Umbilical cord mesenchymal stem cell exosomes alleviate necrotizing enterocolitis in neonatal mice by regulating intestinal epithelial cells autophagy

BACKGROUND Necrotizing enterocolitis(NEC)is a severe gastrointestinal disease that affects premature infants.Although mounting evidence supports the therapeutic effect of exosomes on NEC,the underlying mechanisms remain unclear.AIM To investigate the mechanisms underlying the regulation of inflammatory response and intestinal barrier function by umbilical cord mesenchymal stem cell(UCMSCs)exosomes,as well as their potential in alleviating NEC in neonatal mice.METHODS NEC was induced in 5-d-old C57BL/6 pups through hypoxia and gavage feeding of formula containing lipopolysaccharide(LPS),after which the mice received human UCMSC exosomes(hUCMSC-exos).The control mice were allowed to breastfeed with their dams.Ileal tissues were collected from the mice and analyzed by histopathology and immunoblotting.Colon tissues were collected from NEC neonates and analyzed by immunofluorescence.Molecular biology and cell culture approaches were employed to study the related mechanisms in intestinal epithelial cells.RESULTS We found that autophagy is overactivated in intestinal epithelial cells during NEC,resulting in reduced expression of tight junction proteins and an increased inflammatory response.The ability of hUCMSC-exos to ameliorate NEC in a mouse model was dependent on decreased intestinal autophagy.We also showed that hUCMSC-exos alleviate the inflammatory response and increase migration ability in intestinal epithelial cells induced by LPS.CONCLUSION These results contribute to a better understanding of the protective mechanisms of hUCMSC-exos against NEC and provide a new theoretical and experimental foundation for NEC treatment.These findings also enhance our understanding of the role of the autophagy mechanism in NEC,offering potential avenues for identifying new therapeutic targets.

Gut microbiota modulating intestinal stem cell differentiation

Proliferation and differentiation of intestinal stem cell(ISC)to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation.However,when this disordered proliferation continues,it induces the ISC to enter a cancerous state.The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis.Micro-biota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors,while in steady state,differentiated colono-cytes are able to break down such metabolites,thereby protecting stem cells at the gut crypt.In the future,the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism

AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury. METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption. CONCLUSION: Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.

Current understanding concerning intestinal stem cells

In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad. However, mutations in some of the key regulator genes associated with these signaling pathways, such as APC, Kras and Smad4, are also highly associated with gut malformations. At this point, clarifying the biological characteristics of intestinal stem cells will increase the feasibility of preventing or treating some intestinal diseases, such as colorectal cancer. Moreover, as preclinical data demonstrate the therapeutic effects of colon stem cells on murine models of experimental colitis, the prospects of stem cell-based regenerative treatments for ulcerous lesions in the gastrointestinal tract will be improved all the same.

Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation

AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.

Modulation of stem cell fate in intestinal homeostasis,injury and repair

The mammalian intestinal epithelium constitutes the largest barrier against the external environment and makes flexible responses to various types of stimuli.Epithelial cells are fast-renewed to counteract constant damage and disrupted barrier function to maintain their integrity.The homeostatic repair and regeneration of the intestinal epithelium are governed by the Lgr5+intestinal stem cells(ISCs)located at the base of crypts,which fuel rapid renewal and give rise to the different epithelial cell types.Protracted biological and physicochemical stress may challenge epithelial integrity and the function of ISCs.The field of ISCs is thus of interest for complete mucosal healing,given its relevance to diseases of intestinal injury and inflammation such as inflammatory bowel diseases.Here,we review the current understanding of the signals and mechanisms that control homeostasis and regeneration of the intestinal epithelium.We focus on recent insights into the intrinsic and extrinsic elements involved in the process of intestinal homeostasis,injury,and repair,which fine-tune the balance between self-renewal and cell fate specification in ISCs.Deciphering the regulatory machinery that modulates stem cell fate would aid in the development of novel therapeutics that facilitate mucosal healing and restore epithelial barrier function.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells Intestinal stem cells and celiac disease

