Volatile 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

Effects of saccharomyces cerevisiae fermentation products on growth performance, fecal short chain fatty acids, and microbiota of pre-weaning calves.

This research aims to explore the effects of incorporating saccharomyces cerevisiae fermentation products (SCFP) on growth performance, nutrient digestibility, antioxidant capacity, fecal SCFAs, and microbial composition of pre-weaning calves. Twenty Holstein calves, 10 days old and weighing an average of 48.63±0.91 kg, were randomly assigned to either the control group (CON) or the SCFP group, with 10 calves in each group. The CON group received only a basal diet, while the SCFP group received the starter diet supplemented with 5 g/head/d of SCFP products (NutriTek, Diamond V Cedar Rapids, IA 52404, United States). The pre-trial period lasted for 5 days, followed by a main experimental period of 45 days. The SCFP group had significantly higher final weight, ADG, and FE compared to the control group (p < 0.05). Moreover, the SCFP group exhibited increased apparent digestibility of DM, CP, EE, ADF, Ca, and P (p < 0.05). Additionally, supplementation with SCFP led to elevated content of GH, IGF-1, and GLP-1 in serum. The inclusion of SCFP also raised serum CAT content and reduced serum MDA content in pre-weaning calves. Furthermore, SCFP supplementation influenced the composition of intestinal microflora by decreasing Actinobacteriota abundance and increasing the abundance of Ruminococcus, Lachnospiraceae_AC2044_group, Parabacteroides, and Butyricimonas. The addition of SCFP has a positive impact on the growth performance, nutrient digestibility, antioxidant capacity, and intestinal microflora composition of pre-weaning calves.

Milk-derived extracellular vehicles alleviate heart failure with preserved ejection fraction by modulating gut microbiota

Abstract Background Accounting for around 50% of human heart failure, heart failure with preserved ejection fraction (HFpEF) is driven by complex and heterogeneous pathological factors, including gut microbiome dysbiosis. We have previously reported that milk-derived extracellular vesicles (mEVs) modulate the gut microbiota in inflammatory bowel disease. However, whether mEVs can affect gut microbiota and thereby alleviate HFpEF remains unexplored. Aims We aim to uncover potential therapeutic effects of mEVs on HFpEF and if so, the underlying mechanisms. Methods The HFpEF mouse model was generated by feeding C57/B6 mice on a high-fat diet and L-NAME for 15 weeks. Mouse feces samples were analyzed to detect the presence of gut dysbiosis in HFpEF. Mice received bovine mEVs through oral gavage. Heart function was assessed with echocardiography. Mouse feces and plasma were collected to analyze gut microbiota and metabolomics, respectively. Results Gut microbiota was disturbed in HFpEF mice. Oral administration of mEVs effectively attenuated heart failure which was evidenced by less bodyweight gain, reduction in cardiac hypertrophy and lung weight, and improvement in cardiac function parameters such as ratios of E/A (1.8 vs. 1.5, p&amp;lt;0.05) and E/E’ (40 vs. 27, p&amp;lt;0.05). Moreover, the increase in mouse blood pressure in HFpEF was also inhibited upon treatment (SBP 130mmHg vs. 100mmHg, DBP 90mmHg vs. 75mmHg, p&amp;lt;0.05). Mechanistically, we ruled out the possibility of direct action of mEVs on the heart as orally administered mEVs were only distributed in the intestine. On the other hand, mEVs restored gut microbiota by increasing the abundance of beneficial bacteria such as Lachnospiraceae. As a result, oral administration of mEVs elevated blood levels of Lachnospiraceae metabolite, butyric acid, a type of short-chain fatty acid. To confirm the butyric acid-mediated heart-protective effects of mEVs, we administered butyric acid to HFpEF mice. Strikingly, butyric acid largely reproduced the therapeutic effects of mEVs on HFpEF. Conclusions Oral administration of mEVs restores gut microbiota dysbiosis, thereby attenuating heart failure in HFpEF. mEVs may represent a new biological therapeutic for the treatment of HFpEF.

