Equine Colic Research Articles

Preliminary Functional Analysis of the Gut Microbiome in Colic Horses

The gut microbiome plays a critical role in maintaining horse health, influencing digestion, immunity, and overall well-being. However, in certain conditions like colic, there is evidence of significant alterations in the microbial community. To analyze the composition of the fecal microbiome and the enriched predicted metabolic functions of horses with colic compared to a control group, 14 horses with colic and 14 control horses were recruited. From a stool sample, DNA extraction was carried out for subsequent 16S rRNA metagenomic analysis. The composition of the microbiome was analyzed from the sequences of each sample using the QIIME version 1.8.0 and DADA2 version 1.22 programs. PICRUSt2 was used to predict metabolic functions. Statistical analyses were performed with the Mann–Whitney U test from the Python scipy v1 package. The gut microbiomes of both groups were dominated by Firmicuteota, Bacteroidota, and Pseudomonadota phyla. Colic in horses was associated with reduced diversity, reduced abundance of Fibrobacter, and an increase in Streptococcus. The abundance of Firmicuteota was negatively correlated with Pseudomonadota and Actinobacteriota. The equine colic microbiome was predicted to be enriched in aerobic respiration pathways and fatty acid and amino acid degradation. These observations indicate discrete but important differences in the gut microbiome of colic horses.

Assessment of equine intestinal epithelial junctional complexes and barrier permeability using a monolayer culture system.

Gastrointestinal disease is a leading cause of death in mature horses. A lack of in vitro modeling has impeded the development of novel therapeutics. The objectives of this study were to develop and further characterize a small intestinal monolayer cell culture derived from equine jejunum including establishing normal measurements of intestinal permeability and restitution. Three-dimensional enteroids, derived from postmortem sampling of equine jejunum, were utilized to develop confluent epithelial monolayers. The presence of differentiated intestinal epithelial cell types and tight junctions were confirmed using histology, reverse transcription PCR (RT-PCR), RNAscope, protein immunofluorescence and transmission electron microscopy. Transepithelial resistance (TER) and macromolecule flux were assessed as measurements of paracellular and transcellular permeability. Scratch assays were utilized to model and assess intestinal restitution. Monolayer cell cultures reached 100% confluency by ~5-7 days. Equine jejunum monolayers were confirmed as epithelial in origin, with identification of differentiated intestinal epithelial cell types and evidence of tight junction proteins. Function of the intestinal barrier was supported by acquisition of physiologically normal TER values (179.9 ± 33.7 ohms*cm2) and limited macromolecule flux (22 ± 8.8% at 60 min). Additionally, following a scratch wound, epithelial cell monolayers migrated to close gap defects within 24 h. In conclusion, this study describes the development of a novel intestinal epithelial monolayer cell culture for equine jejunum, and provides evidence of intestinal epithelial cell differentiation, formation of physiologically relevant barrier function and use as a model of intestinal restitution to test potential therapeutics for equine colic.

Equine Enteric Glial Culture and Application to the Study of a Neural Inflammatory Mechanism in Equine Colic.

Inflammatory postoperative conditions of equine colic (acute abdomen) contribute not only to increased client cost, patient discomfort, and hospitalization time, but in many cases, prove to be life-threatening. A unique population of intestinal cells, enteric glia, are increasingly acknowledged for their roles in sensing the gastrointestinal environment and communicating with surrounding cell types. Interactions between enteric glia and intestinal epithelia may prove critical in establishing how equine enteric glia can alter the mucosal barrier to modulate inflammation in health and colic. To study this interaction, we present a method of establishing primary equine enteric glial cultures from equine jejunum and exposing the cultures to inflammatory conditions known to be present in colic. Primary enteric glial cultures were obtained from adult horses euthanized for reasons unrelated to colic. Intestinal villi and lamina propria were micro-dissected to expose the submucosa. The isolated submucosa underwent enzymatic digestion with collagenase, protease, and bovine serum albumin for 2-3 h. Next, mechanical digestion involving centrifugation, pipetting, and cell strainers (40-100 µm), yielded a pellet used for plating on 0.05 mg/mL poly-L-lysine-coated wells at a concentration of ~400,000 cells/300 µL of media. Following confluence and first passage, the enteric glial cells were then exposed to equine recombinant IL-1β (0, 10, 25 ng) for 24 h. To model epithelial-glial interactions at the time of colic, medium conditioned by either control or treated enteric glia was added directly to confluent equine jejunal monolayers while measuring transepithelial electrical resistance (TEER) using a dual-electrode EndOhm chamber. These data demonstrate just one of many potential impactful applications of equine enteric glial culture.

