Ginkgo biloba extract alleviates fatty liver hemorrhagic syndrome in laying hens via reshaping gut microbiota

Background Ginkgo biloba extract(GBE)is evidenced to be effective in the prevention and alleviation of metabolic disorders,including obesity,diabetes and fatty liver disease.However,the role of GBE in alleviating fatty liver hemorrhagic syndrome(FLHS)in laying hens and the underlying mechanisms remain to be elucidated.Here,we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.Results The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet(HFD)-induced FLHS laying hen model by decreasing the levels of TG,TC,ALT and ALP.The lipid accumulation and pathological score of liver were also relieved after GBE treatment.Moreover,GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH,SOD,T-AOC,GSH-PX and reducing MDA,and downregulated the expression of genes related to lipid synthesis(FAS,LXRα,GPAT1,PPARγand Ch REBP1)and inflammatory cytokines(TNF-α,IL-6,TLR4 and NF-κB)in the liver.Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota,particularly elevated the abundance of Megasphaera in the cecum.Meanwhile,targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs,acetate and propionate,which were positively correlated with the GBE-enriched gut microbiota.Finally,we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation(FMT).Conclusions We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota.Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Bringing gut microbiota into the spotlight of clinical research and medical practice

Despite the increasing scientific interest and expanding role of gut microbiota(GM)in human health,it is rarely reported in case reports and deployed in cli-nical practice.Proteins and metabolites produced by microbiota contribute to im-mune system development,energy homeostasis and digestion.Exo-and endoge-nous factors can alter its composition.Disturbance of microbiota,also known as dysbiosis,is associated with various pathological conditions.Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool.GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections.Ad-ditionally,it can influence response to treatments,including those for cancers,by altering drug bioavailability.A thorough understanding of its function has per-mitted significant development in therapeutics,such as probiotics and fecal trans-plantation.Hence,GM should be considered as a ground-breaking biological parameter,and it is advisable to be investigated and reported in literature in a more consistent and systematic way.

Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide

Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases mortality.Disruption of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis.We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro ke.An observational retrospective study was conducted.From May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy controls.Patients with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy controls.The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing.We also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy controls.The patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae family.Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation group.lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte riaceae.Next,the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model.In this model,transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.Ta ken togethe r,our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation.This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transfo rmation after stro ke.

Ginsenoside Rk3 modulates gut microbiota and regulates immune response of group 3 innate lymphoid cells to against colorectal tumorigenesis

The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.

Dynamic changes of rumen microbiota and serum metabolome revealed increases in meat quality and growth performances of sheep fed bio‑fermented rice straw

Background Providing high-quality roughage is crucial for improvement of ruminant production because it is an essential component of their feed.Our previous study showed that feeding bio-fermented rice straw(BF)improved the feed intake and weight gain of sheep.However,it remains unclear why feeding BF to sheep increased their feed intake and weight gain.Therefore,the purposes of this research were to investigate how the rumen micro-biota and serum metabolome are dynamically changing after feeding BF,as well as how their changes influence the feed intake,digestibility,nutrient transport,meat quality and growth performances of sheep.Twelve growing Hu sheep were allocated into 3 groups:alfalfa hay fed group(AH:positive control),rice straw fed group(RS:negative control)and BF fed group(BF:treatment).Samples of rumen content,blood,rumen epithelium,muscle,feed offered and refusals were collected for the subsequent analysis.Results Feeding BF changed the microbial community and rumen fermentation,particularly increasing(P<0.05)relative abundance of Prevotella and propionate production,and decreasing(P<0.05)enteric methane yield.The histomorphology(height,width,area and thickness)of rumen papillae and gene expression for carbohydrate trans-port(MCT1),tight junction(claudin-1,claudin-4),and cell proliferation(CDK4,Cyclin A2,Cyclin E1)were improved(P<0.05)in sheep fed BF.Additionally,serum metabolome was also dynamically changed,which led to up-regulating(P<0.05)the primary bile acid biosynthesis and biosynthesis of unsaturated fatty acid in sheep fed BF.As a result,the higher(P<0.05)feed intake,digestibility,growth rate,feed efficiency,meat quality and mono-unsaturated fatty acid concentration in muscle,and the lower(P<0.05)feed cost per kg of live weight were achieved by feeding BF.Conclusions Feeding BF improved the growth performances and meat quality of sheep and reduced their feed cost.Therefore,bio-fermentation of rice straw could be an innovative way for improving ruminant production with mini-mizing production costs.

