Global collaboration is the cornerstone of scientific advancement.? Frontiers in Medicine has organized a series of special edition Research Topics, with the goal of highlighting the latest advancements in Gastroenterology across the globe, showcasing the academic excellence and high-quality work of internationally recognized researchers.? These collections aim to shed light on the recent progress made across the entire breadth of the Gastroenterology field and reflect on the future challenges faced by researchers across borders.?

Ain Shams University

Makerere University

University of Zambia

Faculty of Medicine, Minia University

Obafemi Awolowo University

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Frontiers in Medicine

Gastroenterology

Global Excellence in Gastroenterology: Africa

Africa is the world's second-largest and second-most populous continent, after Asia. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area and 20% of its land area (<a href="#B1">1</a>). With 1.4 billion people (<a href="#B2">2</a>, <a href="#B3">3</a>) as of 2021, it harbors about 18% of the world's human population. Africa's population is the youngest all over the world (<a href="#B4">4</a>).In the past, measurements of African health were not always accurate or representative. The African continent was home to a particularly diverse and deadly set of tropical diseases. Even in 2020, 96 percent of malaria deaths globally occurred within the African continent, with most fatalities occurring before the age of five in children (<a href="#B5">5</a>).Recently, the situation improved as the third United Nations Sustainable Development Goal 2030 (UN SDG 3) highlighted support of research and development of vaccines and medicines for communicable and non-communicable diseases that primarily affect developing countries, as it provide access to affordable essential medicines and vaccines, in accordance with the Doha Declaration on the TRIPS and Public Health, which affirms the right of developing countries to use the full provisions in the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) regarding flexibilities to protect public health, and, in particular, provide access to medicines for all (<a href="#B6">6</a>).The work on the UNSDG 3 in many African countries was reflected on many positive outputs in the African health sector which has included the recent introduction of an effective vaccine against childhood malaria, the rapid recovery of life expectancies due to AIDS drugs and substantial increases in health expenditure across the continent since 2000 (<a href="#B5">5</a>).On September 30th 2021, Frontiers in Medicine launched a special topic under the title “Global excellence in gastroenterology practice: Africa” to highlight recent progress achieved in Gastroenterology specialty in Africa. The topic received 11 manuscript submissions. Four manuscripts were rejected: Two manuscripts were rejected due to being non-related to the topic subject and the other two failed to have the endorsement of two reviewers to be published according to the standards of Frontiers in Medicine. The seven manuscripts accepted for publication include five research articles, one opinion article and one mini review article.In an original research on a cohort of Zambian children suffering from stunting non-responsive to nutritional support, <a href="https://doi.org/10.3389/fmed.2022.849677">Mulenga et al.</a> studied the small intestinal epithelial changes occurring in such disease. They performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined on electron microscopy. CLE demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes of environmental enteropathy: villus blunting, lamina propria and epithelial inflammation, and depletion of secretory cells. The use of the new imaging modality CLE and examining intestinal biopsies by morphometry and electron microscopy helped to reveal the secrets of children with stunting non-responsive to nutritional support which is a common disease in all developing countries. For all developing countries, it is estimated that 32 and 20% of children (&lt;5 years old) are under-height (height-for-age Z score &lt; −2) and under-weight (weight-for-age Z score &lt; −2) for age (<a href="#B7">7</a>).On the other hand, another research by <a href="https://doi.org/10.3389/fmed.2022.904339">Schillinger et al.</a> reported a new breath test using 13C-sucrose for the non-invasive assessment of environmental enteropathy in Zambian adults with promising results.The study included in the topic conducted by <a href="https://doi.org/10.3389/fmed.2022.927744">Dabbous et al.</a> at Ain Shams University, Cairo, Egypt addressed the risk factors and the management of biliary stones post living donor liver transplant and its effect on graft outcome. Biliary complications were previously reported in 39.0% post living donor liver transplantation (<a href="#B8">8</a>). <a href="https://doi.org/10.3389/fmed.2022.927744">Dabbous et al.</a> identified risk factors in both donors and recipients and proved that endoscopic management is the best option with the best results in those cases. They also proved that with precise and prompt management they could avoid morbidity and have similar survival rate as the control group.The reported prevalence of PHG varies from 3.7 to 75% in patients with portal hypertension and from 15.1 to 100% in patients with liver cirrhosis (<a href="#B9">9</a>).In the article of <a href="https://doi.org/10.3389/fmed.2022.902255">Alarfaj et al.</a> included in the current topic, the authors studied H. pylori infection in 80 Egyptian cirrhotic patients with portal hypertensive gastropathy (PHG) and 80 cirrhotic patients without PHG (controls) at Mansoura University Hospital, Mansoura, Egypt. They reported that the prevalence of H. pylori infection was significantly higher in patients with PHG (P &lt; 0.001). The severity of PHG was associated with H. pylori infection (P &lt; 0.001). They found that the response to eradication therapy of H. pylori infection was better in patients without PHG (P = 0.045).In the current topic, a basic research article from Egypt conducted by <a href="https://doi.org/10.3389/fmed.2022.903856">El Sobky et al.</a> documented the role of lnc RNA in causing de novo lipogenesis (DNL) and fat droplet accumulation in hepatocytes as a cause of non-alcoholic fatty liver disease (NAFLD). Their study showed for the first time the impact of miR-6155p and H19 on the mTOR/SREBP1c axis and its functional impact on lipid droplets and triglyceride accumulation in hepatocytes. These findings might pave the way for using ncRNAs as potential therapeutic targets in the management of fatty liver.In conclusion there is a great potential for high standard gastroenterology practice and research in Africa, as shown in the previously presented articles from the topic, provided that all unmet needs are addressed. The unmet needs include: Increasing funds to health care sectors, increasing research budgets in all African countries whether through the support of native governments or through international funding agencies support in an equitable manner, prioritization of research projects according to local needs, improvement of the documentation and establishing registries for malignant and other diseases, increasing collaborative research at local, regional, continental and international levels and lastly the Africans should aim high to publish high standard research in highly citable medical journals to keep in pace with the international standards.RE wrote the draft. PO, VK, YF, and OO reviewed the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Editorial: Global excellence in gastroenterology: Africa

