Organ transplantation scandal influencing corneal donation rate

~ In the majority of countries, there is a shortage of donor corneas for corneal transplantations. This study investigated the impact of organ transplantation scandals on corneal donation rate at the University Hospital T/ibingen. Each deceased patient was considered as a potential corneal donor. An ophthalmic resident handled with stable methods of procedures the corneal donor procurement from 2009 to 2015. The rates of corneal donation were examined and analyzed. Among the 5712 hospital deaths, consent for corneal donation was obtained in 711 cases. The mean annual corneal donation rate was 12.4%. Since 2009, the donation rate per year could be increased with exception of 2013 and 2015. In the end of 2012 and 2014 two huge organ donation scandals were known in Germany. In the following years 2013 and 2015 corneal donation rate decreased significantly （P=0.0181 and P=0.0006）. We concluded that transplantation scandals have a significant impact on corneal donation rate. Improving professional＇s performance through full transparency and honesty is very important to earn trust of potential donors and their families.

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.

Effects of amniotic membrane transplantation on cytokines expression in chemically burned rat corneas

AIM: To investigate the effect of amniotic membrane transplantation (AMT) on the expressions of inflammatory-related, angiogenic-related and growth-related cytokines in rat corneas after chemical injury. METHODS: Alkali wounds were inflicted on the central corneas of rats by applying a round filter paper soaked in 1mol/L NaOH for 40 seconds. One week after alkali burn, 12 rats were randomly divided into 2 groups: the AMT group and the control group, and AMT was performed on the rats in the AMT group. Corneal opacity and neovascularization were observed by slit-lamp microscopy. The protein levels of interleukin (IL)-2, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta were determined by enzyme-linked immunosorbent assay 2 weeks after AMT. The mRNA levels of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were evaluated by real-time quantitative PCR. RESULTS: In the AMT group, the corneal opacity was improved (P =0.011) and the area of corneal neovascularization was significantly decreased (P=0.005) compared with the control group. The amount of IL-2 and IFN-gamma secreted by Th1 cells were decreased after AMT, whereas the amount of IL-10 and TGF-beta secreted by Th2 cells were increased ( P <0.05). The level of MMP-2 was significantly down-regulated (P=0.013) at the nnRNA level in the AMT group, while the expression of EGF was significantly higher (P= 0.022) compared with the control. CONCLUSION: AMT may suppress corneal neovascularization after chemical injury by modulating the expressions of soluble factors.

Corneal stem cells and tissue engineering: Current advances and future perspectives

Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there aremany challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed.

AB092.Database for the anatomopathological,functional and surgical characterization of the cornea

Background:The purpose of this infrastructure is to provide to the Network researchers a database and diverse related tools for the anatomical and functional analysis of the normal,pathological and surgical cornea.Methods:This database is composed of normal and pathological individuals,totaling more than 36,000 patients.It includes anatomical and functional imaging data,physiological optics data,psychometric and clinical data(medical history,surgical parameters,acuteness,etc.).Various corneal topography tools were added,giving the database a unique character:tools for analyzing individual maps,average map tools for the study and comparison of populations,3D modeling and visualization tools,statistical tools,etc.There are also screening tools for detecting various corneal conditions(LASIK,PRK,RK,keratoconus)and for secure data exchange between colleagues.Results:Several studies were made in recent years thanks to this common infrastructure.For example,this database has provided important information regarding the evolution of the 3D shape of the normal cornea with age and ametropia and has confirmed the mirror symmetry of corneas for the right and the left eyes(enantiomorphism).The different stages of Fuchs’dystrophy were also characterized to provide essential knowledge for surgery of the posterior layer of the cornea.Our database also allowed studying the anatomy of the wounds and the shape of the cornea before and after a transfixing transplant or an endothelial transplant(DSAEK and DSEK).The data on the characterization of experimentally transplanted corneas with corneal equivalents generated by tissue engineering and the recent addition of clinical data on the replacement of a diseased cornea with a synthetic corneal equivalent(keratoprosthesis)also resulted in several publications.More recently,the database has allowed to develop innovative algorithms to determine the optimal shape of an implant according to the clinical parameters of the recipient.On the other hand,we also demonstrated that the 3D shape of the cornea can be used as a biometric characteristic(such as fingerprints)for identification of individuals for various applications ranging from forensics to secure border crossings.Consequently,a new multimodal database(cornea+iris+eventually retina)was created for the purpose of biometric identifications.This database provides a unique set of anatomical and functional tools for the analysis of the cornea.It is characterized by the scientific quality and large quantity of accumulated information on the cornea and the high-level tools to exploit its content.Conclusions:The common infrastructure is easily accessible to all VHRN members on request.The database will also be accessible online in 2018(see http://cvl.concordia.ca for more information).