Large-scale study of blood markers in equine atypical myopathy reveals subclinical poisoning and advances in diagnostic and prognostic criteria

Equine atypical myopathy (AM) is a severe rhabdomyolysis syndrome primarily caused by hypoglycin A (HGA) and methylenecyclopropylglycine protoxins. This study aimed to refine diagnostic and prognostic criteria for AM while exploring apparently healthy cograzers. Blood samples from 263 horses, including AM cases (n= 95), cograzers (n= 73), colic horses (n= 19), and controls (n= 76), were analyzed for HGA, its toxic metabolite, and acylcarnitines profile. Diseased horses exhibited alterations in acylcarnitines that strongly distinguished them from controls and colic horses. Regression analyses identified distinct acylcarnitines profiles among groups, with cograzers showing intermediate alterations. Age and gelding status emerged as protective factors against AM. Furthermore, serum acylcarnitines profiling was valuable in predicting AM survival, with isovaleryl-/2-methylbutyrylcarnitine (i.e., C5 acylcarnitine) showing promise as both a diagnostic and prognostic marker. Subclinical alterations in cograzers underscore a novel aspect: the presence of subclinical cases of AM.

IL‐1β‐stimulated equine enteric glial media reduces equine enterocyte barrier function as a neural inflammatory mechanism in equine colic

<scp>IL</scp>‐1β‐stimulated equine enteric glial media reduces equine enterocyte barrier function as a neural inflammatory mechanism in equine colic

Qualitative study exploring the barriers and facilitators to the prevention and management of equine colic in working equid communities in Colombia

Qualitative study exploring the barriers and facilitators to the prevention and management of equine colic in working equid communities in Colombia

Evaluation of an educational intervention aimed to improve the prevention and management of equine colic in working equid populations in Colombia

Evaluation of an educational intervention aimed to improve the prevention and management of equine colic in working equid populations in Colombia

Presurgical radiographic visualization of colonic displacement in horses suspected of sand impaction colic

Presurgical radiographic visualization of colonic displacement in horses suspected of sand impaction colic

UK horse owners and veterinary practitioners' experiences of decision-making for critical cases of colic.

The survival of horses diagnosed with critical colic (requiring referral or euthanasia) relies on rapid and effective decision-making by the owner and veterinary practitioner. To explore UK horse owners' and veterinary practitioners' experiences of decision-making for critical cases of equine colic. Qualitative study using a phenomenological approach. Individual, semi-structured telephone interviews were conducted with 14 horse owners and 13 veterinary practitioners (vets) who had experienced a critical decision (referral or euthanasia) for a horse with colic. A purposive, convenience sample of participants was recruited. Sessions explored participant's experience of colic, including recognition, help-seeking behaviour, and challenges. Thematic analysis was performed on collected data. Four over-arching themes were identified; 'head', 'heart', 'practicalities' and 'impact'. Owners acknowledged responsibility for their horse's welfare but had different perspectives than vets on the importance of finance ('head'). Both vets and owners described how the horse-human relationship ('heart') often led to conflict during decision-making. The vet-client relationship was influential on decision-making for both owners and vets; involving other people in decision-making was described both positively and negatively by participants ('heart'). 'Practicalities', such as lack of preparedness, transport issues and adverse weather conditions, were identified by both owners and vets as barriers. Owners described a 'rollercoaster' of emotions after a critical decision, with profound impacts on their mental wellbeing, feelings of guilt, and long-term changes in behaviour ('impact'), and a lack of support to manage these feelings. Small sample size. This study describes stakeholder decision-making during critical cases of equine colic. Factors that commonly influenced decisions included an owner's previous knowledge and beliefs, social pressures, logistics and the relationship between the owner and vet. The study highlighted long-term impacts on the owner, including their management and decisions for subsequent horses. These factors should be considered in shared decision-making.

A Case of Severe Abomasal Sand Impaction in a Farmed White-Tailed Deer (Odocoileus virginianus) in Florida.