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

Lactobacillaceae differentially impact butyrate-producing gut microbiota to drive CNS autoimmunity

ABSTRACT Background Short-chain fatty acids (SCFAs), produced by the gut microbiota, are thought to exert an anti-inflammatory effect on the host immune system. The levels of SCFAs and abundance of the microbiota that produce them are depleted in multiple sclerosis (MS), an autoimmune disease of the central nervous system (CNS). The mechanisms leading to this depletion are unknown. Using experimental autoimmune encephalomyelitis (EAE) as a model for MS, we have previously shown that gut microbiomes divergent in their abundance of specific commensal Lactobacillaceae, Limosilactobacillus reuteri (L. reuteri) and Ligilactobacillus murinus (L. murinus), differentially impact CNS autoimmunity. To determine the underlying mechanisms, we employed colonization by L. reuteri and L. murinus in disparate gut microbiome configurations in vivo and in vitro, profiling their impact on gut microbiome composition and metabolism, coupled with modulation of dietary fiber in the EAE model. Results We show that stable colonization by L. reuteri, but not L. murinus, exacerbates EAE, in conjunction with a significant remodeling of gut microbiome composition, depleting SCFA-producing microbiota, including Lachnospiraceae, Prevotellaceae, and Bifidobacterium, with a net decrease in bacterial metabolic pathways involved in butyrate production. In a minimal microbiome culture model in vitro, L. reuteri directly inhibited SCFA-producer growth and depleted butyrate. Genomic analysis of L. reuteri isolates revealed an enrichment in bacteriocins with known antimicrobial activity against SCFA-producing microbiota. Functionally, provision of excess dietary fiber, as the prebiotic substrate for SCFA production, elevated SCFA levels and abrogated the ability of L. reuteri to exacerbate EAE. Conclustions Our data highlight a potential mechanism for reduced SCFAs and their producers in MS through depletion by other members of the gut microbiome, demonstrating that interactions between microbiota can impact CNS autoimmunity in a diet-dependent manner. These data suggest that therapeutic restoration of SCFA levels in MS may require not only dietary intervention, but also modulation of the gut microbiome.

Segatella clades adopt distinct roles within a single individual’s gut

Segatella is a prevalent genus within individuals’ gut microbiomes worldwide, especially in non-Western populations. Although metagenomic assembly and genome isolation have shed light on its genetic diversity, the lack of available isolates from this genus has resulted in a limited understanding of how members’ genetic diversity translates into phenotypic diversity. Within the confines of a single gut microbiome, we have isolated 63 strains from diverse lineages of Segatella. We performed comparative analyses that exposed differences in cellular morphologies, preferences in polysaccharide utilization, yield of short-chain fatty acids, and antibiotic resistance across isolates. We further show that exposure to Segatella isolates either evokes strong or muted transcriptional responses in human intestinal epithelial cells. Our study exposes large phenotypic differences within related Segatella isolates, extending this to host-microbe interactions.

Association Between the Gut Microbiota and Alzheimer's Disease: An Update on Signaling Pathways and Translational Therapeutics.

Alzheimer's disease (AD) is a cognitive disease with high morbidity and mortality. In AD patients, the diversity of the gut microbiota is altered, which influences pathology through the gut-brain axis. Probiotic therapy alleviates pathological and psychological consequences by restoring the diversity of the gut microbial flora. This study addresses the role of altered gut microbiota in the progression of neuroinflammation, which is a major hallmark of AD. This process begins with the activation of glial cells, leading to the release of proinflammatory cytokines and the modulation of cholinergic anti-inflammatory pathways. Short-chain fatty acids, which are bacterial metabolites, provide neuroprotective effects and maintain blood‒brain barrier integrity. Furthermore, the gut microbiota stimulates oxidative stress and mitochondrial dysfunction, which promote AD progression. The signaling pathways involved in gut dysbiosis-mediated neuroinflammation-mediated promotion of AD include cGAS-STING, C/EBPβ/AEP, RAGE, TLR4 Myd88, and the NLRP3 inflammasome. Preclinical studies have shown that natural extracts such as Ganmaidazao extract, isoorentin, camelia oil, Sparassis crispa-1, and xanthocerasides improve gut health and can delay the worsening of AD. Clinical studies using probiotics such as Bifidobacterium spp., yeast beta-glucan, and drugs such as sodium oligomannate and rifaximine have shown improvements in gut health, resulting in the amelioration of AD symptoms. This study incorporates the most current research on the pathophysiology of AD involving the gut microbiota and highlights the knowledge gaps that need to be filled to develop potent therapeutics against AD.

