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Leaky gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide‑Mediated Toll‑Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway

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Neuroscience Bulletin 2023年第6期39卷 911-928页

作者： Fang Li Haoran Ke Siqi Wang Wei Mao Cexiong Fu Xi Chen Qingqing Fu Xiaori Qin Yonghua Huang Bidan Li Shibing Li Jingying Xing Minhui Wang Wenlin Deng Department of Gastroenterology Gastroenterology Endoscopy CenterHainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Gastroenterology First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhou 510120China Department of Hepatopancreatobiliary Surgery Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Otolaryngology‑Head and Neck Surgery Hospital of Hainan ProvinceDepartment of OtorhinolaryngologyHead and Neck SurgeryHainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Radiology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Pediatric Surgery Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Gastroenterology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Nephrology Department of NephrologyHainan Affiliated Hospital of Hainan Medical CollegeHainan General HospitalHaikou 570311China Department of Pediatrics The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China

Increased intestinal barrier permeability,leaky gut,has been reported in patients with autism.However,its contribution to the development of autism has not been determined.We selected dextran sulfate sodium(DSS)to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis.DSS treatment resulted in a decreased affinity for social proximity;however,autistic behaviors in mice were improved after the administration of metformin.We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors.The concentration of lipopolysaccharides in blood decreased after the administration of metformin.The expression levels of the key molecules in the toll-like receptor 4(TLR4)–myeloid differentiation factor 88(MyD88)–nuclear factor kappa B(NF-κB)pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed.Thus,“leaky gut”could be a trigger for the development of autism via activation of the lipopolysaccharide-mediated TLR4–MyD88–NF-κB pathway.

关键词： Autism gut Lipopolysaccharide Toll-like receptor 4 Metformin

Identification of lipid droplets in gut bacteria

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Protein & Cell 2023年第2期14卷 143-148页

作者： Kai Zhang Chang Zhou Zemin Li Xuehan Li Ziyun Zhou Linjia Cheng Ahmed Hammad Mirza Yumeng Shi Bingbing Chen Mengwei Zhang Liujuan Cui Congyan Zhang Taotao Wei Xuelin Zhang Shuyan Zhang Pingsheng Liu National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China School of Kinesiology and Health Capital University of Physical Education and SportsBeijing 100191China University of Chinese Academy of Sciences Beijing 100049China Hebei Normal University Shijiazhuang 050024China Hainan University Haikou 570228China

Dear Editor,The field of gut microbiota is progressing rapidly and thus,appellations like the last human organ,a separate organ,a forgotten organ,and a new organ have been applied to gut microbiota to emphasize its vital functions in our body(Chang and Kao,2019).gut microbiota has been shown to play a central role in the regulation of human lipid metabolism and be associated with lipid metabolism disorders when aberrant,through composition and microbial metabolites.

关键词： metabolism gut vital

Commentary:gut microbiota reduce the risk of hyperuricemia and gout in the human body

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Acta Pharmaceutica Sinica B 2024年第1期14卷 433-435页

作者： Lin Wang Jianping Ye Metabolic Disease Research Center Zhengzhou University Affiliated Zhengzhou Central HospitalZhengzhou 450007China Research Center for Basic Medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Gout,a prevalent and painful metabolic disease often associated with obesity and aging,is caused by the deposition of urate crystals in joints,bones,or soft tissues1.Urate is an intermediate metabolite within the purine degradation pathway,predominantly derived from uric acid under physiological pH levels.Hyperuricemia occurs due to excessive uric acid production or insufficient excretion2,which is associated with various chronic diseases,including type 2 diabetes.

关键词： Uric acid Gout Microbiota gut Uricase

The role of cellular and molecular neuroimmune crosstalk in gut immunity

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Cellular & Molecular Immunology 2023年第11期20卷 1259-1269页

作者： Daping Yang Nicole Almanzar Isaac M.Chiu Department of Immunology Harvard Medical SchoolBostonMA02115USA

The gastrointestinal tract is densely innervated by the peripheral nervous system and populated by the immune system.These two systems critically coordinate the sensations of and adaptations to dietary,microbial,and damaging stimuli from the external and internal microenvironment during tissue homeostasis and inflammation.The brain receives and integrates ascending sensory signals from the gut and transduces descending signals back to the gut via autonomic neurons.Neurons regulate intestinal immune responses through the action of local axon reflexes or through neuronal circuits via the gut-brain axis.This neuroimmune crosstalk is critical for gut homeostatic maintenance and disease resolution.In this review,we discuss the roles of distinct types of gut-innervating neurons in the modulation of intestinal mucosal immunity.We will focus on the molecular mechanisms governing how different immune cells respond to neural signals in host defense and inflammation.We also discuss the therapeutic potential of strategies targeting neuroimmune crosstalk for intestinal diseases.

