IAH/ACS诊疗中应用床旁超声GUTS Protocol导向的准确性研究

目的:探讨腹腔高压(IAH)/腹腔间隔室综合征(ACS)诊疗中应用床旁超声GUTS Protocol导向的准确性。方法:前瞻性纳入2020年1月—12月广东省人民医院珠海医院ICU预期入住超过24 h的IAH/ACS患者33例作为研究对象,根据治疗方式进行分组。传统治疗组根据腹内压诊断的标准以及临床特征诊断的标准进行诊断,并由重症临床经验的高年资医生根据临床经验对患者进行处理,拟定并记录初步诊断与初步诊疗计划。GUTS Protocol组拟行GUTS Protocol采集超声图像,记录采图时的临床指标,根据测量结果,结合临床信息,在GUTS Protocol表中勾选病理生理层面、临床层面的诊断及初步治疗方案。根据患者的治疗效果得出IAH/ACS病理生理学、临床层面的最终诊断和最恰当治疗方案,作为金标准,比较GUTS Protocol组与传统治疗组的诊疗计划的准确性。结果GUTS Protocol组诊疗计划的准确性高于传统治疗组,差异有统计学意义(P<0.05)。结论GUTS流程能实时准确的评价胃肠道情况及IAH带来的器官功能变化,更能有针对性的治疗IAH。

stomach、abdomen、belly、guts辨析

1.stomach在这一组词中用得最普遍,它可指腹腔内部的消化器官,尤指胃,也可指外腹部。如: It takes time for the food in the stomach to be digested. 消化胃里的食物是需要时间的。

Gut microbial regulation of innate and adaptive immunity after traumatic brain injury

Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.

Correlation between the gut microbiome and neurodegenerative diseases:a review of metagenomics evidence

A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.

Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

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.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Natural sources,refined extraction,biosynthesis,metabolism,and bioactivities of dietary polymethoxyflavones(PMFs)

Polymethoxyflavones(PMFs)are a type of uncommon dietary flavonoids,characterized by more than one methoxy group,which exist in limited plant species,like Citrus species and Kaempferia parviflora.In addition,different PMFs,such as nobiletin,sinensetin,tangeretin,and casticin,have been isolated from these natural sources.PMFs have received increasing attention due to their multiple bioactivities,such as antioxidant,anti-inflammatory,anti-cancer,metabolic regulatory,immunoregulatory,neuroprotective,and skin protective effects.These bioactivities of PMFs should be associated with the regulation of critical molecular targets and the interaction with gut microbiota.In order to provide a comprehensive and updated review of PMFs,their natural sources,refined extraction,biosynthesis,metabolism,and bioactivities are summarised and discussed,with the emphasis on the molecular mechanisms of PMFs on regulating different chronic diseases.Overall,PMFs may be promising flavonoids to the forefront of nutraceuticals for the prevention and/or treatment of certain human chronic diseases.

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.

Interplay between microglia and environmental risk factors in Alzheimer's disease

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

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.

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.

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.

Pre‑hatch thermal manipulation of embryos and post‑hatch baicalein supplementation mitigated heat stress in broiler chickens

Background High environmental temperatures induce heat stress in broiler chickens,affecting their health and pro-duction performance.Several dietary,managerial,and genetics strategies have been tested with some success in mitigating heat stress(HS)in broilers.Developing novel HS mitigation strategies for sustaining broiler production is critically needed.This study investigated the effects of pre-hatch thermal manipulation(TM)and post-hatch baica-lein supplementation on growth performance and health parameters in heat-stressed broilers.Results Six hundred fertile Cobb 500 eggs were incubated for 21 d.After candling on embryonic day(ED)10,238 eggs were thermally manipulated at 38.5℃ with 55%relative humidity(RH)from ED 12 to 18,then transferred to the hatcher(ED 19 to 21,standard temperature)and 236 eggs were incubated at a controlled temperature(37.5℃)till hatch.After hatch,180-day-old chicks from both groups were raised in 36 pens(n=10 birds/pen,6 replicates per treatment).The treatments were:1)Control,2)TM,3)control heat stress(CHS),4)thermal manipulation heat stress(TMHS),5)control heat stress supplement(CHSS),and 6)thermal manipulation heat stress supplement(TMHSS).All birds were raised under the standard environment for 21 d,followed by chronic heat stress from d 22 to 35(32–33℃ for 8 h)in the CHS,TMHS,CHSS,and TMHSS groups.A thermoneutral(22–24℃)environment was maintained in the Control and TM groups.RH was constant(50%±5%)throughout the trial.All the data were analyzed using one-way ANOVA in R and GraphPad software at P<0.05 and are presented as mean±SEM.Heat stress significantly decreased(P<0.05)the final body weight and ADG in CHS and TMHS groups compared to the other groups.Embryonic TM significantly increased(P<0.05)the expression of heat shock protein-related genes(HSP70,HSP90,and HSPH1)and antioxidant-related genes(GPX1 and TXN).TMHS birds showed a significant increment(P<0.05)in total cecal volatile fatty acid(VFA)concentration compared to the CHS birds.The cecal microbial analysis showed significant enrichment(P<0.05)in alpha and beta diversity and Coprococcus in the TMHSS group.Conclusions Pre-hatch TM and post-hatch baicalein supplementation in heat-stressed birds mitigate the detrimental effects of heat stress on chickens’growth performance,upregulate favorable gene expression,increase VFA produc-tion,and promote gut health by increasing beneficial microbial communities.

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.

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.

Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

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.

Microbial phenolic metabolites 3-(3',4'-dihydroxyphenyl)propanoic acid and 3',4'-dihydroxyphenylacetic acid prevent obesity in mice fed high-fat diet

Obesity is associated with numerous metabolic disorders,and dietary polyphenols have been confirmed to have beneficial effects on the metabolism in obesity.However,the effect of 3-(3’,4’-dihydroxyphenyl)propanoic acid(DHPA)and 3’,4’-dihydroxyphenylacetic acid(DHAA),two main metabolites of dietary polyphenols,on obesity remains poorly understood.In this study,DHPA and DHAA were found to alleviate obesity,as well as regulate insulin resistance,lipid metabolism,and oxidative stress response in high-fat diet(HFD)mice.Surprisingly,the 16S rRNA sequencing and UHPLC-Q-TOF/MS demonstrated that DHPA and DHAA only slightly disturbed the intestinal microbiome,but significantly altered the urine metabolome of HFD mice mainly by regulating pentose and glucuronate interconversion,tyrosine metabolism,pentose phosphate and tricarboxylic acid(TCA)cycle as indicated by metabolic pathway analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Correlation analysis revealed that the differential metabolites are strongly associated with body weight,blood glucose,insulin level,and superoxide dismutase(SOD)enzyme activity.Our results revealed that DHPA and DHAA exert their anti-obesity effect by regulating important metabolites in the glucose,lipid and tyrosine metabolism pathways.

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.