Gastric adenocarcinoma (GCA) is the 5th leading cancer globally with an estimated 1.1 million cases reported in 2020. Ninety percent of non-cardia GCAs are attributable to Helicobacter pylori (H. pylori), the most prevalent bacterial infection globally. Rates of H. pylori infection are highest in Sub-Saharan Africa (SSA), yet surprisingly low numbers of GCAs are reported in the region. A similar phenomenon is seen with the inflammatory bowel diseases (IBD), Crohn’s disease, and ulcerative colitis. These disorders have risen dramatically over the past century in high income countries across the globe, with sharp increases noted more recently in newly industrialized regions. In contrast IBD is rare in most regions in SSA. For both diseases this may reflect under-reporting or limited access to diagnostic modalities, but an alternative explanation is the high burden of infection with gastrointestinal parasites endemic to SSA which may attenuate the risk of developing GCA and IBD. In this mini review we discuss the complex interplay between these microorganisms, GCA, and IBD, as well as a possible protective role of H. pylori and the development of IBD.

Gastric adenocarcinoma (GCA) is the 5th leading cancer globally with an estimated 1.1 million cases reported in 2020. Ninety percent of non-cardia GCAs are attributable to Helicobacter pylori (H. pylori), the most prevalent bacterial infection globally. Rates of H. pylori infection are highest in Sub-Saharan Africa (SSA), yet surprisingly low numbers of GCAs are reported in the region. A similar phenomenon is seen with the inflammatory bowel diseases (IBD), Crohn’s disease, and ulcerative colitis. These disorders have risen dramatically over the past century in high income countries across the globe, with sharp increases noted more recently in newly industrialized regions. In contrast IBD is rare in most regions in SSA. For both diseases this may reflect under-reporting or limited access to diagnostic modalities, but an alternative explanation is the high burden of infection with gastrointestinal parasites endemic to SSA which may attenuate the risk of developing GCA and IBD. In this mini review we discuss the complex interplay between these microorganisms, GCA, and IBD, as well as a possible protective role of H. pylori and the development of IBD.