Expression of S100B during the innate immune of corneal epithelium against fungi invasion

AIM： To explore the expression of SIOOB in corneal epithelial cells under ,Aspergillus stimulation both in vivo and in vitro. METHODS： Immortalized human corneal epithelial cells （HCECs） were exposed to inactive #lsperg///us fumigatus （A. fumigatus） conidia at 0, 4, 8, 12, 16, and 24h respectively. The corneas of Wistar rats were exposed to active A. fumigatus at 0, 12, 24, 48h and the normal rat corneas were used for normal control. The mRNA level of S100B was evaluated by real time quantitative reverse transcription-polymerase chain reaction （qRT-PCR）. Sl00B protein expression in cornea epithelium was detected by immunohistochemical/immunocytochemical staining （IHC/ICC）. RESULTS： Histopathology revealed a significant inflammatory cell infiltration in fungal keratitis human and rat cornea. Corneal epithelial cells didn＇t express or rarely express S100B at baseline. A. fumigatus significantly induced S100B mRNA expression in cultured corneal epithelial cells in a time depended manner in vitro the mRNA began to rise significantly at 8h in vitro （P〈0.05） and continue to rise as time prolonged （P〈0.01）. in vivo S100B mRNA level was low in the normal corneas. However, it was increased in keratitis corneas from 12h after infection （P〈0.05） and reached to a peak at 24h （P〈0.001）. Immunochemistry revealed an obvious staining in fungal keratitis corneas as well as immortalized HCECs compared to the normal ones respectively, indicating an increased expression of SlOOB protein. CONCLUSION： S100B exists in corneal epithelial cells and is over-expressed under A. fumigatus stimulation. Sl00B may play an important role in the innate immune response of the corneal epithelium during A. fumigatus infection.

In situ cornea harvesting through the Red Cross Organization:a new approach to relieving severe cornea donor shortage in Chinese eye banks

Corneal diseases are currently the second main cause of blindness in China.Although most of the corneal blindness could be treated by corneal transplantation,only about 10 000 operations were carried out each year owing to the severe shortage of corneal donors and limited eye bank programs.A feasible cornea donation program was established through the organization of the Red Cross,and in situ corneal removal techniques were developed to avoid conflicts with Chinese traditions of keeping the deceased intact.The number of donated corneas,which had a safe and secure quality,increased significantly year by year.

Lymphangiogenesis Occurring in Transplanted Corneas

To study corneal lymphangiogenesis after corneal transplantation, corneal allogenic transplantation models were established in rats. 8 female Wister rats were used as donors, and 16 Sprague Dawley （SD） rats were used as recipients and 2 SD served as controls. Corneal lymphangiogenesis and hemangiogenesis was examined by electron microscopy 1 and 2 weeks after corneal penetrating transplantation, and the expression of lymphatic vessel endothelial receptor （LY- VE-1） was examined 1, 3, 7, 14 days after the transplantation respectively. In addition, 19 allograft failed human corneas were examined by 5＇-nase-alkaline phosphatase （5＇-NA-ALP） doubleenzyme-histochemistry staining to detect corneal lymphangiogenesis and hemangiogenesis. By immunohistochemistry for LYVE-1, it was found that blown lymphatics were localized in the stroma 3 days after the corneal transplantation. With electron microscopy, new lymphatic vessels and blood vessels were found 1 and 2 weeks after the corneal transplantation. By 5＇-NA-ALP enzyme-histochemistry, corneal hemangiogenesis was found in all allograft failed human corneas and 5 of 19 （26.3 % ） cases had developed corneal lymphangiogenesis. It is concluded that corneal lymphangiogenesis is present after corneal transplantation, which may play an important role in allograft rejection.