Exploring flagellar contributions to motility and virulence in Arcobacter butzleri.

Flagella is a well-known bacterial structure crucial for motility, which also plays pivotal roles in pathogenesis. Arcobacter butzleri, an enteropathogen, possesses a distinctive polar flagellum whose functional aspects remain largely unexplored. Upon investigating the factors influencing A. butzleri motility, we uncovered that environmental conditions like temperature, oxygen levels, and nutrient availability play a significant role. Furthermore, compounds that are found in human gut, such as short-chain fatty acids, mucins and bile salts, have a role in modulating the motility, and in turn, the pathogenicity of A. butzleri. Further investigation demonstrated that A. butzleri ΔflaA mutant showed a reduction in motility with a close to null average velocity, as well as a reduction on biofilm formation. In addition, compared with the wild-type, the ΔflaA mutant showed a decreased ability to invade Caco-2 cells and to adhere to mucins. Taken together, our findings support the role of environmental conditions and gut host associated compounds influencing key physiological aspects of the gastrointestinal pathogen A. butzleri, such as motility, and support the role of the flagellum on bacterial virulence.

Determination of the Impact of Extruded Soybean Press Cake on Rearing and Health Indices of Piglets

The study was conducted to evaluate the alternative to imported soybean meal—extruded soybean press cake—in feeding weaning pigs. The experiment was carried out with 20 35-day-old weaned pigs weighing about 8.8 kg, divided into 2 groups (10 pigs in each) differing in the main protein source: group I—control, solvent-extraction soybean meal, group II— extruded soybean press cake. The feed mixtures were iso-protein and iso-energetic. After 35 days of feeding, the pigs were slaughtered. The samples of blood, intestinal tissue and digesta, meat, and back fat were collected for analyses. Replacement of soybean meal with extruded soybean press cake in the weaners’ diet had no statistically significant effect on growth performance and feed utilization. Histomorphometry analysis of the intestines did not indicate any harmful changes. The soybean press cake did not affect the sum of volatile fatty acids in the large intestine, but the ammonia concentration was lower in the distal colon (p ≤ 0.05). It was found that the extruded soybean press cake in the feed significantly affected the fatty acid profile (p ≤ 0.05) of meat and back fat, increasing the amount of PUFAs; however, no negative impact on the durability of meat and back fat during storage was noted. In conclusion, the study confirmed the possibility of completely replacing solvent-extraction soybean meal with extruded soybean press cake in the feeding of weaned pigs.

Impacts of Protein and Energy Levels on Rumen Fermentation and Microbial Activity Under Different Incubation Temperatures.

This study aimed to explore the effects of different incubation temperatures on ruminal fermentation and rumen microorganisms and determine the appropriate protein and energy levels to enhance microbial protein synthesis using an in vitro system. Rumen inoculum was collected from two fistulated Holstein heifers (trial 1: BW: 652.3 kg ± 25.2; trial 2: BW: 683.3 kg ± 30.2) and assessed using a closed-batch culture system. The experimental model employed a 2 × 5 factorial arrangement using incubation temperatures set to 39 and 41 °C, with protein levels set to 12.0, 13.5, 15.0, 16.5, and 18.0% of DM in trial 1 or with energy levels set to 2.4, 2.5, 2.6, 2.7, and 2.8 Mcal/kg of DM in trial 2. The data were analyzed using the MIXED procedure. The results showed increased (p < 0.05) NH3-N concentrations and total volatile fatty acids (TVFAs) with higher incubation temperatures, while the liquid-associated bacterial (LAB) amounts decreased (p < 0.05) in trials 1 and 2. The interaction between the energy level and incubation temperature affected (p < 0.05) the LAB protein levels in trial 2. Higher protein levels led to increased (p < 0.05) NH3-N and acetate concentrations, but it decreased (p < 0.05) the propionate percentage. Conversely, higher energy levels decreased (p < 0.05) the amount of acetate and increased the propionate concentration, altering the acetate-to-propionate ratio. However, no interaction involving TVFA and LAB was observed between the incubation temperature and the protein or energy levels. Changes in the NH3-N, TVFAs, and LAB protein amounts were observed under different incubation temperatures and energy levels. In conclusion, these findings provide insight into the metabolic adaptation under different ruminal temperatures and the impacts of dietary adjustments on rumen fermentation and microbial activity. However, there are limitations to replicating the complex physiological responses that occur within the whole body solely through in vitro experiments.

Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4

In patients with sepsis, neutrophil apoptosis tends to be inversely proportional to the severity of sepsis, but its mechanism is not yet clear. This study aimed to explore the mechanism of fatty acid binding protein 4 (FABP4) regulating neutrophil apoptosis through combined analysis of gut microbiota and short-chain fatty acids (SCFAs) metabolism. First, neutrophils from bronchoalveolar lavage fluid (BALF) of patients with sepsis-induced acute respiratory distress syndrome (ARDS) were purified and isolated RNA was applied for sequencing. Then, the cecal ligation and puncture (CLP) method was applied to induce the mouse sepsis model. After intervention with differential SCFAs sodium acetate, neutrophil apoptosis and FABP4 expression were further analyzed. Then, FABP4 inhibitor BMS309403 was used to treat neutrophils. We found CLP group had increased lung injury score, lung tissue wet/dry ratio, lung vascular permeability, and inflammatory factors IL-1β, TNF-α, IL-6, IFN-γ, and CCL3 levels in both bronchoalveolar lavage fluid and lung tissue. Additionally, FABP4 was lower in neutrophils of ARDS patients and mice. Meanwhile, CLP-induced dysbiosis of gut microbiota and changes in SCFAs levels were observed. Further verification showed that acetic acids reduced neutrophil apoptosis and FABP4 expression via FFAR2. Besides, FABP4 affected neutrophil apoptosis through endoplasmic reticulum (ER) stress, and neutrophil depletion alleviated the promotion of ARDS development by BMS309403. Moreover, FABP4 in neutrophils regulated the injury of RLE-6TN through inflammatory factors. In conclusion, FABP4 affected by gut microbiota-derived SCFAs delayed neutrophil apoptosis through ER stress, leading to increased inflammatory factors mediating lung epithelial cell damage.

The efficacy of preemptive multimodal analgesia in elderly patients undergoing laparoscopic colorectal surgery: a randomized controlled trial

Objective To evaluate the effectiveness of preemptive multimodal analgesiain elderly patients undergoing laparoscopic colorectal surgery. Methods A prospective randomized controlled study was conducted in the Department of Gastrointestinal Surgery of the Second Hospital of Hebei Medical University from January 2022 to December 2022. A total of 133 patients were included according to the criteria and randomly divided into preemptive analgesia (PRA) group (test group, 67patients) and postoperative analgesia (POA) group (control group, 66patients). Results The Visual Analog Scale (VAS)scores of PRA group 24 h, 48 h, and 72 h after operation were lower than those of POA group, and the difference was statistically significant, P < 0.001.The incidences of postoperative gastrointestinal dysfunction (POGD) and postoperative delirium (POD)in PRA group were 13.43% and 8.98%, respectively, which were significantly lower than those in POA group (31.82% and 24.24%), P < 0.05. The levels of IL-6 and IL-10 in PRA group after the operation were 17.54 ± 2.13 ng/L and 15.57 ± 1.71 ng/L respectively, which were lower than those in POA group (25.45 ± 2.95 ng/L and 23.45 ± 1.88 ng/L), P < 0.05. The level of acetylcholinesterase(AchE) was 56.34 ± 5.62 nmol/L in the POA group, which was significantly higher than that in the POA group (49.59 ± 5.52 nmol/L), P < 0.001. Conclusion Preemptive multimodal analgesia can reduce the incidence of POGD and POD in elderly patients undergoing laparoscopic gastrocolic surgery, improve the recovery process of postoperative gastrointestinal function, increase the concentrations of propionic acid and butyric acid in short chain fatty acids (SCFAs) and the number of beneficial intestinal bacteria.