Stem cells(SCs)are the key to tissue genesis and regeneration.Given their central role in homeostasis,dysfunctions of the SC compartment play a pivotal role in the development of cancers,degenerative disorders,chronic inflammatory pathologies and organ failure.The gastrointestinal tract is constantly exposed to harsh mechanical and chemical conditions and most of the epithelial cells are replaced every 3 to 5 d.According to the so-called Unitarian hypothesis,this renewal is driven by a common intestinal stem cell(ISC)residing within the crypt base at the origin of the crypt-to-villus hierarchical migratory pattern.Celiac disease(CD)can be defined as a chronic immune-mediated disease that is triggered and maintained by dietary proteins(gluten)in genetically predisposed individuals.Many advances have been achieved over the last years in understanding of the pathogenic interactions among genetic,immunological and environmental factors in CD,with a particular emphasis on intestinal barrier and gut microbiota.Conversely,little is known about ISC modulation and deregulation in active celiac disease and upon a gluten-free diet.Nonetheless,bone marrow-derived SC transplantation has become an option for celiac patients with complicated or refractory disease.This manuscript summarizes the"state of the art"regarding CD and ISCs,their niche and potential role in the development and treatment of the disease.

Monomorphic epitheliotropic intestinal T-cell lymphoma with bone marrow involved: A case report

BACKGROUND Monomorphic epithelial intestinal T-cell lymphoma(MEITL)is a rare type of peripheral T-cell lymphoma.The clinical manifestations are diarrhea,abdominal pain,perforation and an abdominal mass.CASE SUMMARY We present a 52-year-old female patient who was diagnosed with MEITL.Further disease progression was observed after multiline chemotherapy.Eventually,the patient died of a severe infection.CONCLUSION MEITL is a rare intestinal primary T-cell lymphoma with aggressive behavior,a high risk of severe life-threatening complications,and a poor prognosis.

Update on small intestinal stem cells

Among somatic stem cells, those residing in the intestine represent a fascinating and poorly explored research field. Particularly, somatic stem cells reside in the small intestine at the level of the crypt base, in a constant balance between self-renewal and differentiation. Aim of the present review is to delve into the mechanisms that regulate the delicate equilibrium through which intestinal stem cells orchestrate intestinal architecture. To this aim, special focus will be addressed to identify the integrating signals from the surrounding niche, supporting a model whereby distinct cell populations facilitate homeostatic vs injury-induced regeneration.

Crypt region localization of intestinal stem cells in adults

The intestinal epithelial lining plays a central role in the digestion and absorption of nutrients,but exists in a harsh luminal environment that necessitates continual renewal.This renewal process involves epithelial cell proliferation in the crypt base and later cell migration from the crypt base to the luminal surface.This process is dependent on multi-potent progenitor cells,or stem cells,located in each crypt.There are about 4 to 6 stem cells per crypt,and these stem cells are believed to generate distinct end-differentiated epithelial cell types,including absorptive cells,goblet cells,enteroendocrine cells and Paneth cells,while also maintaining their own progenitor cell state.Earlier studies suggested that intestinal stem cells were located either in the crypt base interspersed between the Paneth cells [i.e.crypt base columnar(CBC) cell model] or at an average position of 4 cells from the crypt base [i.e.label-retaining cells(LRC +4) model].Recent studies have employed biomarkers in the in vivo mammalian state to more precisely evaluate the location of these progenitor cells in the intestinal crypt.Most notable of these novel markers are Lgr5,a gene that encodes a G-protein-coupled receptor with expression restricted to CBC cells,and Bmi 1,which encodes a chromatin remodeling protein expressed by LRC.These studies raise the possibility that there may be separate stem cell lines or different states of stem cell activation involved in the renewal of normal mammalian intestinal tract.

