune lambs were selected and divided into two groups: MONENSIN (23.45 ppm of monensin per kg/dry matter (DM)) and PROPOLIS (3.8 mL of propolis per animal/day). The animals that consumed propolis extract had greater body weight, weight gain, and average daily gain. These also had a shorter time to reduce methylene blue, thus demonstrating more significant bacterial activity in the rumen. Furthermore, they had lower counts of Escherichia coli, total coliforms, and Enterobacteria. The meat's fatty acid profile in animals fed the red propolis extract showed higher concentrations of monounsaturated fatty acids. In conclusion, adding red propolis extract to the concentrate increased weight gain, average daily gain, and oxidative balance with an antimicrobial and anti-inflammatory effect.

Potential Anti-Obesity Effect of Hazel Leaf Extract in Mice and Network Pharmacology of Selected Polyphenols

Background: Obesity is gradually becoming a widespread health problem, and treatment using natural compounds has seen an increasing trend. As a by-product of hazelnut, hazel leaf is usually disposed of as waste, but it is widely used in traditional and folk medicines around the world. Aim of this study: Based on previous studies, the effects of the regulation of lipid metabolism and the mechanism of hazel leaf polyphenol extraction obesity were investigated. Methods: In this study, a high-fat diet-fed mouse model of obesity and 3T3-L1 preadipocytes were established. The ameliorative effects of the hazel leaf polyphenol extract on obesity and the regulating lipid metabolisms were explored based on network pharmacology, gut microbiota, and molecular docking. Results: Network pharmacology showed that hazel leaf polyphenols may play a role by targeting key targets, including PPARγ, and regulating the PPAR signaling pathway. They significantly improved body weight gain, the liver index, and adiposity and lipid levels; regulated the gut microbiota and short-chain fatty acid contents; down-regulated the expression of lipid synthesis proteins SREBP1c, PPARγ, and C/EBP-α; and up-regulated the expression of p-AMPK in obese mice. They inhibited the differentiation of 3T3-L1 cells, and the expression of related proteins is consistent with the results in vivo. The molecular docking results indicated that gallic acid, quercetin-3-O-beta-D-glucopyranoside, quercetin, myricetin, and luteolin-7-O-glucoside in the hazel leaf polyphenol extract had strong binding activities with PPARγ, C/EBP-α, and AMPK. Conclusions: The results demonstrate that the hazel leaf polyphenol extract can improve obesity by regulating lipid metabolism, which provides a valuable basis for developing health products made from hazel leaf polyphenols in the future.

Development of an infant colon simulating in vitro model, I-TIM-2, to study the effects of modulation strategies on the infant gut microbiome composition and function.

The early life stages are critical for the development of the gut microbiome. Variables such as antibiotics exposure, birth-mode via Cesarean section, and formula feeding are associated with disruptions in microbiome development and are related to adverse health effects later in life. Studying the effects of microbiome-modulating strategies in infants is challenged by appropriate ethical constraints. Therefore, we developed I-TIM-2, an infant in vitro colonic model based on the validated, computer-controlled, dynamic model of the colon, TIM-2. The system, consisting of four separate compartments, was inoculated with feces from four healthy, primarily breastfed infants, displaying distinctive microbiome profiles. For each infant's fecal sample, a 96-h experiment was performed, with two compartments receiving an infant diet adapted medium and two compartments additionally receiving five human milk oligosaccharides (HMOs) in physiological concentrations and proportions. Bacterial composition was determined by shotgun metagenomics and qPCR. Concentrations of short-chain fatty acids (SCFAs) and HMOs were determined by LC-MS. Microbial diversity and high amounts of inoculum-derived species were preserved in the model throughout each experiment. Microbiome composition and SCFA concentrations were consistent with published data from infants. HMOs strongly modulated the microbiome composition by stimulating relative proportions of Bifidobacterium. This affected the metabolic output and resulted in an increased production of acetic and formic acid, characteristic of bifidobacterial HMO metabolism. In conclusion, these data demonstrate the development of a valid model to study the dynamics and modulations of the infant gut microbiome and metabolome.IMPORTANCEThe infant gut microbiome is intricately linked to the health of its host. This is partly mediated through the bacterial production of metabolites that interact with the host cells. Human milk shapes the establishment of the infant gut microbiome as it contains human milk sugars that select for primarily bifidobacteria. The establishment can be disrupted by modern interventions such as formula feeding. This can alter the microbiome composition and metabolite production profile, which can affect the host. In this article, we set up an infant in vitro colonic model to study microbiome interactions and functions. In this model, we investigated the effects of human milk sugars and their promotion of bifidobacteria at the expense of other bacteria. The model is an ideal system to assess the effects of various modulating strategies on the infant gut microbiome and its interactions with its host.

