Honey Added to Yogurt with Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 Supports Probiotic Enrichment but Does Not Reduce Intestinal Transit Time in Healthy Adults: A Randomized, Controlled, Crossover Trial.

BACKGROUND: Honey improves probiotic survival in vitro. However, if this effect translates to humans has not been investigated. OBJECTIVES: We aimed to determine effects of honey plus yogurt containing the probiotic Bifidobacterium animalis subsp. lactis DN-173 010/CNCM I-2494 (B. animalis) on intestinal transit time, probiotic enrichment, digestive health, mood, and cognition in adults. METHODS: Sixty-six healthy adults (34 female; 33.6 ± 9.8 y; 24.6 ± 3.0 kg/m2) in a crossover trial were randomly assigned to 2-wk yogurt conditions in a counterbalanced order with ≥4-wk washout: 1) Honey (HON): yogurt plus honey and 2) Negative Control (NC): heat-treated yogurt plus sugar. Of the participants, n = 62 completed the trial, and n = 37 (17 female; 32.0 ± 8.3 y; 25.0 ± 2.9 kg/m2) elected to enroll in a third condition (a nonrandomized study extension) after ≥4-wk washout with a reference Positive Control (PC): yogurt plus sugar. At baseline and end of each of the 3 conditions, intestinal transit time was measured with dye capsules; probiotic abundance with fecal sample 16S sequencing; digestive health with symptom/function records, Bristol stool consistency, Gastrointestinal Tolerability, and Gastrointestinal Quality of Life Index; mood with Positive and Negative Affect Schedule-Short Form, Depression Anxiety Stress Scales-42, Patient-Reported Outcomes Measurement Information System questionnaires, and an emotional image task; and cognition with a spatial reconstruction task. Data were analyzed using linear mixed-effects models (LMMs) with significance at P ≤ 0.05. Baseline and end data were included in the LMM, with fixed effects being treatment, time, treatment by time interaction, and baseline covariate, and the random effect being the participant. RESULTS: B. animalis was enriched in HON (d = 3.54; P = 0.0002) compared to controls with linear discriminant analysis effect size. Intestinal transit time, gastrointestinal health, mood, and cognition did not differ between conditions (LMM: Ps > 0.05). CONCLUSIONS: Yogurt + honey enriched B. animalis but did not reduce intestinal transit time or have other functional gastrointestinal, mood, or cognitive effects in adults. This trial was registered at www. CLINICALTRIALS: gov as NCT04187950 and NCT04901390.

SARS-CoV-2 Omicron BA.1 Variant Infection of Human Colon Epithelial Cells.

The Omicron variant of SARS-CoV-2, characterized by multiple subvariants including BA.1, XBB.1.5, EG.5, and JN.1, became the predominant strain in early 2022. Studies indicate that Omicron replicates less efficiently in lung tissue compared to the ancestral strain. However, the infectivity of Omicron in the gastrointestinal tract is not fully defined, despite the fact that 70% of COVID-19 patients experience digestive disease symptoms. Here, using primary human colonoids, we found that, regardless of individual variability, Omicron infects colon cells similarly or less effectively than the ancestral strain or the Delta variant. The variant induced limited type III interferon expression and showed no significant impact on epithelial integrity. Further experiments revealed inefficient cell-to-cell spread and spike protein cleavage in the Omicron spike protein, possibly contributing to its lower infectious particle levels. The findings highlight the variant-specific replication differences in human colonoids, providing insights into the enteric tropism of Omicron and its relevance to long COVID symptoms.

Honey Varietals Differentially Impact Bifidobacterium animalis ssp. lactis Survivability in Yogurt through Simulated In Vitro Digestion.