The impact of Helicobacter pylori and intestinal helminth infections on gastric adenocarcinoma and inflammatory bowel disease in Sub-Saharan Africa

IntroductionIncreased de novo lipogenesis (DNL) is one of the key factors contributing to fat accumulation and non-alcoholic fatty liver disease (NAFLD). Among the critical transcription factors (TFs) regulating DNL is mTOR and its downstream lipogenic TF, SREBP1c. In recent years, it has been established that non-coding RNAs (ncRNAs) play role in both biological processes and disease pathogenesis. Our group has previously characterized microRNAs that can target and regulate the expression of both mTOR and SREBP1c. Accordingly, this study aimed to broaden our understanding of the role of ncRNAs in regulating the mTOR/SREBP1c axis to elucidate the role of the non-coding transcriptome in DNL and lipid droplet (LD) formation. Hence, short ncRNA, miR-615-5p, and long non-coding RNA (lncRNA), H19, were chosen as they were previously proven to target mTOR by our group and in the published literature, respectively.</sec>MethodologyHuh-7 cells were treated with 800 μM oleic acid (OA) to promote LD formation. Transfection of miR-615-5p mimics or H19 over-expression vectors was performed, followed by the measurement of their downstream targets, mTOR and SREBP, on the mRNA level by quantitative real-time PCR (qRT-PCR), and on the protein level by Western blot. To determine the functional impact of miR-615-5p and H19 on LD formation and triglyceride (TG) accumulation, post-transfection LDs were stained, imaged, and characterized, and TGs were extracted and quantified.</sec>ResultsmiR-615-5p was able to reduce mTOR and SREBP1c significantly on both the mRNA and protein levels compared to control cells, while H19 caused a reduction of both targets on the protein level only. Both miR-615-5p and H19 were able to significantly reduce the LD count and total area, as well as TG levels compared to control cells.</sec>ConclusionTo conclude, this study shows, for the first time, the impact of miR-615-5p and H19 on the mTOR/SREBP1c axis, and thus, their functional impact on LDs and TG accumulation. These findings might pave the way for using ncRNAs as potential therapeutic targets in the management of fatty liver.</sec>

Introduction: Increased de novo lipogenesis (DNL) is one of the key factors contributing to fat accumulation and non-alcoholic fatty liver disease (NAFLD). Among the critical transcription factors (TFs) regulating DNL is mTOR and its downstream lipogenic TF, SREBP1c. In recent years, it has been established that non-coding RNAs (ncRNAs) play role in both biological processes and disease pathogenesis. Our group has previously characterized microRNAs that can target and regulate the expression of both mTOR and SREBP1c. Accordingly, this study aimed to broaden our understanding of the role of ncRNAs in regulating the mTOR/SREBP1c axis to elucidate the role of the non-coding transcriptome in DNL and lipid droplet (LD) formation. Hence, short ncRNA, miR-615-5p, and long non-coding RNA (lncRNA), H19, were chosen as they were previously proven to target mTOR by our group and in the published literature, respectively.Methodology: Huh-7 cells were treated with 800 μM oleic acid (OA) to promote LD formation. Transfection of miR-615-5p mimics or H19 over-expression vectors was performed, followed by the measurement of their downstream targets, mTOR and SREBP, on the mRNA level by quantitative real-time PCR (qRT-PCR), and on the protein level by Western blot. To determine the functional impact of miR-615-5p and H19 on LD formation and triglyceride (TG) accumulation, post-transfection LDs were stained, imaged, and characterized, and TGs were extracted and quantified.Results: miR-615-5p was able to reduce mTOR and SREBP1c significantly on both the mRNA and protein levels compared to control cells, while H19 caused a reduction of both targets on the protein level only. Both miR-615-5p and H19 were able to significantly reduce the LD count and total area, as well as TG levels compared to control cells.Conclusion: To conclude, this study shows, for the first time, the impact of miR-615-5p and H19 on the mTOR/SREBP1c axis, and thus, their functional impact on LDs and TG accumulation. These findings might pave the way for using ncRNAs as potential therapeutic targets in the management of fatty liver.