The anti-obesity effects of postbiotics: A systematic review of pre-clinical and clinical studies

BackgroundThe growing prevalence of obesity has become a major concern worldwide, therefore a great number of studies are conducted every day in the field of obesity. Since postbiotics are a newly introduced term, there is not much systematic evidence about their function and impact on obesity. We designed this study to systematically review the effect of different types of postbiotics on obesity. MethodsA systematic search was conducted using PubMed, SCOPUS, and Web of Science databases up to August 2023. Both human and animal interventional studies that investigated the effects of any type of postbiotic on obesity and obesity-related factors were eligible. Screening, data extraction, and quality assessment were conducted independently by two researchers. The quality of the studies was appraised using Cochrane and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE’s) risk of bias tool. ResultsOf the 19373 retrieved studies, finally, 49 studies were included (9 human studies and 40 animal studies). Short-chain fatty acids and heat-killed (inactivated) bacteria were the most used postbiotics. In human clinical trials, inactivated Lactobacillus amylovorus (CP1563), Bifidobacterium animalis subsp. lactis (CECT 8145) and Pediococcus pentosaceus (LP28) were administered orally as postbiotics which improved body composition and anthropometric indices. Animal studies evaluated other types of postbiotics including muramyl dipeptide, cell-free extracts, urolithin A&B, extracellular Vesicles, exopolysaccharides, and surface Layer Proteins, supporting the anti-obesity effects of postbiotics. ConclusionPostbiotics seem to be a safe intervention and the results were in favor of a reduction in adipogenesis as well as an increase in energy expenditure. Further high-quality studies are required in this relatively new topic.

Effects of Edible Grass (Rumex patientia L. × Rumex tianschanicus A. LOS) Leaf Powder on Growth Performance, Antioxidant Properties, Cecal Short-Chain Fatty Acids, and Microbial Community Levels in Broilers

The hybrid plant edible grass (Rumex patientia L. × Rumex tianschanicus A. LOS), a member of the Rumex genus, presents a novel food source with a protein content of approximately 30–40%. By incorporating non-traditional feed sources, such as edible grass leaf powder (EGLP), into broiler production, costs could be reduced. The experimental subjects of this study were Arbor Acres (AA) broilers. A total of 300 newly hatched broilers were randomly divided into to five groups, with each group consisting of six cages, housing 10 birds per cage. The control group was fed a basal diet composed of maize and soybean meal. In the experimental groups, varying percentages (3%, 6%, 9%, and 12%) of EGLP were substituted for the corn–soybean meal in the basal diet. In the diet, for days 1–21, the corn content was reduced from 1.90% to 8.20%, and the soybean meal content was lowered from 1.50% to 6.00%. Similarly, in the diet, for days 22–42, the corn content was decreased from 1.17% to 7.00%, while the soybean meal content was reduced by 1.50% to 6.00%. The experiment lasted 42 days and was divided into two phases: the brooding phase (days 1 to 21) and the finishing phase (days 22 to 42). The results show that substituting 3% and 6% EGLP for corn and soybean meal significantly increased the average daily gain (ADG) during the brooding period compared to the control group (p &lt; 0.01). Additionally, the group with a 3% substitution rate exhibited a significant increase in the average daily feed intake (ADFI) during the brooding phase (p &lt; 0.01). Throughout the 42-day experiment, substituting 3% and 6% of EGLP for maize and soybean meal did not significantly affect the overall growth performance of broilers (p &gt; 0.05). However, a 6% supplementation notably reduced the feed conversion ratio (FCR) (p &lt; 0.01). Both the 3% (EG3) EGLP and 6% (EG6) EGLP replacement meals significantly enhanced the antioxidant capacity of broiler chickens, as indicated by the increased levels of the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) (p &lt; 0.01). Additionally, broilers supplemented with 3–12% showed a marked increase in cecal short-chain fatty acids (SCFAs) compared to the control group (p &lt; 0.01). The 3% EGLP replacement diet also significantly boosted the prevalence of Lactobacillus in the cecum (p &lt; 0.01). Furthermore, after EGLP supplementation, there was a higher abundance of SCFA-metabolizing bacteria, particularly Alistipes and Christensenellaceae_R-7, compared to pre-treatment (p &lt; 0.05). The prevalence of Clostridium was significantly greater in the groups receiving 9% and 12% EGLP (p &lt; 0.05), while Butyrivibrio levels were notably higher after supplementation with 12% EGLP (p &lt; 0.05).