BACKGROUND: Bifidobacterium animalis ssp. lactis DN-173 010/CNCM I-2494 (B. animalis) is a probiotic strain commonly added to yogurt. Yogurt and honey are a popular culinary pairing. Honey improves bifidobacteria survival in vitro. However, probiotic survival in yogurt with honey during in vitro digestion has not been investigated. OBJECTIVES: The study aimed to evaluate the effects of different honey varietals and concentrations on B. animalis survivability in yogurt through in vitro digestion. METHODS: Yogurt with honey or control-treated samples underwent in vitro simulated oral, gastric, and intestinal digestion. B. animalis cells were enumerated on de Man Rogosa and Sharpe (MRS) medium followed by an overlay with a modified selective MRS medium; all underwent anaerobic incubation. B. animalis were enumerated predigestion and after oral, gastric, and intestinal digestion. There were 2 study phases: Phase 1 tested 4 honey varietals at 20% wt/wt per 170 g yogurt, and Phase 2 tested 7 dosages of clover honey (20, 14, 10, 9, 8, 6, and 4% wt/wt) per 170 g yogurt. RESULTS: Similar B. animalis counts were observed between all treatments after oral and gastric digestion (<1 Log colony forming units (CFU)/g probiotic reduction). Higher B. animalis survivability was observed in yogurt with clover honey after exposure to simulated intestinal fluids (∼3.5 Log CFU/g reduction; P < 0.05) compared to all control treatments (∼5.5 Log CFU/g reduction; P < 0.05). Yogurt with 10-20% wt/wt clover honey increased B. animalis survivability after simulated in vitro digestion (≤ ∼4.7 Log CFU/g survival; P < 0.05). CONCLUSIONS: Yogurt with added honey improves probiotic survivability during in vitro digestion. The effective dose of clover honey in yogurt was 10-20% wt/wt per serving (1-2 tablespoons per 170 g yogurt) for increased probiotic survivability during in vitro digestion.

Aggregative Behaviour of Spiny Butterfly Rays (Gymnura altavela, Linnaeus, 1758) in the Shallow Coastal Zones of Gran Canaria in the Eastern Central Atlantic.

The presence of spiny butterfly rays, Gymnura altavela, in waters less than 20 m deep off the Canary Islands shows marked seasonality, with relatively high abundances in the summer and autumn. Large aggregations of sometimes hundreds of individuals, primarily females, appear in specific shallow areas of the archipelago and seem to be associated with the seasonal variation in water temperature. This seasonal pattern of presence or absence in shallow areas suggests that spiny butterfly rays migrate into deeper waters or other unknown areas during the rest of the year. G. altavela shows sexual dimorphism; in our study, females were larger and more abundant than males, with a sex ratio of 1:18.9. The species' estimated asymptotic length, L∞, was 183.75 cm and thus close to the common length reported for the species (200 cm). The von Bertalanffy growth constant (k) oscillated between 0.210 and 0.310 year-1, as similarly described for the species in the Western North Atlantic off the U.S. coast. From June to November, the seawater temperature oscillated between 19 and 24 °C, and massive aggregations of females occurred at 22-24 °C and in a few specific sandy beaches on the islands. Spiny butterfly rays, mostly females, show a preference for aggregating in shallow waters during summertime, probably conditionate to mating or breeding behaviour.

First record of partial albinism in the critically endangered Angelshark (Squatina squatina) (Linnaeus, 1758).

We report the first case of partial albinism in the Critically Endangered angelshark, Squatina squatina. The encounter with this specimen took place while SCUBA diving on the beach of Tufia, located on the east coast of the island of Gran Canaria on 2 April 2021. This is also the first confirmed finding of an albino elasmobranch specimen in the Canary Island archipelago.

RBM47 regulates intestinal injury and tumorigenesis by modifying proliferation, oxidative response, and inflammatory pathways.

RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Rbm47-IKO mice exhibited increased proliferation and abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapted to radiation injury and were protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and developmental genes. Furthermore, Rbm47-IKO mice were protected against colitis-associated cancer. By contrast, aged Rbm47-IKO mice developed spontaneous polyposis, and Rbm47-IKO ApcMin/+ mice manifested an increased intestinal polyp burden. RBM47 mRNA was decreased in human colorectal cancer versus paired normal tissue, along with alternative splicing of tight junction protein 1 mRNA. Public databases revealed stage-specific reduction in RBM47 expression in colorectal cancer associated independently with decreased overall survival. These findings implicate RBM47 as a cell-intrinsic modifier of intestinal growth, inflammatory, and tumorigenic pathways.

Life History Parameters and Fishing Aspects of the Alien Nimble Spray Crab Percnon gibbesi in a Native Area of the Central-East Atlantic.