Regulation of lipid droplet (LD) formation in hepatocytes via regulation of SREBP1c by non-coding RNAs

BackgroundBile stones are associated with numerous complications in liver transplant recipients. Endoscopic retrograde cholangiopancreatography (ERCP) has been proven to be safe and highly effective in dealing with most post-transplant biliary complications.</sec>ObjectiveThe objective of this study was to identify the possible risk factors for bile stone formation on top of biliary stricture, the effects of stones on graft outcomes, and their management.</sec>MethodsThis case–control study included 83 patients who underwent living donor liver transplant (LDLT) and suffered from postoperative biliary stricture with or without stones. Patients were divided into two groups. Group 1 (n = 55) included patients with biliary strictures with no stones and group 2 (n = 28) included patients who developed stones on top of biliary strictures. Data about the recipient and donor characteristics, surgical technique, blood lipid profile, immunosuppressive drugs, post-transplant complications, and interventions were collected from the medical records.</sec>ResultsThe frequency of hepatitis C virus (HCV) was significantly higher in group 2 compared to group 1 (71.4% vs. 47.3%, p = 0.036). The body mass index (BMI) of the donors was significantly higher in group 2 than in group 1 (25.17 ± 2.53 vs. 23.68 ± 2.63, p = 0.015). Episodes of acute rejection were significantly higher in group 2 than in group 1 (21.4% vs. 5.5%, p = 0.027). The ERCP was sufficient in most of the cases (89.2%) to ensure biliary drainage. The identified independent risk factors for biliary stones included HCV, biliary drain, donor's BMI, and serum cholesterol level.</sec>ConclusionPositive HCV, biliary drain insertion, donor's BMI, and serum cholesterol level were independent risk factors for developing bile stones on top of biliary strictures. Biliary stones were associated with high episodes of acute graft rejection, and they could be successfully managed by the ERCP modality.</sec>

Background: Bile stones are associated with numerous complications in liver transplant recipients. Endoscopic retrograde cholangiopancreatography (ERCP) has been proven to be safe and highly effective in dealing with most post-transplant biliary complications.Objective: The objective of this study was to identify the possible risk factors for bile stone formation on top of biliary stricture, the effects of stones on graft outcomes, and their management.Methods: This case–control study included 83 patients who underwent living donor liver transplant (LDLT) and suffered from postoperative biliary stricture with or without stones. Patients were divided into two groups. Group 1 (n = 55) included patients with biliary strictures with no stones and group 2 (n = 28) included patients who developed stones on top of biliary strictures. Data about the recipient and donor characteristics, surgical technique, blood lipid profile, immunosuppressive drugs, post-transplant complications, and interventions were collected from the medical records.Results: The frequency of hepatitis C virus (HCV) was significantly higher in group 2 compared to group 1 (71.4% vs. 47.3%, p = 0.036). The body mass index (BMI) of the donors was significantly higher in group 2 than in group 1 (25.17 ± 2.53 vs. 23.68 ± 2.63, p = 0.015). Episodes of acute rejection were significantly higher in group 2 than in group 1 (21.4% vs. 5.5%, p = 0.027). The ERCP was sufficient in most of the cases (89.2%) to ensure biliary drainage. The identified independent risk factors for biliary stones included HCV, biliary drain, donor's BMI, and serum cholesterol level.Conclusion: Positive HCV, biliary drain insertion, donor's BMI, and serum cholesterol level were independent risk factors for developing bile stones on top of biliary strictures. Biliary stones were associated with high episodes of acute graft rejection, and they could be successfully managed by the ERCP modality.