Microbial community acclimation during anaerobic digestion of high-oil food waste

Anaerobic digestion is one of the most promising options for the disposal of biodegradable food waste. However, the relatively high content of oil in food waste inhibits the conversion efficiency of anaerobic digestion because of the accumulation of long-chain fatty acids (LCFAs). In this study, activated anaerobic sludge was acclimated to accommodate high-oil conditions. The methane yield of high-oil food waste digested by the acclimated sludge increased by 24.9% compared to that digested by the raw sludge. To determine the internal changes in the acclimated sludge, the shifts in the microbial communities during the acclimation period were investigated via high-throughput sequencing (HTS) based on the 16 S rRNA gene. The results indicated that Bacteroidetes, Firmicutes, Chloroflexi and Proteobacteria were the dominant bacteria at the phylum level. The acclimation time allows some functional bacterial taxa to proliferate, such as Clostridium and Longilinea, which are able to degrade LCFAs and turn them into small organic molecules that also have nutrient value for other bacteria. Among the archaeal communities, the hydrogenotrophic methanogen Methanobacterium nearly supplanted the acetotrophic methanogen Methanosaeta. The time profiles of volatile fatty acids (VFAs) and pH during this period provided additional evidence for the success of the acclimation. This study demonstrated the effectiveness of acclimation and the dynamic of microbial communities, which further contributed to the management and resource utilization of high-oil food waste.

Growth performance and ruminal fermentation characteristics of Thai-native beef cattle fed cassava pulp fermented with Lactobacillus casei TH14 and additives.

Raw cassava pulp is a low-nutritional agro-industry residue with a high moist content that is susceptible to rot. Biodegradation of cassava pulp by adding Lactobacillus spp. plus stimulants could boost bio-acidity to preserve cassava pulp as ruminant feed. This investigation assessed the effect of ensiled cassava pulp without or with Lactobacillus casei TH14 (LTH14), urea, and molasses on the intake, digestibility, rumen fermentation, and growth performance of native Thai beef cattle. Eight Thai-native beef bulls (170.3 ± 20.2kg of initial body weight) were randomly assigned to two treatment groups in a completely randomized design: cassava pulp ensiled without additives (CPFNO; n = 4) and cassava pulp ensiled with the combination of LTH14 (2.5g per ton of fresh material), urea (4% DM), and molasses (4% DM) (CPFWA; n = 4). The intake of the concentrate diet and ensiled cassava pulp did not differ (p > 0.05) between the CPFNO and CPFWA groups, including final body weight, average daily gain (ADG), and feed conversion ratio (p > 0.05). However, CPFWA affected higher rice straw intake compared to the CPFNO group (p < 0.05). The intake and digestibility of crude protein (CP) were greater for the CPFWA group at 43.86% and 30.87%, respectively, compared to the CPFNO group (p < 0.05). Ruminal ammonia-nitrogen (NH3-N)and blood urea-nitrogen (BUN) were increased when animals were fed with CPFWA (p < 0.05). The average total volatile fatty acids (VFA) concentration of CPFWA was greater than that of CPFNO by 27.49% (p < 0.05). In conclusion, CPFWA supplementation can enhance rice straw intake, CP intake and digestion, total ruminal VFA concentration, and BUN levels, without adversely affecting growth performance.

Rifaximin alleviates intestinal barrier disruption and systemic inflammation via the PXR/NFκB/MLCK pathway and modulates intestinal Lachnospiraceae abundance in heat-stroke mice

Heatstroke is a critical condition with a high mortality rate and intestinal barrier dysfunction is a key factor in its progression to sepsis in some patients. This study aimed to explore the protective effects of rifaximin on the intestinal barrier in heat-stroke mice and the underlying mechanisms. A mouse model of heat stroke was established, followed by rifaximin intervention. Rifaximin significantly improved survival rates, reduced core body temperature, and alleviated intestinal tissue damage. Further mechanistic studies revealed that rifaximin restored heat stroke-induced damage to intestinal barrier function by upregulating the expression of the tight junction proteins, ZO-1 and occludin. Additionally, 16S rRNA sequencing showed that rifaximin significantly increased the abundance of Lachnospiraceae in the gut and enhanced short-chain fatty acid butyrate levels. In vitro experiment results revealed that butyrate promotes the expression of the intestinal epithelial cell protein MUC2, thereby strengthening the intestinal barrier. Rifaximin also activated the pregnane X receptor (PXR) signaling pathway and inhibited the NF-κB/MLCK signaling pathway, reducing the permeability of intestinal epithelial cells. This study demonstrated that rifaximin protects the intestinal barrier in mice with heat stroke through multiple pathways by modulating the gut microbiota, increasing butyrate production, and activating the PXR signaling pathway. These findings provide a new theoretical basis for the clinical application of rifaximin in heat stroke treatment.