关键词： Neuroimmunology Neuroimmune Host defense gut Sensory

Restored intestinal integrity,nutrients transporters,energy metabolism,antioxidative capacity and decreased harmful microbiota were associated with IUGR piglet's catch-up growth before weanling

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Journal of Animal Science and Biotechnology 2023年第1期14卷 390-408页

作者： Chang Cui Caichi Wu Jun Wang Ziwei Ma Xiaoyu Zheng Pengwei Zhu Nuan Wang Yuhua Zhu Wutai Guan Fang Chen Guangdong Provincial Key Laboratory of Animal Nutrition Control College of Animal ScienceSouth China Agricultural UniversityGuangzhou 510642China. Shenzhen Kingsino Technology CO. LTDShenzhen 518107China. Shenzhen Institute of Nutrition and Health Huazhong Agricultural UniversityWuhan 430070China. Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural SciencesShenzhen 518116China. College of Animal Science and National Engineering Research Center for Breeding Swine Industry South China Agricultural UniversityGuangzhou 510642China. Guangdong Laboratory for Lingnan Modern Agriculture South China Agricultural UniversityGuangzhou 510642China.

Background:Intrauterine growth restriction(IUGR)is a major inducer of higher morbidity and mortality in the pig industry and catch-up growth(CUG)before weanling could significantly restore this negative influence.But there was limited knowledge about the underlying mechanism of CUG occurrence.Methods:Eighty litters of newborn piglets were divided into normal birth weight(NBW)and IUGR groups according to birth weight.At 26 d,those piglets with IUGR but over average body weight of eighty litters of weaned piglets were considered as CUG,and the piglets with IUGR still below average body weight were considered as NCUG.This study was conducted to systemically compare the intestinal difference among NBW,CUG and NCUG weaned piglets considering the crucial role of the intestine for piglet growth.Results:The results indicated that the m RNA expression of nutrients(amino acids,glucose,and fatty acids)transporters,and mitochondrial electron transport chain(ETC)I were upregulated in CUG piglets'gut with improved morphology compared with those NCUG,as well as the ratio of P-AMPK/AMPK protein expression which is the indicator of energy metabolism.Meanwhile,CUG piglet's gut showed higher antioxidative capacity with increased SOD and GSHPx activity,decreased MDA levels,as well as higher m RNA expressions of Nrf2,Keap1,SOD,and GSH-Px.Furthermore,inflammatory parameters including TNF-α,IL-1β,IL-6,and IL-12 factors,and the activation of MAPK and NF-κB signaling pathways were significantly elevated in the NCUG intestine,while the protein expression of ZO-1,Occludin and Claudin-1 was reduced.The alpha diversity of fecal microbiota was higher in CUG piglets in contrast with NCUG piglets,and the increased beneficial bacteria and decreased pathogenic bacteria was also observed in CUG piglets.Conclusions:CUG piglet's intestine showed comprehensive restoration including higher nutrients transport,energy metabolism,antioxidant capacity,and intestinal physical barrier,while lower oxidative stress,inflammatory response,and pathogenic microbi

关键词： Antioxidative capacity Catch-up growth gut Intrauterine growth retardation Piglets

Crosstalk between trace elements and T-cell immunity during early-life health in pigs

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中国科学:生命科学英文版 2023年第9期66卷 1994-2005页

作者： Shunshun Jin Liuqin He Chengbo Yang Xinmiao He Heshu Chen Yanzhong Feng Wenjie Tang Jianzhong Li Di Liu Tiejun Li Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation Hunan International Joint Laboratory of Animal Intestinal Ecology and HealthCollege of Life SciencesHunan Normal UniversityChangsha 410081China Department of Animal Science University of ManitobaWinnipegManitoba R3T2N2Canada CAS Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureHunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionChangsha 410125China Heilongjiang Academy of Agricultural Sciences Harbin 150086China Animal Breeding and Genetics Key Laboratory of Sichuan Province Sichuan Animal Science AcademyChengdu 610066China