The University of Florida's Cervidae Health Research Initiative (CHeRI) conducted a post-mortem examination of a two-year-old white-tailed doe deceased at a northern Florida white-tailed deer farm. The carcass of the deer had notable emaciation and bloating. Upon opening of the carcass, there was pneumonia and the rumen was tympanic and enlarged. Additionally, the abomasum was distended and contained approximately 5 kg of sand. It is not uncommon for white-tailed deer to engage in geophagia (eating soil or sand), which typically does not result in diseases or fatalities. However, in this animal, we suspect a chronic process that created a physical barrier, hindering nutrient absorption and resulting in physical irritation of the abomasal mucosa with subsequent inflammation. This may have caused a disturbance in immune system function, allowing opportunistic bacteria to colonize and invade other organs, such as the lungs, contributing to the animal's death.

Comparison of transrectal and transabdominal transducers for use in fast localized abdominal sonography of horses presenting with colic.

Abdominal ultrasonography is valuable in the diagnosis of equine colic. Fast localized abdominal sonography of horses (FLASH) enables practitioners with limited experience to perform ultrasonography in emergency settings. However, many practitioners only possess rectal format linear array transducers (RFLT). The hypotheses are: (a) A low frequency curvilinear transducer (LFCT) and RFLT will detect free abdominal fluid and abnormal small intestinal loops with similar frequency during FLASH, and (b) there will be a difference between the transducers for detection of gastric abnormalities and nephrosplenic entrapment. The objective is to compare transcutaneous abdominal ultrasonographic detection of abnormalities in horses presenting with colic using a LFCT and RFLT. Twenty-four horses requiring FLASH for investigation of colic were enrolled. Horses that were too painful to undergo transcutaneous abdominal ultrasonographic examination were excluded. A single investigator performed FLASH on all horses using a RFLT, while one of three other clinicians simultaneously performed FLASH using a LFCT. Comparison of abnormal findings between the two transducers was performed using Chi square, Fisher's exact or Wilcoxon tests. The incidence of identification of abnormal findings was similar between the two transducers for all comparisons except the visibility of the left kidney and stomach (kidney LFCT 81.25% vs. RFLT 22.92%, stomach LFCT 87.5% vs. RFLT 62.5%). While there are limitations to using a RFLT to identify nephrosplenic entrapment of the colon and detection of the stomach, it reliably detects other common abnormalities, including peritoneal effusion, lesions of the small intestine, and changes to the wall of the large colon and cecum.

Depraved appetite in dromedary camels: Clinical, ultrasonographic, and postmortem findings.

Camels are subjected to a wide variety of nutritional deficiencies as they are largely dependent upon grazing desert plants. As a consequence, the syndrome of pica or depraved appetite is occasionally seen in dromedary camels. The condition is manifested as chewing or eating abnormal things such as wood, dirt, bones, stones, clothes, plastics, mud, sand, or other inanimate objects. This study was designed to investigate the clinical, ultrasonographic, and postmortem findings in dromedary camels with pica or depraved appetite. Twenty-five camels of 5 days to 15 years were examined. Owner complaints included depraved appetite, loss of body condition, regurgitation of stomach content, and partial or complete absence of feces. Symptoms described were present for a period varying between 3 days, up to 12 months. The stomach compartments and small and large intestines were scanned using ultrasonography from the right and left sides of the abdomen. Necropsy was carried out on six female and three male camels where the thoracic and abdominal organs were examined with special attention to the digestive system. The affected animals had a history of gradual loss of body conditions, eating foreign objects, decreased or total absence of feces, and regurgitation of stomach content. Using ultrasound, the foreign body was imaged occluding completely or partially the intestines. Foreign bodies within the rumen could not be visualized with ultrasound. In cases where the rumen is impacted by sand, small pin-points revealing acoustic enhancement were imaged. Foreign bodies were removed from the rumen at exploratory rumenotomy (n = 11), laparotomy (n = 3), or at necropsy (n = 8) in the form of plastics, cloths, sand, mud, wool balls, robes, glasses, or even metallic objects which may be blunt or sharp. Sixteen (64%) of the camels were recovered while the remaining 9 (36%) did not survive. The syndrome of pica or depraved appetite is an important condition in dromedary resulting in the ingestion of objects other than normal feed. Substantial economic losses are expected as a result of this syndrome. Ultrasonography of the digestive system may help the clinician in some cases to localize of occluding foreign bodies in the intestines, while in the transabdominal scanning of the stomach is valuable only in cases of sand impaction.