Limbal epithelial stem cells in corneal surface reconstruction

Cornea serves as the partial front barrier and major light reflection organ of the eye.The integrity of corneal surface is essential for ocular function.Injuries or congenital diseases could significantly destruct the homeostasis of the ocular surface,especially the microenvironment of limbal epithelial stem cells(LESCs),and will eventually cause dysfunction of corneal regeneration and diminish of LESCs.The loss of LESCs by different reasons are named limbal stem cell deficiency(LSCD),which is one of the leading cause of vision loss worldwide.To restore the corneal surface,LESC transplantation in the form of tissue or cell cultures is currently a viable and promising method to treat LSCD.In this review,we aim to introduce the characters and niche of LESCs,and discuss different aspects of its application in cornea surface reconstruction.

Studies on the Effects of the Immunosuppressant FK-506 on the High-risk Corneal Graft Rejection

Purpose: To evaluate the clinical efficacy of FK-506 on suppressing high-risk cornea transplantation rejection.Methods: In a randomized controlled clinical trial, 56 eyes of 56 patients with high-risk keratoplasty (including total corneal transplantation TCT, total corneal transplantation with circular lamellar sclera CST, vascularization corneal transplantation and corneal retransplantation) were divided into the experimental group and the control group(each with 28 eyes).The experimental group was treated by FK-506 eyedrops (0.5 mg/ml) and TobraDex eyedrops, compared with the control group that was treated by 1% CsA eyedrops and TobraDex eyedrops. In the average 8.1-month follow-up period, the visual acuity, graft transparent duration and Rejection Index (RI) of grafts were observed. Results: In the follow-up period, the graft rejection rate of the experimental and the control group was 63.6% and 95.2% respectively (χ2＝4. 72, P ＜ 0. 05) with significant difference.Conclusions: The local application of FK-506 suppressed effectively the graft rejection of corneal transplantation of the patients at high risk.

Transplantation of corneal stem cells cultured on amniotic membrane for corneal burn: experimental and clinical study

OBJECTIVE: To investigate the proliferation and differentiation of cultured corneal stem cells and determine the effect of corneal stem cells cultured on amniotic membranes on the limbal area for treating corneal burns. METHODS: The proliferation and differentiation of corneal stem cells in vitro had been examined using colony-forming efficiency and immunohistochemistry. The stem cells had been cultured on amniotic membranes and transplanted to the limbal area for treating corneal burns. RESULTS: Corneal stem cells had a high proliferation capacity in primary and first passage, cytokeratin 3 was not expressed in primary culture but partly in first passage. The stem cells could proliferate to form cell layer on an amniotic membrane. When transplanted, stem cells could survive on limbus. After transplantation, ocular inflammation resolved, the cornea re-epithelialized, the stromal opacity reduced, the superficial neovascularity was lessened and the conjunctival fornix re-established. CONCLUSIONS: Ocular surface conditions could be improved by allograft of corneal stem cells cultured on amniotic membranes.

Transplantation of human limbal cells cultivated on amniotic membrane for reconstruction of rat corneal epithelium after alkaline burn