With gradual ban on the use of antibiotics, the deficiency and excessive use of trace elements in intestinal health is gaining attention. In mammals, trace elements are essential for the development of the immune system, specifically T-cell proliferation,and differentiation. However, there remain significant gaps in our understanding of the effects of certain trace elements on T-cell immune phenotypes and functions in pigs. In this review, we summarize the specificity, development, subpopulations, and responses to pathogens of porcine T cells and the effects of functional trace elements(e.g., iron, copper, zinc, and selenium) on intestinal T-cell immunity during early-life health in pigs. Furthermore, we discuss the current trends of research on the crosstalk mechanisms between trace elements and T-cell immunity. The present review expands our knowledge of the association between trace elements and T-cell immunity and provides an opportunity to utilize the metabolism of trace elements as a target to treat various diseases.

关键词： trace elements T cells pig gut immunity

gut microbiota and metabolic syndrome

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Chinese Medical Journal 2020年第7期133卷 808-816页

作者： Peng-Xu Wang Xin-Ru Deng Chen-Hong Zhang Hui-Juan Yuan department of Endocrinology Henan University People's HospitalHenan Provincial People's HospitalZhengzhouHenan 450003China State Key Laboratory of Microbial Metabolism School of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China.

Metabolic syndrome(MetS)describes a set of risk factors that can eventually lead to the occurrence of cardiovascular and cerebrovascular disease.A detailed understanding of the MetS mechanism will be helpful in developing effective prevention strategies and appropriate intervention tools.In this article,we discuss the relationship between the clinical symptoms of MetS and differences in the gut microbial community compared with healthy individuals,characterized by the proliferation of potentially harmful bacteria and the inhibition of beneficial ones.Interactions between gut microbiota and host metabolism have been shown to be mediated by a number of factors,including inflammation caused by gut barrier defects,short-chain fatty acids metabolism,and bile acid metabolism.However,although we can clearly establish a causal relationship between gut microbial profiles and MetS in animal experiments,the relationship between them is still controversial in humans.Therefore,we need more clinical studies to augment our understanding of how we can manipulate the gut microbiota and address the role of the gut microbiota in the prevention and treatment of MetS.

关键词： Metabolic syndrome gut microbiota Inflammation Short-chain fatty acids Bile acids

gut Microbiome Alterations in COVID-19

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Genomics, Proteomics & Bioinformatics 2021年第5期19卷 679-688页

作者： Tao Zuo Xiaojian Wu Weiping Wen Ping Lan Guangdong Institute of Gastroenterology The Sixth Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhou 510655China Center for Fecal Microbiota Transplantation Research The Sixth Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhou 510655China Department of Colorectal Surgery The Sixth Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhou 510655China Department of Otorhinolaryngology Head and Neck SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhou 510080China Guangzhou Key Laboratory of Otorhinolaryngology Guangzhou 510080China Department of Otorhinolaryngology Head and Neck SurgeryThe Sixth Affiliated Hospital of Sun Yat-sen UniversitySun Yat-sen UniversityGuangzhou 510655China

Since the outset of the coronavirus disease 2019(COVID-19)pandemic,the gut microbiome in COVID-19 has garnered substantial interest,given its significant roles in human health and pathophysiology.Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19,including the bacterial microbiome,mycobiome,and virome.Overall,the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19,together with a decrease in gut microbiome diversity.Beyond the existence of severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2),the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria,fungi,and eukaryotic viruses,which are also associated with disease severity and presentation.Meanwhile,a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19.Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution,coinciding with‘long COVID’(also known as postacute sequelae of COVID-19).The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu.The impaired host immunity and distorted gut microbial ecology,particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida,may hinder the reassembly of the gut microbiome post COVID-19.Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection,as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.

关键词： COVID-19 gut Microbiome Immunity Infection

Uncovering novel human gut virome using ultra-deep metagenomic sequencing

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Chinese Medical Journal 2022年第20期135卷 2395-2397页

作者： Harry Cheuk Hay Lau Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health Sciencesthe Chinese University of Hong KongHong Kong SARChina

Human gastrointestinal tract harbors trillions of commensal microbes including bacteria,viruses,and fungi to form an ecological community,commonly known as the gut microbiome.Being the second most dominant taxonomic kingdom in the gut(5.8%of total microbiome DNA),enteric viruses are increasingly acknowledged for their roles in shaping the overall composition of the gut microbiome and maintaining human health.[1,2]Recent advancements in metagenomic sequencing have brought breakthrough in deciphering the features and functions of the gut virome.

关键词： breakthrough harbor gut