Examining the complex Interplay between gut microbiota abundance and short-chain fatty acid production in amyotrophic lateral sclerosis patients shortly after onset of disease.

This study aimed to assess differences in the enteral microbiome of relatively recent-onset amyotrophic lateral sclerosis (ALS) patients (< 6-15 months since symptom onset) compared to healthy individuals, focusing on short-chain fatty acids (SCFAs) as potential mediators of host metabolism. We included 28 volunteers (16 ALS, 12 controls) with informed consent. No significant effect of ALS on alpha diversity (measuring the variety and abundance of species within a single sample, and indicating the health and complexity of the microbiome) was observed, but ALS patients had higher abundances of Fusobacteria and Acidobacteria. ALS subtypes influenced specific species, with increased Fusobacteria and Tenericutes in spinal ALS compared to bulbar ALS. ALS patients showed increased Enterobacter, Clostridium, Veillonella, Dialister, Turicibacter, and Acidaminococcus species and decreased Prevotella, Lactobacillus, and Butyricimonas. Correlations between species varied between ALS patients and healthy individuals and among ALS subtypes. No significant differences in SCFA concentrations were found, but spinal ALS samples showed a trend towards decreased propionate content. Relationships between SCFAs and phyla colonization differed by disease status. This study suggests distinct enteral microbiome characteristics in ALS patients, though the implications are unclear. Further research is needed to determine if these differences are causative or consequential and to explore their potential as diagnostic or therapeutic targets. The study also underscores the heterogeneity of microbiome constraints in ALS and the need for more research into ALS and SCFA metabolism.

Investigating the mechanism of enhanced medicinal effects of Terminalia chebula fruit after processing based on intestinal flora and metabolomics

Background and objectiveTerminalia chebula is a classical medicine for the treatment of lingering dysentery, and both raw and processed T. chebula can alleviate ulcerative colitis (UC). The therapeutic efficacy of T. chebula is enhanced after processing, but the mechanism that processing improves this efficacy is still unknown. We investigated the medicinal effects of raw and processed T. chebula on dextran sulfate sodium (DSS)-induced UC model rats using intestinal flora and metabolomics analyses, in order to elucidate the mechanism by which processing enhances the therapeutic effect. MethodsThe major constituents of raw and processed T. chebula were detected by high-performance liquid chromatography (HPLC). UC model was replicated using the DSS method, and then UC rats were administered raw and processed T. chebula. The general physical signs, disease activity index (DAI) scores, colon histopathological morphology, and the expressions of inflammatory cytokines were used to evaluate the therapeutic effect of T. chebula. In addition, 16 s rRNA sequencing and gas chromatography-mass spectrometry (GC–MS) were used to characterize the intestinal flora and contents of short-chain fatty acids (SCFAs). Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to identify the nontargeted fecal metabolites. ResultsRaw and processed T. chebula significantly improved the general physical signs and colon inflammatory symptoms and decreased DAI scores of UC rats. Both raw and processed T. chebula mitigated intestinal flora disorders in UC rats, increasing probiotic bacteria, including Lactobacillus and Romboutsia. However, the effect of processed T. chebula was more pronounced. Moreover, the levels of SCFAs of DSS-induced UC rats were restored after drug administration, and the processed T. chebula had a better regulatory effect than raw T. chebula. In the fecal nontargeted metabolomics analysis, differential metabolites such as lipids and amino acids were identified. The processed T. chebula can regulate purine metabolism and other pathways to improve UC, and the levels of the disordered metabolites gradually approached those of the control group. ConclusionRaw and processed T. chebula had the capacity to mitigate DSS-induced UC by rebalancing the intestinal flora, restoring the contents of SCFAs, and regulating fecal metabolites, while processed T. chebula showed preferable effects.