Evaluation of substance P as a biomarker for pain in equine colic

Equine colic is an important condition associated with acute abdominal pain and one of the leading causes of death in horses. As such, objectively evaluating pain is of interest for attending veterinarians. Pain scales for assessment are present, but no single pain-specific biomarker has been reported. The aim of this study was to determine if substance P (SP) could be a reliable biomarker to reflect pain and serve as a parameter to predict outcome in equine colic. The hypothesis was that horses displaying severe colic signs present with higher values of SP in contrast to those with mild colic signs. Thirty warmblood horses, aged between 3 and 20 years were recruited; evenly distributed (10 horses each) in three colic groups (mild, moderate, severe). To classify the colic signs, the horses were graded by the Equine Acute Abdominal Pain Scale (EAAPS). Clinical examination and EAAPS were performed at arrival in the hospital. Blood samples were collected four times in hourly intervals commencing from arrival. For comparison, already established parameters for prognosticating equine colic (heart rate, serum cortisol, and blood lactate concentration) were also measured. The assumption of increasing SP concentrations along with pain could not be confirmed. SP did not show any association with heart rate, cortisol, lactate, or EAAPS. Whereas the established parameters increased according to the EAAPS, SP remained stable in individual horses regardless of clinical signs, treatment, and disease progression. Consequently, SP was not a reliable parameter to reflect painful conditions or to predict outcome in equine colic.

Antibiotic prophylaxis and hospitalization of horses subjected to median laparotomy: gut microbiota trajectories and abundance increase of Escherichia.

Horse clinics are hotspots for the accumulation and spread of clinically relevant and zoonotic multidrug-resistant bacteria, including extended-spectrum β-lactamase producing (ESBL) Enterobacterales. Although median laparotomy in cases of acute equine colic is a frequently performed surgical intervention, knowledge about the effects of peri-operative antibiotic prophylaxis (PAP) based on a combination of penicillin and gentamicin on the gut microbiota is limited. We collected fecal samples of horses from a non-hospitalized control group (CG) and from horses receiving either a pre-surgical single-shot (SSG) or a peri-operative 5-day (5DG) course of PAP. To assess differences between the two PAP regimens and the CG, all samples obtained at hospital admission (t0), on days three (t1) and 10 (t2) after surgery, were screened for ESBL-producing Enterobacterales and subjected to 16S rRNA V1-V2 gene sequencing. We included 48 samples in the SSG (n = 16 horses), 45 in the 5DG (n = 15), and 20 in the CG (for t0 and t1, n = 10). Two samples of equine patients receiving antibiotic prophylaxis (6.5%) were positive for ESBL-producing Enterobacterales at t0, while this rate increased to 67% at t1 and decreased only slightly at t2 (61%). Shannon diversity index (SDI) was used to evaluate alpha-diversity changes, revealing there was no significant difference between horses suffering from acute colic (5DG, SDImean of 5.90, SSG, SDImean of 6.17) when compared to the CG (SDImean of 6.53) at t0. Alpha-diversity decreased significantly in both PAP groups at t1, while at t2 the onset of microbiome recovery was noticed. Although we did not identify a significant SDImean difference with respect to PAP duration, the community structure (beta-diversity) was considerably restricted in samples of the 5DG at t1, most likely due to the ongoing administration of antibiotics. An increased abundance of Enterobacteriaceae, especially Escherichia, was noted for both study groups at t1. Colic surgery and PAP drive the equine gut microbiome towards dysbiosis and reduced biodiversity that is accompanied by an increase of samples positive for ESBL-producing Enterobacterales. Further studies are needed to reveal important factors promoting the increase and residency of ESBL-producing Enterobacterales among hospitalized horses.

A review on equine colic: Etiology, differential diagnosis, therapy, and prevention

Equines encompass various animals, such as horses, donkeys, ponies, mules, and zebra. These animals are means of transportation, leisure, source of meat, and income worldwide. Equine colic is among the equines' most important, common, and emergent health issues, particularly in horses. The complexity and anatomical characteristics rendered equines prone to equine colic. Different classifications for equine colic are known depending on cause, affected site, and duration. In the current study, we have exhaustively focused on etiological, clinical findings, clinical and laboratory diagnosis, and eventually, the treatment and control of equine colic. Such knowledge is lacking, and some reports discuss only one or few aspects. Because they are the most prevalent cause, we have focused on gastrointestinal disorders as a cause of colic. Moreover, recent approaches for diagnosis and prognosis were investigated mainly via the biomarkers analysis assay. Because of its importance, similarity to other equines, worldwide distribution, and plenty of available research, we mostly specified our description of horses as a model of equine animals. This review offers valuable insights for veterinarians and equine practitioners, potentially aiding in mitigating health risks and fatal consequences associated with colic in equines

Arterial Blood Gas, Electrolyte and Acid-Base Values as Diagnostic and Prognostic Indicators in Equine Colic.