Percnon gibbesi is a native crab species characteristic of intertidal and subtidal zones of the Atlantic coast of the European Macaronesian archipelagos (Azores, Madeira, and Canary Islands), and probably also in the neighbouring rocky coasts of northwest Africa. P. gibbesi is considered an invasive alien species in almost all of the Mediterranean, with expanding populations from Spain to Turkey, including Libya; However, its biology and ecology are highly unknown, despite all its range of distribution. In the intertidal zones of Gran Canaria Island, this crab, in the intertidal zones of Gran Canaria Island, shows a carapace length range between 4.1 and 22.7 mm (4.1-22.7 in males and 5.7-22.3 in females), where females showed higher weights and lengths than males on average; However, males predominated in all samples, with a sex ratio of 1:0.57. The L∞ for this crab was estimated to be 27 ± 3 mm (23 ± 4 mm for females and 25 ± 4 mm for males). The growth coefficient (K) was 0.24 year-1, the total mortality (Z) was Z = 1.71 year-1, and the natural mortality (M) was 0.47 year-1. Although females grow faster than males, males are more abundant in the larger length classes. Although the presence of ovigerous females indicated that reproduction takes place twice a year, from March to April and from August to September, the number of cohorts detected by the modal progression analysis showed that reproduction takes place all year.

Inflammatory Bowel Disease Is Associated With an Increased Risk of Incident Acute Arterial Events: Analysis of the United Kingdom Biobank.

BACKGROUND & AIMS: Population-based studies have suggested an increased risk of acute arterial events (AAEs) in patients with inflammatory bowel disease (IBD). We aimed to assess the risk of incident AAEs and premature AAEs, adjusted for diet, physical activity, and inflammation biomarkers, in participants with IBD in the UK Biobank (UKB) METHODS: UKB participants with IBD and without prevalent AAEs at enrollment were matched to random non-IBD controls. A Cox regression model, adjusting for baseline cardiovascular and IBD risk factors, diet, physical activity, and high-sensitivity C-reactive protein, estimated adjusted hazard ratios (aHRs) for association between IBD and AAEs or premature AAEs (age, <55 years for men and <65 years for women). Predictors of AAEs within the IBD cohort were identified in a Cox model adjusting for disease severity (IBD-related hospitalizations or surgeries). RESULTS: Among 455,950 UKB participants, 5094 with IBD were matched to 20,376 non-IBD controls. After a median follow-up period of 12.4 years, participants with IBD had a higher incident rate of AAE (924.1 vs 730.9 per 100,000 person years; P < .001), risk of all AAEs (aHR, 1.19; 95% CI, 1.08-1.31; P < .001), and premature AAEs (aHR, 1.38; 95% CI, 1.11-1.72; P = .001). High-sensitivity C-reactive protein levels (highest quartile: aHR, 1.53; 95% CI, 1.15-2.03) and disease severity (aHR, 5.40; 95% CI, 4.03-7.22) were independent predictors of AAE in IBD. CONCLUSIONS: In a prospective cohort, there was an increased risk of incident AAEs and premature AAEs in IBD participants. Beyond traditional AAE risk factors, quantifiable indices of IBD disease activity and severity were independent predictors of AAEs.

Mutagénesis inducida en plantas de Solanum betaceum Cav. mediante el uso de dietil sulfato (DES) / Induced mutagenesis in Solanum betaceum Cav. plants by the use of diethyl sulphate (DES)

RESUMEN La materia prima del fitomejoramiento es la variabilidad genética, que se presenta baja, en especies en proceso de domesticación, que no han sido sometidas a selección, como en Solanum betaceum. Una de las tecnologías para incrementar la variabilidad genética es la inducción de mutagénesis. El objetivo del estudio fue evaluar, a través de marcadores RAMs, las variaciones moleculares presentes en plántulas de S. betaceum, provenientes de semillas sometidas a diferentes concentraciones del agente mutante dietil sulfato (DES). Los loci polimórficos oscilaron entre 87,5 y 100 % y el número de alelos efectivos (Ne), entre 1,0 y 1,99. Los loci más polimórficos se observaron en TG, AG, ACA y CGA, que mostraron una heterosis media insesgada entre 0,34 y 0,51, que permite establecer que estos marcadores sean útiles para obtener mayor discriminación entre mutantes en S. betaceum. Las distancias genéticas oscilaron entre 0,30 y 1,0. El 81,28 % de estos registros se dieron entre 0,60 y 0,90; esto revela bajo nivel de cambios, debido al DES. Estos pequeños cambios contribuyeron a enriquecer la variabilidad genética de la muestra tratada con DES. Los marcadores RAMs fueron útiles para detectar cambios entre plantas provenientes de semillas tratadas con DES y plantas normales. La variabilidad genética entre tratamientos con DES fueron más altos que tratamientos sin DES. Las similitudes genéticas fueron bajas entre plantas tratadas y no tratadas y fueron altas, entre no tratadas. Los cambios producidos por DES fueron de baja magnitud; sin embargo, produjeron cambios en los niveles de variabilidad genética.