Adipose-derived mesenchymal stem cells alleviate TNBS-induced colitis in rats by influencing intestinal epithelial cell regeneration, Wnt signaling, and T cell immunity

BACKGROUND Conventional Crohn’s disease(CD)treatments are supportive rather than curative and have serious side effects.Adipose-derived mesenchymal stem cells(ADSCs)have been gradually applied to treat various diseases.The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear.AIM To investigate the effect of ADSC administration on CD and explore the potential mechanisms.METHODS Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid(TNBS)to establish a rat model of CD,followed by tail injections of green fluorescent protein(GFP)-modified ADSCs.Flow cytometry,qRT-PCR,and Western blot were used to detect changes in the Wnt signaling pathway,T cell subtypes,and their related cytokines.RESULTS The isolated cells showed the characteristics of ADSCs,including spindle-shaped morphology,high expression of CD29,CD44,and CD90,low expression of CD34 and CD45,and osteogenic/adipogenic ability.ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD.Furthermore,serum anti-sacchromyces cerevisiae antibody and panti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSCtreated rats.Mechanistically,the GFP-ADSCs were colocalized with intestinal epithelial cells(IECs)in the CD rat model.GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression,decreased noncanonical Wnt signaling pathway expression,and increased apoptosis rates and protein level of cleaved caspase-3 in rats.In addition,ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production,disturbed T cell subtypes,and their related markers in rats.CONCLUSION Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation,the Wnt signaling pathway,and T cell immunity.

Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.

Induced pluripotent stem cells for therapy personalization in pediatric patients:Focus on drug-induced adverse events

Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric patients.Indeed,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalization,disability or even death.In addition,pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs,leading,in some cases,to more severe consequences.To improve the comprehension,and thus the prevention,of ADRs,the set-up of sensitive and personalized assays is urgently needed.Important progress is represented by the possibility of setting up groundbreaking patient-specific assays.This goal has been powerfully achieved using induced pluripotent stem cells(iPSCs).Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body,this model may be accurate in predicting drug toxicity,especially when this toxicity is related to individual genetic differences.This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs,with particular attention to drugs used in the pediatric field.We especially focused on the intestinal,hepatic,pancreatic,renal,cardiac,and neuronal levels,also discussing progress in organoids creation.The latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine,liver,pancreas,kidney,heart,and brain.Based on the existing knowledge,these models are powerful and promising tools in multiple clinical applications including toxicity screening,disease modeling,personalized and regenerative medicine.

Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis

AIM:To investigate the role and potential mechanisms of bone marrow mesenchymal stem cells(MSCs) in severe acute peritonitis(SAP).METHODS:Pancreatic acinar cells from Sprague Dawley rats were randomly divided into three groups:nonsodium deoxycholate(SDOC) group(non-SODC group),SDOC group,and a MSCs intervention group(i.e.,a co-culture system of MSCs and pancreatic acinar cells + SDOC).The cell survival rate,the concentration of malonaldehyde(MDA),the density of superoxide dismutase(SOD),serum amylase(AMS) secretion rate and lactate dehydrogenase(LDH) leakage rate were detected at various time points.In a separate study,Sprague Dawley rats were randomly divided into either an SAP group or an SAP + MSCs group.Serum AMS,MDA and SOD,interleukin(IL)-6,IL-10,and tumor necrosis factor(TNF)-α levels,intestinal mucosa injury scores and proliferating cells of small intestinal mucosa were measured at various time points after injecting either MSCs or saline into rats.In both studies,the protective effect of MSCs was evaluated.RESULTS:In vitro,The cell survival rate of pancreatic acinar cells and the density of SOD were significantly reduced,and the concentration of MDA,AMS secretion rate and LDH leakage rate were significantly increased in the SDOC group compared with the MSCs intervention group and the Non-SDOC group at each time point.In vivo,Serum AMS,IL-6,TNF-α and MAD level in the SAP + MSCs group were lower than the SAP group;however serum IL-10 level was higher than the SAP group.Serum SOD level was higher than the SAP group at each time point,whereas a significant betweengroup difference in SOD level was only noted after 24 h.Intestinal mucosa injury scores was significantly reduced and the proliferating cells of small intestinal mucosa became obvious after injecting MSCs.CONCLUSION:MSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium,promote the proliferation of enteric epithelium and repair of the mucosa,attenuate systemic inflammation in rats with SAP.