The study aimed to investigate if arterial blood analysis in conscious horses presenting with signs of colic and breathing ambient air had diagnostic or prognostic value. Arterial blood samples from 352 horses presenting with colic at a university equine referral hospital were analysed for pH, partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), concentrations of sodium (Na+), potassium (K+), ionised calcium (Ca2+) and chloride (Cl-), actual and standardised plasma bicarbonate concentration (HCO3- (P) and HCO3- (P, st)), blood and extracellular fluid base excess (Base (B) and Base (ecf)) and anion gap (AG). Results were compared to previously reported values for healthy horses, and comparisons were made between final diagnosis, treatment and survival to hospital discharge. Significant differences were found between colic cases and healthy reference values between some primary aetiologies. Overall, surgical and non-surgical colic cases differed in Ca2+ and Cl- concentrations and Ca2+ differed between cases that survived to discharge and those that did not. PaO2 differed between small intestinal surgical cases that survived and those that did not. From these results, we developed regression models that demonstrated excellent or good predictive value in identifying the likelihood of surgical versus medical management and survival to hospital discharge.

Incidence, risk factors, and therapeutic management of equine colic in Lamongan, Indonesia.

Colic is among the common health issues in equine health management. Gastrointestinal (GI) disorders are the most frequent causes of colic, but dysfunction of other organs and systems inside the abdominal cavity may also contribute. Therefore, it is crucial to identify risk factors for colic of specific etiologies. This study aimed to examine the incidence, risk factors, and best therapeutic management practices for horses with colic. A cohort of 256 horses living in Lamongan, East Java, Indonesia, was randomly recruited based on reports of colic symptoms by owners. Diagnosis and treatment were then conducted with the help of owners. Symptom profiles, risk factors, and therapeutic management strategies were analyzed by Chi-square tests. Of 256 horses enrolled, 217 (84%) were diagnosed with colic, of which 172 (79.3%) were cases of spasmodic colic, 33 (15.2%) of impaction colic, and 12 (5.5%) of intestinal obstruction/displacement. Male sex (χ2 = 16.27; p < 0.001), wheat bran feeding (χ2 = 15.49; p < 0.001), concentrate feed intake >5 kg/day (χ2 = 24.95; p < 0.001), no regular anthelmintic drug treatment (χ2 = 67.24; p < 0.001), GI parasite infection (χ2 = 65.11; p < 0.001), recurrent colic (χ2 = 91.09; p < 0.001), poor body condition score (χ2 = 71.81; p < 0.001), limited daily water access (χ2 = 127.92; p < 0.001), and indications of dental disease (χ2 = 9.03; p < 0.001) were identified as risk factors. The most effective therapies were gastric intubation (χ2 = 153.54; p < 0.001), Vitamin B complex injection (χ2 = 32.09; p < 0.001), fluid therapy (χ2 = 42.59; p < 0.001), and non-steroidal anti-inflammatory drug injection (NSAID). Colic is highly prevalent among horses in Lamongan, East Java, Indonesia. Proper diet, workload management, regular access to clean drinking water, and dental care can reduce colic risk. Recommended therapies include NSAID injection without other analgesics or spasmolytics, fluid therapy, Vitamin B complex, and gastric intubation.

