Peculiar Histopathological Alterations of Enterocytes in a Patient Co-infected with Severe Acute Respiratory Syndrome Coronavirus 2 and Mycobacterium Tuberculosis: A Case Study

The ongoing novel coronavirus disease 2019 (COVID-19) is principally defined by its respiratory symptoms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect the gastrointestinal tract (GIT) and although the pathogenesis of COVID-19 is understood, the exact pathological alterations following infection require further investigation. Here, we report our histopathological findings from a right hemicolectomy specimen from a patient coinfected with COVID-19 and Mycobacterium tuberculosis. Our observations showed that the novel SARS-CoV-2 can affect the GIT, causing epithelial injury and pathological alterations attributed to its ability to infect absorptive enterocytes by interacting with the angiotensin converting enzyme-2 (ACE2) receptor. These pathological findings are regarded as viral cytopathic changes and should be considered when evaluating gastrointestinal specimens from COVID-19-infected patients.

Peculiar Histopathological Alterations of Enterocytes in A Coronavirus Disease 2019 Patient with Mycobacterial Tuberculosis Co-Infection

Background: The ongoing novel Coronavirus Disease 2019 (COVID-19) pandemic is principally defined by its respiratory symptoms. While it is clear that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can affect the gastrointestinal tract (GIT) and the pathogenesis of coronavirus disease 2019 is better understood, the exact pathological alterations following infection require further investigation. The purpose of this paper is to report and share our histopathological findings from a right hemicolectomy specimen of a confirmed COVID-19 positive case, which exhibited a Mycobacterium Tuberculosis co-infection.Methods:Microscopic sections from right hemicolectomy specimen were appropriately stained and studied by two anatomical pathologists. Additionally, we searched PubMed and Google Scholar databases for reports/observations regarding pathological alterations of the intestine following COVID-19 infection.Results:Histological sections showed novel peculiar pathological alterations in the terminal ileal mucosa involving principally absorptive enterocytes with evidence of striking cellular injury as well as prominent erythrophagocytosis in the mesenteric lymph nodes. No specific pathological alterations were observed in the appendix or colon. The characteristic pathological features of Mycobacterium Tuberculosis infection were also observed throughout the specimen.Conclusions:Our observations showed that the novel SARS-CoV-2 can affect the gastrointestinal tract, causing epithelial injury and pathological alterations attributed to its ability to infect absorptive enterocytes by interacting with the Angiotensin Converting Enzyme-2 (ACE2) receptor. These pathological findings could be regarded as viral cytopathic changes and should be considered when evaluating gastrointestinal specimens from COVID-19 infected patients.

Gut Health and Immunity in Improving Poultry Production

A healthy gastro intestinal system is important for poultry to achieve its maximumproduction potential. This paper aims gut health and immunity to improve production in the poultry sector. Genetics, Nutrition and Bio security ate the factors influences the production. Gut consisting of various pH and micro biota throughout is an advantageous feature to prevent infections. Various components like Goblet cells, paneth cells, endocrine cells and absorptive enterocytes, tight junctions, GALT and Mucus play a major role in gut health. Balanced diet with optimum carbohydrates, proteins, amino acids, minerals, vitamins, enzymes, organic acids and good management practices are important for improving production. Alteration in supplementation essential amino acids, Zn, Vit E, Se … viz. are needed according to changes in environment and production state of the bird to develop good immunity. Stress free environment with fine hormonal balance are imperative for maximum output. Exploration of genes involved in resistant to food borne pathogens and research towards bio markers for gut health is the need of the hour. In can be concluded that good gut health and immunity play a key role in production. These can be achieved y maintaining birds with optimum nutrients and stress free environment.

Aberrant Epithelial Differentiation Contributes to Pathogenesis in a Murine Model of Congenital Tufting Enteropathy

Background & AimsCongenital Tufting Enteropathy (CTE) is an intractable diarrheal disease of infancy caused by mutation of Epithelial Cell Adhesion Molecule (EpCAM). The cellular and molecular basis of CTE pathology has been elusive. We hypothesized that the loss of EpCAM in CTE results in altered lineage differentiation and defects in absorptive enterocytes thereby contributing to CTE pathogenesis.MethodsIntestine from CTE mice was evaluated for specific markers by RT-qPCR, western blotting and immunostaining. Body weight, blood glucose and intestinal enzyme activity were also investigated. A CTE enteroid model was used to assess whether the decreased census of secretory cells could be rescued.ResultsCTE mice exhibited alterations in brush-border function, disaccharidase activity and glucose absorption, potentially contributing to nutrient malabsorption and impaired weight gain. Altered cell differentiation in CTE mice led to decreased secretory cells and increased numbers of absorptive cells, though the absorptive enterocytes lacked key features, causing brush border malfunction. Further, treatment with Notch signaling inhibitor, DAPT, increased the numbers of major secretory cell types in CTE enteroids (Graphical abstract 1).ConclusionsAlterations in intestinal epithelial cell differentiation in CTE mice favor an increase in absorptive cells at the expense of secretory cells. Although the proportion of absorptive enterocytes is increased, they lack key functional properties. We conclude that these effects underlie pathogenic features of CTE such as malabsorption and diarrhea, and ultimately the failure to thrive seen in patients. The ability of DAPT to reverse aberrant differentiation suggests a possible therapeutic strategy.SynopsisA murine model of Congenital Tufting Enteropathy exhibits altered intestinal cell differentiation, leading to increased absorptive and decreased secretory cells, which can be reversed with DAPT. Absorptive enterocytes in these mice are also dysfunctional, contributing to disease pathogenesis.Graphical Abstract

Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport

The ability to absorb ingested nutrients is an essential function of all metazoans and utilizes a wide array of nutrient transporters found on the absorptive enterocytes of the small intestine. A unique population of patients has previously been identified with severe congenital malabsorptive diarrhea upon ingestion of any enteral nutrition. The intestines of these patients are macroscopically normal, but lack enteroendocrine cells (EECs), suggesting an essential role for this rare population of nutrient-sensing cells in regulating macronutrient absorption. Here, we use human and mouse models of EEC deficiency to identify an unappreciated role for the EEC hormone peptide YY in regulating ion-coupled absorption of glucose and dipeptides. We find that peptide YY is required in the small intestine to maintain normal electrophysiology in the presence of vasoactive intestinal polypeptide, a potent stimulator of ion secretion classically produced by enteric neurons. Administration of peptide YY to EEC-deficient mice restores normal electrophysiology, improves glucose and peptide absorption, diminishes diarrhea and rescues postnatal survival. These data suggest that peptide YY is a key regulator of macronutrient absorption in the small intestine and may be a viable therapeutic option to treat patients with electrolyte imbalance and nutrient malabsorption.

Enteroendocrine cells couple nutrient sensing to nutrient absorption by regulating ion transport

SummaryThe ability to absorb ingested nutrients is an essential function of all metazoans and utilizes a wide array of nutrient transporters found on the absorptive enterocytes of the small intestine. A unique population of patients has previously been identified with severe congenital malabsorptive diarrhea upon ingestion of any enteral nutrition. The intestines of these patients are macroscopically normal, but lack enteroendocrine cells (EECs), suggesting an essential role for this rare population of nutrient-sensing cells in regulating macronutrient absorption. We used human and mouse models of EEC deficiency to identify a new role for the EEC hormone peptide YY in regulating ion-coupled absorption of glucose and dipeptides the small intestine. We found that peptide YY is required in to maintain normal electrophysiology in the presence of vasoactive intestinal polypeptide, a potent stimulator of ion secretion produced by enteric neurons. Administration of peptide YY to EEC-deficient mice restored normal electrophysiology, improved glucose and peptide absorption, diminished diarrhea and rescued postnatal survival. These data suggest that peptide YY is a key regulator of macronutrient absorption in the small intestine and may be a viable therapeutic option to treat patients with malabsorption.

Expression of plasmolemma proteins of the absorptive enterocytes of the cattle in the late fetal period

The article presents new scientific data on the expression of plasmalemma proteins of the absorptive enterocytes of the bovine intestines of five to nine months of age. In the late fetal period, 31 and 27 protein fractions of apical and basolateral membranes, respectively, were found in the plasmalemma of the jejunum intestine, which had a molecular weight of 9.6 kDa to 300 kDa. Twenty-nine protein fractions were detected in the apical membranes of five-month-old cattle enterocytes. It should be noted that protein fractions with low molecular weight (up to 24 kDa) were only 19.7 %, with molecular weights from 24 kDa to 100 kDa – 69.2 %, and fractions with molecular weights of 100 kDa and more were detected only – 11.1 % of the total number of polypeptides. Twenty-five protein fractions with a molecular weight of 9.6 to 155 kDa were found in the basolateral enterocyte membranes of five-month-old fetus. A large proportion of the detected protein fractions belonged to low molecular weight polypeptides (9.6–24 kDa – 40.26 %). Proteins with a molecular weight of 24–95 kDa – 55.2 %, with a molecular mass of 100 kDa and more were found only 4.56 %. High molecular weight proteins in the basolateral membrane of jejunum enterocytes of five-months-old cattle with a molecular weight greater than 155 kDa were not detected by electrophoresis (unlike the apical membrane). Analysis of the results of studies membranes protein of cattle enterocytes in late fetal period indicates significant changes in their polypeptide composition. In particular, in the basolateral membranes of enterocytes during the late fetal period there is a decrease in the content of low molecular weight protein fractions (3.3 times; P ≤ 0.001) and an increase in the proportion of high molecular weight. In addition, from the age of eight months, proteins with a molecular weight of 9.6–14.2 kDa and 75 kDa disappear in the basolateral membrane. Instead, proteins with a molecular weight of 300 kDa and 170-1885 kDa are appeared. In addition, in the apical membranes of enterocytes there is a significant decrease in the content of low molecular weight protein fractions and an increase in polypeptides with a molecular weight greater than 100 kDa. The appearance in the apical membranes of jejunum enterocytes of calves from eight months of age embryonic development of fractions of polypeptides with molecular weight of 24 kDa and 66 kDa, which are present until the end of the fetal period.

The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.

Genetically induced microtubule disruption in the mouse intestine impairs intracellular organization and transport

In most differentiated cells, microtubules reorganize into noncentrosomal arrays that are cell-type specific. In the columnar absorptive enterocytes of the intestine, microtubules form polarized apical–basal arrays that have been proposed to play multiple roles. However, in vivo testing of these hypotheses has been hampered by a lack of genetic tools to specifically perturb microtubules. Here we analyze mice in which microtubules are disrupted by conditional inducible expression of the microtubule-severing protein spastin. Spastin overexpression resulted in multiple cellular defects, including aberrations in nuclear and organelle positioning and deficient nutrient transport. However, cell shape, adhesion, and polarity remained intact, and mutant mice continued to thrive. Notably, the phenotypes of microtubule disruption are similar to those induced by microtubule disorganization upon loss of CAMSAP3/Nezha. These data demonstrate that enterocyte microtubules have important roles in organelle organization but are not essential for growth under homeostatic conditions.