Effect of poly(3-hydroxyalkanoates) as natural polymers on mesenchymal stem cells

Mesenchymal stem cells(MSCs)are stromal multipotent stem cells that can differentiate into multiple cell types,including fibroblasts,osteoblasts,chondrocytes,adipocytes,and myoblasts,thus allowing them to contribute to the regeneration of various tissues,especially bone tissue.MSCs are now considered one of the most promising cell types in the field of tissue engineering.Traditional petri dish-based culture of MSCs generate heterogeneity,which leads to inconsistent efficacy of MSC applications.Biodegradable and biocompatible polymers,poly(3-hydroxyalkanoates)(PHAs),are actively used for the manufacture of scaffolds that serve as carriers for MSC growth.The growth and differentiation of MSCs grown on PHA scaffolds depend on the physicochemical properties of the polymers,the 3D and surface microstructure of the scaffolds,and the biological activity of PHAs,which was discovered in a series of investigations.The mechanisms of the biological activity of PHAs in relation to MSCs remain insufficiently studied.We suggest that this effect on MSCs could be associated with the natural properties of bacteria-derived PHAs,especially the most widespread representative poly(3-hydroxybutyrate)(PHB).This biopolymer is present in the bacteria of mammalian microbiota,whereas endogenous poly(3-hydroxybutyrate)is found in mammalian tissues.The possible association of PHA effects on MSCs with various biological functions of poly(3-hydroxybutyrate)in bacteria and eukaryotes,including in humans,is discussed in this paper.

Current knowledge on the multiform reconstitution of intestinal stem cell niche

The development of“mini-guts”organoid originates from the identification of Lgr5+intestinal stem cells(ISCs)and circumambient signalings within their specific niche at the crypt bottom.These in vitro self-renewing“mini-guts”,also named enteroids or colonoids,undergo perpetual proliferation and regulated differentiation,which results in a high-performance,self-assembling and physiological organoid platform in diverse areas of intestinal research and therapy.The triumphant reconstitution of ISC niche in vitro also relies on Matrigel,a heterogeneous sarcoma extract.Despite the promising prospect of organoids research,their expanding applications are hampered by the canonical culture pattern,which reveals limitations such as inaccessible lumen,confine scale,batch to batch variation and low reproducibility.The tumor-origin of Matrigel also raises biosafety concerns in clinical treatment.However,the convergence of breakthroughs in cellular biology and bioengineering contribute to multiform reconstitution of the ISC niche.Herein,we review the recent advances in the microfabrication of intestinal organoids on hydrogel systems.

Lgr5^+ intestinal stem cell sorting and organoid culture

Intestinal epithelial stem cells (IESCs) are one of the most rapidly self‐renewing and proliferating adult stem cells. The IESCs reside at the bottom of intestinal and colonic crypts, giving rise to all intestinal epithelial lineages and maintaining intestinal epithelial replenishment. The technique of three‐dimensional culture based upon intestinal stem cell biology has been recently developed to study gastrointestinal development and disease pathogenesis. Here, we summarize the techniques used to isolate Lgr5‐ positive IESCs to form the enteroids from intestine or colonoids from colon, and present the means to examine these organoid functions. This study will provide a simple and practical way for producing intestinal tissues in the laboratory.