116 Incidence of colic and lunar phase

Equine colic is defined as pain in the abdominal cavity; the etiology is commonly gastrointestinal. There is no known definitive cause, but conditions such as poor forage, poor dentition, parasites, or reduced water intake increase the risk of colic. Previous research on a small scale showed there is a weak but significant increase in the incidence of colic with the waxing gibbous and full moon. The objective of this study was to determine if the association between the incidence of colic and lunar phase was repeatable on a larger scale. Data on yearly equine admissions from Marion duPont Scott Equine Medical Center (2133 admissions) and Cornell University College of Veterinary Medicine Equine Hospital (1429 admissions) was aggregated, and the number of daily colic diagnoses was standardized into the number of daily colic diagnoses per 1000 yearly hospital admissions. Referred colic cases were confirmed by attending veterinarians. The corresponding moon phases were distributed into 3 levels: new moon + 2 d (n = 480), full moon + 2 d (n = 470) and remaining normal days (n = 1,850) and for each phase, the mean number of daily colic diagnoses per 1000 yearly admissions was foundto be 0.294 (SD = 0.478), 0.290 (SD = 0.463) and 0.304 (SD = 0.486), respectively. A priori power analysis showed the sample size was adequate to test the hypothesis (Statistical Power = 80%, α = 0.05). The data were strongly right skewed with multiple outliers, driving the decision to use the median and interquartile range (IQR) to represent the measure of center and dispersion and a Kruskal-Wallis H test for statistical analysis. The distribution of the number of colic cases per day were similar across all moon phases, as assessed by visual inspection of comparative boxplots. For all 3 lunar phases, the median number of daily colic diagnoses per 1000 yearly hospital admissions was 0 (IQR = 0.47). At the 0.05 significance level, there were no significant differences found in the median number of daily diagnoses per 1000 yearly admissions among the 3 lunar phases (χ2(2) = 0.261, P = 0.878). In conclusion, this data does not find an association between the incidence of referred colic cases and lunar phase.

Biomarkers of Intestinal Injury in Colic.

Biomarkers are typically proteins, enzymes, or other molecular changes that are elevated or decreased in body fluids during the course of inflammation or disease. Biomarkers pose an extremely attractive tool for establishing diagnoses and prognoses of equine gastrointestinal colic, one of the most prevalent causes of morbidity and mortality in horses. This topic has received increasing attention because early diagnosis of some forms of severe colic, such as intestinal ischemia, would create opportunities for rapid interventions that would likely improve case outcomes. This review explores biomarkers currently used in equine medicine for colic, including acute phase proteins, proinflammatory cytokines, markers of endotoxemia, and tissue injury metabolites. To date, no single biomarker has been identified that is perfectly sensitive and specific for intestinal ischemia; however, L-lactate has been proven to be a very functional and highly utilized diagnostic tool. However, further exploration of other biomarkers discussed in this review may provide the key to accelerated identification, intervention, and better outcomes for horses suffering from severe colic.

138 Age-Dependent Intestinal Barrier Repair in Suckling Pigs: A Comparative Model to Improve Neonatal Gastrointestinal Health Across Species

Abstract As in porcine epidemic diarrhea virus, strangulating equine colic or necrotizing enterocolitis in human infants, intestinal diseases involving ischemic injury cause mucosal barrier damage and are associated with poorer survival in neonates. The cause of age-dependent outcomes in afflicted individuals has not been fully explained and therefore novel preventatives and treatments are lacking. While traditional rodent models have not demonstrated age-dependent differences in intestinal recovery, our translational pig model is the first to demonstrate an age-dependent intestinal barrier repair defect. We have shown that, while weaned pigs recover rapidly after ischemic intestinal injury, barrier repair is markedly impaired in suckling pigs, due to complete failure of epithelial restitution. Importantly, we found that the restitution defect in suckling pigs can be rescued by the direct application of homogenized mucosa from ischemia-injured small intestine from weaned pigs. Identifying reasons for this age-dependent defect in restitution and the components of the more mature pig mucosal tissues responsible for rescue will inform novel treatment interventions for neonates suffering with intestinal injury. Our lab has associated this age-dependent defect in barrier repair with an underdeveloped enteric glial cell (EGC) network, a postnatally developing component of the enteric nervous system known to regulate the intestinal barrier. We have found sub-epithelial EGC are reduced in neonates, neonatal epithelium in co-culture with EGC restitute more efficiently in vitro, and EGC inhibition ex vivo blocks restitution in juveniles recreating the neonatal phenotype. Further, as this EGC network is known to mature postnatally in response to the microbial colonization, we have found postnatal microbiota modulation with dietary prebiotic fiber supplementation exerts important effects on EGC network development and activity, and on EGC-epithelial pro-restitution crosstalk in vitro. Ongoing work to understand the roles of diet, microbiota, and the enteric nervous system on postnatal development of epithelial barrier repair can inform novel preventatives and interventions to improve intestinal health in vulnerable neonates.