BACKGROUND: The transplantation of limbal epithelial cells cultivated on amniotic membrane is a newly developed treatment for limbal stem cell deficiency. The purpose of our study was to investigate the biological characteristics of limbal epithelial cells and evaluate the effect of transplantation of cultivated human limbal epithelial cells on ocular surface reconstruction in limbal stem cell deficiency rat model. METHODS: Human limbal cells were isolated and cultivated in vitro. Cytokeratins 3, 12, and 19 (K3, K12 and K19) and p63 were detected by immunofluorescent staining or RT-PCR. BrdU labelling test was used to identify the slow cycling cells in the cultures. Limbal stem cell deficiency was established in rat cornea by alkali burn. Two weeks after injury, the rats received transplants of human limbal stem cells cultivated on amniotic membrane carrier. The therapeutic effect was evaluated by slit lamp observation, Hemotoxin and Eosin (HE) staining and immunofluorescent staining. RESULTS: On day 7 in primary culture, p63 and K19 were strongly expressed by most cells but only a few cells expressed K3. On days 14 and 21, p63 and K19 were still expressed by a majority of cells, but the expressive intensity of p63 decreased in a number of cells, while the proportion of K3 positive cells increased slightly and some cells coexpressed p63 and K3. RT-PCR showed that gene expression of both p63 and K12 were positive in cultivated limbal cells, but in mature superficial epithelial cells, only K12 was detected. BrdU labelling test showed that most cells were labelled with BrdU after 7 days' labelling and BrdU label retaining cells were observed after chasing for 21 days with BrdU free medium. For in vivo test, slit lamp observation, HE staining and immunofluorescent staining showed that the rats receiving transplant of human limbal stem cells cultivated on amniotic membrane grew reconstructed corneas with intact epithelium, improved transparency and slight or no neovascularization. A majority of epithelial cells of the reconstructed cornea were positive to antihuman nuclear antibody and cells expressing K3 were found mainly in superfacial epithelium. CONCLUSIONS: Limbal stem cells can be cultivated in vitro: the cells are characterized by high proliferation and slow cycling and identified as p63/K19 positive and K3/K12 negative. During culture, some stem cells can proliferate and differentiate into mature cornea epithelial cells. Amniotic membrane is a suitable carrier for limbal stem cells. Transplantation of human limbal stem cells cultivated on amniotic membrane can functionally reconstruct rat cornea with limbal stem cell deficiency.

Cellular therapy of the corneal stroma: a new type of corneal surgery for keratoconus and corneal dystrophies

Cellular therapy of the corneal stroma,with either ocular or extraocular stem cells,has been gaining a lot of interest over the last decade.Multiple publications from different research groups are showing its potential benefits in relation to its capacity to improve or alleviate corneal scars,improve corneal transparency in metabolic diseases by enhancing the catabolism of the accumulated molecules,generate new organized collagen within the host stroma,and its immunosuppressive and immunomodulatory properties.Autologous extraocular stem cells do not require a healthy contralateral eye and they do not involve any ophthalmic procedures for their isolation.Mesenchymal stem cells have been the most widely assayed and have the best potential to differentiate into functional adult keratocytes in vivo and in vitro.While embryonic stem cells have been partially abandoned due to ethical implications,the discovery of the induced pluripotent stem cells(iPSC)has opened a new and very promising field for future research as they are pluripotent cells with the capacity to theoretically differentiate into any cell type,with the special advantage that they are obtained from adult differentiated cells.Cellular delivery into the corneal stroma has been experimentally assayed in vivo in multiple ways:systemic versus local injections with or without a carrier.Encouraging preliminary human clinical data is already available although still very limited,and further research is necessary in order to consolidate the clinical applications of this novel therapeutic line.

Immunity phenomena following olfactory ensheathing cell transplantation into experimental allergic encephalomyelitis rat brain

Olfactory ensheathing cells （OECs） can promote axonal regeneration and remyelination for the treatment of spinal cord injury. OECs can also treat experimental allergic encephalomyelitis （EAE）, but it remains unclear whether OECs might be rejected by the immune system in the brain including the destruction of the blood-brain barrier under inflammation, the release of inflammatory factors, the activation of local antigen-presenting cells （e.g., microglia cells） and antigen drainage. We found that OECs expressed major histocompatibility complex （MHC）-I molecules on the cell surface, barely expressed MHC-II, but MHC-II could be induced by interferon-v, suggesting that OECs have certain immunogenicity. When OECs were transplanted into normal animal brains, no OECs were phagocytosed by dendritic cells in the cervical lymph node, and OECs did not induce lymphocyte proliferation, which indicates that OECs share some immune privilege under normal conditions. However, OECs in the rat EAE brain were phagocytosed by dendritic cells in the cervical lymph node and enhanced lymphocyte proliferation. These findings suggest that OECs are rejected because of increased immunogenicity in EAE brain, and that brain inflammation, in particular activated dendritic cells, may be a prerequisite for rejecting OECs.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis

Immune-related adverse events(irAEs)are complications of the use of immune checkpoint inhibitors(ICIs).ICI-associated gastritis is one of the main irAEs.The gastric microbiota is often related to the occurrence and development of many gastric diseases.Gastric microbiota adjustment may be used to treat gastric disorders in the future.Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis.Therefore,we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

Downstaging of advanced hepatocellular carcinoma followed by liver transplantation using immune checkpoint inhibitors:Where do we stand?