ABSTRACT The raw material for plant breeding is genetic variability, which is low in species in the process of domestication that have not been subjected to selection, as is the case with Solanum betaceum. One of the technologies to increase genetic variability is mutagenesis induction. The objective was to evaluate, through RAMs markers, the molecular variations present in S. betaceum seedlings from seeds previously subjected to different concentrations of the mutant agent diethyl sulfate (DES). The polymorphic loci ranged from 87.5 to 100%, number of effective alleles (Ne) between 1.0 and 1.99. The most polymorphic loci were observed in TG, AG, ACA, and CGA, which showed a mean unbiased heterosis between 0.34 and 0.51 with an average of 0.44, which allows establishing that these markers are useful to obtain greater discrimination between mutants in S. betaceum. Genetic distances ranged from 0.30 to 1.0. The 81.28% of these records were between 0.60 and 0.90. This reveals a low level of changes due to DES. These small changes contribute to enriching the genetic variability of the DES-treated sample. The RAMs markers were useful for detecting changes between plants from DES treated seeds and normal plants. Genetic variability between DES treatments was higher than non-DES treatments. Genetic similarities were low between treated and untreated plants and were high among untreated plants. The changes produced by DES were of low magnitude, however, they produced changes in the levels of genetic variability.

The Prebiotic Potential of Inulin-Type Fructans: A Systematic Review.

Inulin-type fructans (ITF), including short-chain fructooligosaccharides (scFOS), oligofructose, and inulin, are commonly used fibers that are widely regarded as prebiotic for their ability to be selectively utilized by the intestinal microbiota to confer a health benefit. However, to our knowledge the literature thus far lacks a thorough discussion of the evidence from human clinical trials for the prebiotic effect of ITF, including beneficial effects on intestinal microbiota composition and intestinal and extraintestinal processes (e.g., glucose homeostasis, lipids, mineral absorption and bone health, appetite and satiety, inflammation and immune function, and body composition). Additionally, there has been a lack of discussion regarding aspects such as the effect of ITF chain length on its intestinal and extraintestinal effects. The overall objective of this systematic review was to summarize the prebiotic potential of ITF based on the results of human clinical trials in healthy adult populations. Evidence from studies included in the current review suggest that ITF have a prebiotic effect on the intestinal microbiota, promoting the abundances of Bifidobacterium, Lactobacillus, and Faecalibacterium prausnitzii. Beneficial health effects reported following ITF intake include improved intestinal barrier function, improved laxation, increased insulin sensitivity, decreased triglycerides and an improved lipid profile, increased absorption of calcium and magnesium, and increased satiety. Although there is some evidence for differing effects of ITF based on chain length, the lack of direct comparisons and detailed descriptions of physicochemical properties limits the ability to draw conclusions from human clinical studies. Future research should focus on elucidating the mechanisms by which the intestinal microbiota mediates or modifies the effects of ITF on human health and the contribution of individual factors such as age and metabolic health to the movement toward personalization of prebiotic applications.

Differences in the occurrence and abundance of batoids across an oceanic archipelago using complementary data sources: Implications for conservation.

Batoids, distributed from shallow to abyssal depths, are considerably vulnerable to anthropogenic threats. Data deficiencies on the distribution patterns of batoids, however, challenge their effective management and conservation. In this study, we took advantage of the particular geological and geomorphological configuration of the Canary Islands, across an east-to-west gradient in the eastern Atlantic Ocean, to assess whether patterns in the occurrence and abundance of batoids varied between groups of islands (western, central, and eastern). Data were collected from shallow (<40 m, via underwater visual counts and by a local community science program) and deep waters (60-700 m, via ROV deployments). Eleven species of batoids, assessed by the IUCN Red List of Threatened Species, were registered, including three "Critically Endangered" (Aetomylaeus bovinus, Dipturus batis, and Myliobatis aquila), three "Endangered" (Gymnura altavela, Mobula mobular, and Rostroraja alba), two "Vulnerable" (Dasyatis pastinaca and Raja maderenseis), and two "Data Deficient" (Taeniurops grabata and Torpedo marmorata). Also, a "Least Concern" species (Bathytoshia lata) was observed. Overall, batoids were ~1 to 2 orders of magnitude more abundant in the central and eastern islands, relative to the western islands. This pattern was consistent among the three sources of data and for both shallow and deep waters. This study, therefore, shows differences in the abundance of batoids across an oceanic archipelago, likely related to varying insular shelf area, availability of habitats, and proximity to the nearby continental (African) mass. Large variation in population abundances among islands suggests that "whole" archipelago management strategies are unlikely to provide adequate conservation. Instead, management plans should be adjusted individually per island and complemented with focused research to fill data gaps on the spatial use and movements of these iconic species.