Risk factors and management of biliary stones after living donor liver transplant and its effect on graft outcome

ObjectivesEnvironmental enteropathy (EE) is a subclinical disorder highly prevalent in tropical and disadvantaged populations and is thought to play a role in growth faltering in children, poor responses to oral vaccines, and micronutrient deficiencies. This study aims to evaluate the potential of a non-invasive breath test based on stable isotopes for evaluation of impaired digestion and absorption of sucrose in EE.</sec>MethodsWe optimized a 13C-sucrose breath test (13C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the 13C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the 13C-SBT to intestinal mucosal morphometry, immunostaining for sucrose-isomaltase (SI) expression, and SI activity in 24 Zambian adults with EE.</sec>ResultsFully labeled sucrose (0.3 mg/kg) provided clear breath enrichment signals over 2–3 h in both British and Zambian adults, more than fivefold higher than naturally enriched sucrose. Reducose dramatically impaired 13C-sucrose digestion, reducing 4 h 13CO2 breath recovery by > 50%. Duodenal biopsies in Zambian adults confirmed the presence of EE, and SI immunostaining was present in 16/24 adults. The kinetics of 13CO2 evolution were consistently faster in participants with detectable SI immunostaining. Although sucrase activity was strongly correlated with villus height (r = 0.72; P < 0.05) after adjustment for age, sex and body mass index, there were no correlations between 13C-SBT and villus height or measured sucrase activity in pinch biopsies.</sec>ConclusionA 13C-SBT was developed which was easy to perform, generated clear enrichment of 13CO2 in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.</sec>

Objectives: Environmental enteropathy (EE) is a subclinical disorder highly prevalent in tropical and disadvantaged populations and is thought to play a role in growth faltering in children, poor responses to oral vaccines, and micronutrient deficiencies. This study aims to evaluate the potential of a non-invasive breath test based on stable isotopes for evaluation of impaired digestion and absorption of sucrose in EE.Methods: We optimized a 13C-sucrose breath test (13C-SBT) in 19 young adults in Glasgow, United Kingdom. In a further experiment (in 18 adults) we validated the 13C-SBT using Reducose, an intestinal glucosidase inhibitor. We then compared the 13C-SBT to intestinal mucosal morphometry, immunostaining for sucrose-isomaltase (SI) expression, and SI activity in 24 Zambian adults with EE.Results: Fully labeled sucrose (0.3 mg/kg) provided clear breath enrichment signals over 2–3 h in both British and Zambian adults, more than fivefold higher than naturally enriched sucrose. Reducose dramatically impaired 13C-sucrose digestion, reducing 4 h 13CO2 breath recovery by &gt; 50%. Duodenal biopsies in Zambian adults confirmed the presence of EE, and SI immunostaining was present in 16/24 adults. The kinetics of 13CO2 evolution were consistently faster in participants with detectable SI immunostaining. Although sucrase activity was strongly correlated with villus height (r = 0.72; P &lt; 0.05) after adjustment for age, sex and body mass index, there were no correlations between 13C-SBT and villus height or measured sucrase activity in pinch biopsies.Conclusion: A 13C-SBT was developed which was easy to perform, generated clear enrichment of 13CO2 in breath samples, and clearly reports sucrase activity. Further work is needed to validate it and understand its applications in evaluating EE.

13C-sucrose breath test for the non-invasive assessment of environmental enteropathy in Zambian adults

Hepatocellular Carcinoma in Africa: Challenges and Opportunities

The relationship between Helicobacter pylori (H. pylori) infection and Portal hypertensive gastropathy (PHG) is still a debatable matter. The aim of this study is to find out how common H. pylori infection is in cirrhotic patients with PHG and to see if there’s a link between H. pylori infection and PHG severity. Out of 340 cirrhotic patients who had upper Gastrointestinal Tract (GIT) endoscopy for early varices screening, 160 cirrhotic patients were selected and divided into 2 groups; 80 cirrhotic patients with PHG (cases) and 80 cirrhotic patients without PHG (controls). Gastric biopsies were taken from all enrolled patients for histological evaluation for the presence or absence of H. pylori infection. H. pylori was found in 44 cirrhotic patients (55%) who had PHG (cases), compared to 22 cirrhotic patients (27.5%) who did not have PHG (controls). The prevalence of H. pylori infection was significantly higher in patients with PHG (p < 0.001). The severity of PHG was associated with H. pylori infection (p < 0.001). The response to eradication therapy of H. pylori infection was must better in patients without PHG (p = 0.045). By multi-variant analysis, H. pylori infection, splenic diameter, and portal vein diameter were independent predictors for PHG presence. After treating H. pylori infection in patients who tested positive for H. pylori, there was a significant reduction in PHG severity (p < 0.001). Patients with PHG have a greater prevalence of H. pylori infection. PHG is more severe in patients infected with H. pylori. To improve PHG severity, cirrhotic patients must have their H. pylori infection eradicated.