Role of gut microbiota in Crohn’s disease pathogenesis:Insights from fecal microbiota transplantation in mouse model

BACKGROUND Inflammatory bowel disease,particularly Crohn’s disease(CD),has been associated with alterations in mesenteric adipose tissue(MAT)and the phenomenon termed“creeping fat”.Histopathological evaluations showed that MAT and intestinal tissues were significantly altered in patients with CD,with these tissues characterized by inflammation and fibrosis.AIM To evaluate the complex interplay among MAT,creeping fat,inflammation,and gut microbiota in CD.METHODS Intestinal tissue and MAT were collected from 12 patients with CD.Histological manifestations and protein expression levels were analyzed to determine lesion characteristics.Fecal samples were collected from five recently treated CD patients and five control subjects and transplanted into mice.The intestinal and mesenteric lesions in these mice,as well as their systemic inflammatory status,were assessed and compared in mice transplanted with fecal samples from CD patients and control subjects.RESULTS Pathological examination of MAT showed significant differences between CDaffected and unaffected colons,including significant differences in gut microbiota structure.Fetal microbiota transplantation(FMT)from clinically healthy donors into mice with 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced CD ameliorated CD symptoms,whereas FMT from CD patients into these mice exacerbated CD symptoms.Notably,FMT influenced intestinal permeability,barrier function,and levels of proinflammatory factors and adipokines.Furthermore,FMT from CD patients intensified fibrotic changes in the colon tissues of mice with TNBS-induced CD.CONCLUSION Gut microbiota play a critical role in the histopathology of CD.Targeting MAT and creeping fat may therefore have potential in the treatment of patients with CD.

Comprehensive analysis of the gut microbiome and posttranslational modifications elucidates the route involved in microbiota-host interactions

The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.

Fecal microbiota transplantation:whole grain highland barley improves glucose metabolism by changing gut microbiota

Highland barley(HB)is a high-altitude cereal with rich nutritional components and potential health benefits.To clarify its hypoglycemic effect and mechanism,we investigated the effect of whole grain HB and fecal microbiota transplantation(FMT)on glucose metabolism and gut microbiota in high-fat diet and streptozotocin(HFD/STZ)-induced diabetic mice.The results showed that HB(40%)significantly decreased fasting blood glucose and the area under the glucose tolerance curve,significantly increased insulin secretion and improved insulin resistance in HFD/STZ-induced diabetic mice(P<0.05).Inflammatory factors and blood lipid indices were also significantly alleviated after 12 weeks of 40%HB intervention(P<0.05).Additionally,beneficial bacteria,such as Bifidobacterium and Akkermansia,were significantly enriched in the gut of diabetic mice after whole grain HB intervention.Meanwhile,the results of further FMT experiments verified that the fecal microbiota after the 40%HB intervention not only significantly increased the relative abundance of Bifidobacterium and Akkermansia but also effectively improved glucose metabolism and alleviated the inflammatory state in HFD/STZ-induced diabetic mice.Collectively,our study confirmed the bridge role of gut microbiota in improving glucose metabolism of whole grain HB,which could promote the development of precision nutrition.

Insights into microbiota community dynamics and flavor development mechanism during golden pomfret(Trachinotus ovatus)fermentation based on single-molecule real-time sequencing and molecular networking analysis

Popular fermented golden pomfret(Trachinotus ovatus)is prepared via spontaneous fermentation;however,the mechanisms underlying the regulation of its flavor development remain unclear.This study shows the roles of the complex microbiota and the dynamic changes in microbial community and flavor compounds during fish fermentation.Single-molecule real-time sequencing and molecular networking analysis revealed the correlations among different microbial genera and the relationships between microbial taxa and volatile compounds.Mechanisms underlying flavor development were also elucidated via KEGG based functional annotations.Clostridium,Shewanella,and Staphylococcus were the dominant microbial genera.Forty-nine volatile compounds were detected in the fermented fish samples,with thirteen identified as characteristic volatile compounds(ROAV>1).Volatile profiles resulted from the interactions among the microorganisms and derived enzymes,with the main metabolic pathways being amino acid biosynthesis/metabolism,carbon metabolism,and glycolysis/gluconeogenesis.This study demonstrated the approaches for distinguishing key microbiota associated with volatile compounds and monitoring the industrial production of high-quality fermented fish products.