The effect of prebiotic fibre on the gut microbiome and surgical outcomes in patients with prosthetic joint infection (PENGUIN) - study protocol for a randomised, double-blind, placebo-controlled trial (ACTRN12623001273673)

BackgroundProsthetic Joint Infection (PJI) is the most devastating complication of arthroplasty surgery and affects 1–5% of patients. Despite strict adherence to aseptic protocols and preventive measures, infection is the most common reason for revision arthroplasty, and the incidence is increasing. Treatment of PJI is challenging and often requires repeated major surgeries with sequentially poor results. The continued occurrence of PJI, and persistence after treatment, brings into question the current treatment paradigm. Preclinical evidence suggests a link between altered gut health and the risk of PJI in arthroplasty patients. Resistant starches helps to restore gut physiology by enhancing the beneficial microbiome and producing short-chain fatty acids, which have several health-conferring properties. The primary aim of this study is to investigate the effect of a commercially available prebiotic fibre formulation on the gut microbiome in PJI patients planned for a two-stage revision surgery.MethodsA double-blind placebo-controlled trial will assess the effect of 8-week supplementation of a commercially available prebiotic supplement in patients presenting with first-time PJI undergoing two-stage revision surgery. The supplementation phase will start after the first stage revision, and 80 patients will be randomised to receive either a test product (34 g of resistant starch) or a placebo (custard powder) daily for eight weeks. Stool and blood specimens will be collected at baseline, four weeks and eight weeks after the first-stage surgery and once at second-stage surgery. Gut microbiome profile, inflammatory cytokines and gut permeability biomarkers will be measured. Tissue specimens will be collected intra-operatively during first and second-stage surgeries. Baseline dietary patterns and gut symptoms will be recorded using validated questionnaires. Treatment outcomes will be reported for both cohorts using the Delphi criterion at one and two years after second-stage surgery.DiscussionThis will be the first study to investigate the relationship between gut health optimisation and preventing PJI recurrence in arthroplasty patients. If supplementation with resistant starch improves gut health and reduces systemic inflammation, optimising the gut microbiome will be a recommended preoperative management strategy for arthroplasty patients.Trial registration noACTRN12623001273673.

Unraveling the web of defense: the crucial role of polysaccharides in immunity.

The great potential of polysaccharides in immunological regulation has recently been highlighted in pharmacological and clinical studies. Polysaccharides can trigger immunostimulatory responses through molecular identification, intra- and intercellular communication via direct or indirect interactions with the immune system. Various immunostimulatory polysaccharides or their derivative compounds interacts at cellular level to boost the immune system, including arabinogalactans, fucoidans, mannans, xylans, galactans, hyaluronans, fructans, pectin and arabinogalactans, etc. These natural polysaccharides are derived from various plants, animals and microbes. A unique structural diversity has been identified in polysaccharides, while monosaccharides and glucosidic bonds mainly confer diverse biological activities. These natural polysaccharides improve antioxidant capacity, reduce the production of pro-inflammatory mediators, strengthen the intestinal barrier, influence the composition of intestinal microbial populations and promote the synthesis of short-chain fatty acids. These natural polysaccharides are also known to reduce excessive inflammatory responses. It is crucial to develop polysaccharide-based immunomodulators that could be used to prevent or treat certain diseases. This review highlights the structural features, immunomodulatory properties, underlying immunomodulatory mechanisms of naturally occurring polysaccharides, and activities related to immune effects by elucidating a complex relationship between polysaccharides and immunity. In addition, the future of these molecules as potential immunomodulatory components that could transform pharmaceutical applications at clinical level will also be highlighted.

Daikenchuto, a Japanese herbal medicine, ameliorates experimental colitis in a murine model by inducing secretory leukocyte protease inhibitor and modulating the gut microbiota.

Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD. Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs). Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner. These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.