The relationship between Helicobacter pylori (H. pylori) infection and Portal hypertensive gastropathy (PHG) is still a debatable matter. The aim of this study is to find out how common H. pylori infection is in cirrhotic patients with PHG and to see if there’s a link between H. pylori infection and PHG severity. Out of 340 cirrhotic patients who had upper Gastrointestinal Tract (GIT) endoscopy for early varices screening, 160 cirrhotic patients were selected and divided into 2 groups; 80 cirrhotic patients with PHG (cases) and 80 cirrhotic patients without PHG (controls). Gastric biopsies were taken from all enrolled patients for histological evaluation for the presence or absence of H. pylori infection. H. pylori was found in 44 cirrhotic patients (55%) who had PHG (cases), compared to 22 cirrhotic patients (27.5%) who did not have PHG (controls). The prevalence of H. pylori infection was significantly higher in patients with PHG (p &lt; 0.001). The severity of PHG was associated with H. pylori infection (p &lt; 0.001). The response to eradication therapy of H. pylori infection was must better in patients without PHG (p = 0.045). By multi-variant analysis, H. pylori infection, splenic diameter, and portal vein diameter were independent predictors for PHG presence. After treating H. pylori infection in patients who tested positive for H. pylori, there was a significant reduction in PHG severity (p &lt; 0.001). Patients with PHG have a greater prevalence of H. pylori infection. PHG is more severe in patients infected with H. pylori. To improve PHG severity, cirrhotic patients must have their H. pylori infection eradicated.

Helicobacter pylori Infection in Cirrhotic Patients With Portal Hypertensive Gastropathy: A New Enigma?

BackgroundEnvironmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen in vivo in adults and children with EE. We set out to identify epithelial lesions which might explain this phenomenon in Zambian children with stunting non-responsive to nutritional support.</sec>MethodsWe performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.</sec>ResultsConfocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes of EE: villus blunting, lamina propria and epithelial inflammation, and depletion of secretory cells (Paneth cells and goblet cells). Epithelial abnormalities included marked variability in epithelial height, disorganised and shortened microvilli, dilated intercellular spaces, pseudostratification, formation of synechiae between epithelium on adjacent villi, crypt destruction, and abundant destructive lesions which may correspond to the microerosions identified on CLE.</sec>ConclusionEpithelial abnormalities were almost universal in Zambian children with non-responsive stunting, including epithelial microerosions, cell-cell adhesion anomalies, and defects in secretory cells which may all contribute to impairment of mucosal barrier function and microbial translocation.</sec>

Background: Environmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen in vivo in adults and children with EE. We set out to identify epithelial lesions which might explain this phenomenon in Zambian children with stunting non-responsive to nutritional support.Methods: We performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.Results: Confocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes of EE: villus blunting, lamina propria and epithelial inflammation, and depletion of secretory cells (Paneth cells and goblet cells). Epithelial abnormalities included marked variability in epithelial height, disorganised and shortened microvilli, dilated intercellular spaces, pseudostratification, formation of synechiae between epithelium on adjacent villi, crypt destruction, and abundant destructive lesions which may correspond to the microerosions identified on CLE.Conclusion: Epithelial abnormalities were almost universal in Zambian children with non-responsive stunting, including epithelial microerosions, cell-cell adhesion anomalies, and defects in secretory cells which may all contribute to impairment of mucosal barrier function and microbial translocation.