D-Psicose intake exacerbates dextran sulfate sodium-induced colitis in mice through alteration in the gut microbiota and dysfunction of mucosal barrier

D-Psicose,as a low-calorie rare sugar,has attracted a lot of attention in recent years for alternating to sucrose.The anti-obesity effect of D-psicose has been extensively confirmed in previous studies,however,the impact of D-psicose on colitis remains vague.Here,we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice.The pathological symptoms,inflammatory cytokines levels,gut microbiota composition,short chain fatty acids(SCFAs)production and colonic barrier integrity were comprehensively evaluated.The results confirmed that D-psicose intervention aggravated colitis,characterized by the exacerbation of colon shortening,increase of colonic inflammatory infiltration,and marked exaltation of disease activity indices and IL-6,IL-1βand TNF-αlevels.Further,the dysfunction of gut microbiota was identified in the psicose group.The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group.Moreover,the production of SCFAs was suppressed in the psicose group,accompanied by a decrease in the level of mucin 2(Muc-2).Collectively,the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs,which leads to the damage of the mucosal barrier and the intensifi cation of inflammatory invasion.

Effects of Rosa roxburghii&edible fungus fermentation broth on immune response and gut microbiota in immunosuppressed mice

With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Dual-directional regulation of spinal cord injury and the gut microbiota

There is increasing evidence that the gut microbiota affects the incidence and progression of central nervous system diseases via the brain-gut axis.The spinal cord is a vital important part of the central nervous system;however,the underlying association between spinal cord injury and gut interactions remains unknown.Recent studies suggest that patients with spinal cord injury frequently experience intestinal dysfunction and gut dysbiosis.Alterations in the gut microbiota can cause disruption in the intestinal barrier and trigger neurogenic inflammatory responses which may impede recovery after spinal cord injury.This review summarizes existing clinical and basic research on the relationship between the gut microbiota and spinal cord injury.Our research identified three key points.First,the gut microbiota in patients with spinal cord injury presents a key characteristic and gut dysbiosis may profoundly influence multiple organs and systems in patients with spinal cord injury.Second,following spinal cord injury,weakened intestinal peristalsis,prolonged intestinal transport time,and immune dysfunction of the intestine caused by abnormal autonomic nerve function,as well as frequent antibiotic treatment,may induce gut dysbiosis.Third,the gut microbiota and associated metabolites may act on central neurons and affect recovery after spinal cord injury;cytokines and the Toll-like receptor ligand pathways have been identified as crucial mechanisms in the communication between the gut microbiota and central nervous system.Fecal microbiota transplantation,probiotics,dietary interventions,and other therapies have been shown to serve a neuroprotective role in spinal cord injury by modulating the gut microbiota.Therapies targeting the gut microbiota or associated metabolites are a promising approach to promote functional recovery and improve the complications of spinal cord injury.

Dietary sodium acetate and sodium butyrate improve high-carbohydrate diet utilization by regulating gut microbiota, liver lipid metabolism, oxidative stress, and inflammation in largemouth bass(Micropterus salmoides)

Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level.Method Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate(SA) and sodium butyrate(SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC(9% starch), HC(18% starch), HCSA(18% starch;2 g/kg SA), HCSB(18% starch;2 g/kg SB), and HCSASB(18% starch;1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d.Results We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy(ATG101, LC3B and TFEB), promoting lipolysis(CPT1α, HSL and AMPKα), and inhibiting adipogenesis(FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver(CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors(IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate(Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition.Conclusions In conclusion, dietary SA and SB can reduce hepatic lipid deposition;and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.

Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are limited.Herein,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral ovariectomy.After 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical testing.The results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid biosynthesis.Furthermore,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and microarchitecture.Mechanistically,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase 5b.Overall,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

More on the interplay between gut microbiota,autophagy,and inflammatory bowel disease is needed

The concept of inflammatory bowel disease(IBD),which encompasses Crohn’s disease and ulcerative colitis,represents a complex and growing global health concern resulting from a multifactorial etiology.Both dysfunctional autophagy and dysbiosis contribute to IBD,with their combined effects exacerbating the related inflammatory condition.As a result,the existing interconnection between gut microbiota,autophagy,and the host’s immune system is a decisive factor in the occurrence of IBD.The factors that influence the gut microbiota and their impact are another important point in this regard.Based on this initial perspective,this manuscript briefly highlighted the intricate interplay between the gut microbiota,autophagy,and IBD pathogenesis.In addition,it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context.Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms,which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.