Liver transplantation(LT)in patients with hepatocellular carcinoma(HCC)and chronic liver disease(CLD)is limited by factors such as tumor size,number,portal venous or hepatic venous invasion and extrahepatic disease.Although previously established criteria,such as Milan or UCSF,have been relaxed globally to accommodate more potential recipients with comparable 5-year outcomes,there is still a subset of the population that has advanced HCC with or without portal vein tumor thrombosis without detectable extrahepatic spread who do not qualify or are unable to be downstaged by conventional methods and do not qualify for liver transplantation.Immune checkpoint inhibitors(ICI)such as atezolizumab,pembrolizumab,or nivolumab have given hope to this group of patients.We completed a comprehensive literature review using PubMed,Google Scholar,reference citation analysis,and CrossRef.The search utilized keywords such as'liver transplant','HCC','hepatocellular carcinoma','immune checkpoint inhibitors','ICI','atezolizumab',and'nivolumab'.Several case reports have documented successful downstaging of HCC using the atezolizumab/bevacizumab combination prior to LT,with acceptable early outcomes comparable to other criteria.Adverse effects of ICI have also been reported during the perioperative period.In such cases,a 1.5-month interval between ICI therapy and LT has been suggested.Overall,the results of downstaging using combination immunotherapy were encouraging and promising.Early reports suggested a potential ray of hope for patients with CLD and advanced HCC,especially those with multifocal HCC or branch portal venous tumor thrombosis.However,prospective studies and further experience will reveal the optimal dosage,duration,and timing prior to LT and evaluate both short-and long-term outcomes in terms of rejection,infection,recurrence rates,and survival.

Management of cytomegalovirus corneal endotheliitis

Background:Cytomegalovirus(CMV)can manifest as corneal endotheliitis in immunocompetent individuals.Early diagnosis is prudent to prevent endothelial cell loss,which could ultimately lead to corneal decompensation.CMV DNA was first detected in an eye with corneal endotheliitis in 2006;since then,clinical evidence from numerous case reports and case series have accumulated.Main text:In this narrative review,we identified several drugs,including ganciclovir,valganciclovir,and their combination in oral,intravenous,intravitreal,and topical forms in different concentrations,together with the judicious use of topical steroids,have reported variable success.There has yet to be any prospective comparative study evaluating the efficacy and safety of these assorted forms of treatment;clinical evidence is based on case reports and case series.CMV endotheliitis presenting with corneal edema can masquerade as other corneal diseases and thus poses a great challenge especially in post-keratoplasty eyes.Heightened awareness is needed before and after keratoplasty to start prompt prophylaxis and treatment.Conclusion:There is no consensus on the management of CMV endotheliitis.Further studies are much needed to elucidate the optimal treatment modality,regime,and duration in the treatment and prophylaxis of CMV endotheliitis.

Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment

AIM To investigate the impact of fecal microbiota transplantation(FMT) treatment on allergic colitis(AC) and gut microbiota(GM).METHODS We selected a total of 19 AC infants,who suffered from severe diarrhea/hematochezia,did not relieve completely after routine therapy or cannot adhere to the therapy,and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT,and GM composition was assessed for infants and donors using 16 S r DNA sequencing analysis.RESULTS After FMT treatment,AC symptoms in 17 infants were relieved within 2 d,and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to followup. During follow-up,one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16 S r DNA analysis in ten AC infants,most of them(n = 6) had greater GM diversity after FMT. As a result,Proteobacteria decreased(n = 6) and Firmicutes increased(n = 10) in post-FMT AC infants. Moreover,Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level,Bacteroides(n = 6),Escherichia(n = 8),and Lactobacillus(n = 4) were enriched in some AC infants after FMT treatment,but the relative abundances of Clostridium(n = 5),Veillonella(n = 7),Streptococcus(n = 6),and Klebsiella(n = 8) decreased dramatically.CONCLUSION FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.