Preliminary assessment of the impact of Covid-19 Pandemic in the small-scale and recreational fisheries of the Canary Islands.

Covid-19 pandemic has affected worldwide in many different ways. Fisheries around the world are not an exception due to the long-term isolation and the non-activities period suffered. To do an evaluation of its impact on the fishing sectors in the Canary Islands, 87 online and phone questionnaires were carried out between July and September 2020, conducting the interviews to artisanal fishermen, fishmongers, recreational charter boats fishermen and tackle shops along the archipelago. Both, the artisanal and recreational fishing sectors have been affected by this pandemic, but in an unequal manner. The drop of the demand of fresh fishing products in the islands markets due to the closure of hotels, restaurants and other services, and the highly significant decreasing in the number of tourists, provoked an estimated income loss for the artisanal fishermen about the 40% on average, but the majority of vessels continued their activities during the pandemic, with very limited effects on direct employment. However, the fishmonger's activity apparently was not affected and increased their monthly income in relation to the previous year. Likewise, the infeasibility of fishing charter companies due to the great reduction in the number of tourists contrasted with the significant increase in the number of recreational fishing licenses immediately after the confinement ended. Even though that fishing tackle shops increased sales by over 60% in relation to the similar period of the year before, only 4.4% of these shops declared not to have had economic losses.

Mesalamine Reduces Intestinal ACE2 Expression Without Modifying SARS-CoV-2 Infection or Disease Severity in Mice.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) is an ongoing public health crisis that has sickened or precipitated death in millions. The etiologic agent of COVID-19, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infects the intestinal epithelium, and can induce GI symptoms similar to the human inflammatory bowel diseases (IBD). An international surveillance epidemiology study (SECURE-IBD) reported that the standardized mortality ratio trends higher in IBD patients (1.5-1.8) and that mesalamine/sulfasalazine therapy correlates with poor outcome. The goal of our study was to experimentally address the relationship between mesalamine and SARS-CoV-2 entry, replication, and/or pathogenesis. METHODS: Viral infection was performed with a chimeric vesicular stomatitis virus expressing SARS-CoV-2 spike protein and EGFP (VSV-SARS-CoV-2) and SARS-CoV-2 virus derived from an infectious cDNA clone of 2019n-CoV/USA_WA1/2020. Primary human ileal spheroids derived from healthy donors were grown as 3D spheroids or on 2D transwells. We assessed the effect of 10 mM mesalamine (Millipore Sigma) on viral RNA levels, as well as the expression of the SARS-CoV-2 receptor angiotensin II-converting enzyme 2 (ACE2), Transmembrane Serine Protease 2 (TMPRSS2), TMPRSS4, Cathepsin B (CTSB) and CTSL by qRT-PCR. 8-12 week old K18-ACE2 were treated orally with PBS or mesalamine at 200 mg/kg daily. Mice were inoculated intranasally with 1Ã-10 3 FFU of SARS-CoV-2. Mice were weighed daily and viral titers were determined 7 days post infection (dpi) by qRT-PCR. For the intestinal viral entry model, VSV-SARS-CoV-2 was injected into a ligated intestinal loop of anesthetized K18-ACE2 mice and tissues were harvested 6 hours post-infection. RESULTS: We found no change in viral RNA levels in human intestinal epithelial cells in response to mesalamine. Expression of ACE2 was reduced following mesalamine treatment in enteroids, while CTSL expression was increased. Mice receiving mesalamine lost weight at similar rates compared to mice receiving vehicle control. Mesalamine treatment did not change viral load in the lung, heart, or intestinal tissues harvested at 7 dpi. Pretreatment with mesalamine did not modulate intestinal entry of the chimeric VSV-SARS-CoV-2 in K18-ACE2 mice. CONCLUSIONS: Mesalamine did not alter viral entry, replication, or pathogenesis in vitro or in mouse models. Mesalamine treatment reduced expression of the viral receptor ACE2 while concurrently increasing CTSL expression in human ileum organoids.

Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice.

Goblet cells (GCs) are specialized cells of the intestinal epithelium contributing critically to mucosal homeostasis. One of the functions of GCs is to produce and secrete MUC2, the mucin that forms the scaffold of the intestinal mucus layer coating the epithelium and separates the luminal pathogens and commensal microbiota from the host tissues. Although a variety of ion channels and transporters are thought to impact on MUC2 secretion, the specific cellular mechanisms that regulate GC function remain incompletely understood. Previously, we demonstrated that leucine-rich repeat-containing protein 26 (LRRC26), a known regulatory subunit of the Ca2+-and voltage-activated K+ channel (BK channel), localizes specifically to secretory cells within the intestinal tract. Here, utilizing a mouse model in which MUC2 is fluorescently tagged, thereby allowing visualization of single GCs in intact colonic crypts, we show that murine colonic GCs have functional LRRC26-associated BK channels. In the absence of LRRC26, BK channels are present in GCs, but are not activated at physiological conditions. In contrast, all tested MUC2- cells completely lacked BK channels. Moreover, LRRC26-associated BK channels underlie the BK channel contribution to the resting transepithelial current across mouse distal colonic mucosa. Genetic ablation of either LRRC26 or BK pore-forming α-subunit in mice results in a dramatically enhanced susceptibility to colitis induced by dextran sodium sulfate. These results demonstrate that normal potassium flux through LRRC26-associated BK channels in GCs has protective effects against colitis in mice.

CEACAMs serve as toxin-stimulated receptors for enterotoxigenic Escherichia coli.

The enterotoxigenic Escherichia coli (ETEC) are among the most common causes of diarrheal illness and death due to diarrhea among young children in low-/middle-income countries (LMICs). ETEC have also been associated with important sequelae including malnutrition and stunting, placing children at further risk of death from diarrhea and other infections. Our understanding of the molecular pathogenesis of acute diarrheal disease as well as the sequelae linked to ETEC are still evolving. It has long been known that ETEC heat-labile toxin (LT) activates production of cAMP in the cell, signaling the modulation of cellular ion channels that results in a net efflux of salt and water into the intestinal lumen, culminating in watery diarrhea. However, as LT also promotes ETEC adhesion to intestinal epithelial cells, we postulated that increases in cAMP, a critical cellular "second messenger," may be linked to changes in cellular architecture that favor pathogen-host interactions. Indeed, here we show that ETEC use LT to up-regulate carcinoembryonic antigenrelated cell adhesion molecules (CEACAMs) on the surface of small intestinal epithelia, where they serve as critical bacterial receptors. Moreover, we show that bacteria are specifically recruited to areas of CEACAM expression, in particular CEACAM6, and that deletion of this CEACAM abrogates both bacterial adhesion and toxin delivery. Collectively, these results provide a paradigm for the molecular pathogenesis of ETEC in which the bacteria use toxin to drive up-regulation of cellular targets that enhances subsequent pathogen-host interactions.

Stem cell and niche regulation in human short bowel syndrome.

Loss of functional small bowel surface area following surgical resection for disorders such as Crohn's disease, intestinal ischemic injury, radiation enteritis, and in children, necrotizing enterocolitis, atresia, and gastroschisis, may result in short bowel syndrome, with attendant high morbidity, mortality, and health care costs in the United States. Following resection, the remaining small bowel epithelium mounts an adaptive response, resulting in increased crypt cell proliferation, increased villus height, increased crypt depth, and enhanced nutrient and electrolyte absorption. Although these morphologic and functional changes are well described in animal models, the adaptive response in humans is less well understood. Clinically the response is unpredictable and often inadequate. Here we address the hypotheses that human intestinal stem cell populations are expanded and that the stem cell niche is regulated following massive gut resection in short bowel syndrome (SBS). We use intestinal enteroid cultures from patients with SBS to show that the magnitude and phenotype of the adaptive stem cell response are both regulated by stromal niche cells, including intestinal subepithelial myofibroblasts, which are activated by intestinal resection to enhance epithelial stem and proliferative cell responses. Our data suggest that myofibroblast regulation of bone morphogenetic protein signaling pathways plays a role in the gut adaptive response after resection.