阻塞性睡眠呼吸暂停综合征患者认知障碍的研究进展

阻塞性睡眠呼吸暂停综合征(OSAS)主要通过慢性间歇性缺氧、睡眠结构紊乱以及分子生物学改变等机制导致认知障碍的发生。其认知障碍主要表现为记忆力、注意力、执行力等下降,并伴有日常生活活动能力的缺损。随着近年对OSAS监测和评估体系的逐渐成熟,针对OSAS治疗手段的研究已取得一定进展,但OSAS导致认知障碍的机制尚需进一步的研究证实。本文就OSAS认知功能障碍近年的研究进展予以综述。

能量代谢调控肠道干细胞功能研究进展及中医药治疗优势初探

肠道干细胞是维持肠道屏障功能稳定的一个重要部分,与肠道稳态、肠道上皮更新、肠道损伤的修复密切相关。人体正常生理活动离不开能量的摄入与代谢,干细胞的分化命运受能量代谢的影响,且肠道屏障受损与多种肠道疾病的发生发展有关。故本文以肠道干细胞为中心,以能量代谢及代谢物为背景,探究能量代谢及代谢物如何调控干细胞功能和活性,从而调节肠道屏障功能,为多种肠道疾病的治疗提供思路;此外,随着现代医学在保护肠道屏障方面研究的深入,中医讲求“顾护脾胃”的理论逐渐显示出科学性,以期为后续的研究提供思路。

经血源子宫内膜干细胞移植通过免疫调节缓解化疗引起的小鼠肠道损伤和菌群失调

目的:研究经血源子宫内膜干细胞(menstrual blood-derived endometrial stem cells,MenSCs)对化疗引起的小鼠肠道黏膜炎和菌群失调的治疗效果及潜在机制。方法:将小鼠随机分为正常组、顺铂(cisplatin,Cis)组和Cis+MenSC组,每组10只:Cis组和Cis+MenSC组小鼠采用腹腔注射Cis(2 mg·kg^(−1)·d^(−1),连续5 d)的方式建立小鼠化疗性肠黏膜炎模型,正常组小鼠经腹腔注射同等体积生理盐水;Cis+MenSC组小鼠经尾静脉移植MenSCs,而正常组与Cis组小鼠经尾静脉注射同等体积生理盐水。给药过程中观察小鼠体征及体重变化,实验结束后分离小鼠小肠、结肠部位,通过HE染色评估小鼠肠道组织形态学改变;免疫组化染色检测肠道组织中F4/80和IL-6阳性细胞率;Western blot检测肠道组织中肠道紧密连接蛋白、炎症因子及凋亡相关蛋白的变化;粪便微生物菌群16S rDNA扩增子测序检测小鼠肠道微生物群多样性和丰度的改变情况。结果:与Cis组小鼠相比,MenSCs移植组小鼠体重显著增加,HE染色显示小肠及结肠组织炎性细胞浸润减少,肠绒毛水肿减轻,腺体排列较有序;Western blot结果显示MenSCs移植可显著上调Cis损伤后小鼠肠道组织中紧密连接蛋白ZO-1和occludin的表达(P<0.05)。随后,免疫组化染色和Western blot结果显示MenSCs移植可显著降低Cis损伤后小鼠肠道组织中巨噬细胞数量(P<0.01),下调肠道组织中促炎因子IL-1β和IL-6和促凋亡蛋白Bax的表达(P<0.01);同时显著上调肠道组织中抑炎因子IL-10和抗凋亡相关蛋白Bcl-2的表达(P<0.01)。进一步粪便微生物测序结果显示,MenSCs移植可改善Cis诱导的肠道菌群失调,显著降低有害微生物艾森伯格氏菌(Eisenbergiella tayi)和人结肠厌氧棍状菌(Anaerotruncus colihominis)的丰度(P<0.01),同时显著增加肠道中有益微生物乳杆菌(Lactobacillus apodemi)的丰度(P<0.05),有助于恢复健康肠道菌群结构和功能。结论:MenSCs移植能够减轻化疗药物造成的小鼠肠道屏障损伤,减轻化疗相关小鼠黏膜炎的症状,有助于恢复肠道菌群稳态。