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The digestion of starch-based foods in the intestinal tract is important for human health. Modeling the details enhances fundamental understanding and glycemic prediction accuracy. It is, however, a challenge to take granular properties into account. A multiscale digestion model has been proposed to characterize mass transfer and hydrolysis reaction at both the intestine and particle scales, seamlessly integrating inter-scale mass exchange. A specific grid scheme was formulated for the shrinkage and transport of the particle computational domain. By incorporating additional glycemic-related processes, e.g., intestinal absorption, a dietary property-based glycemic prediction system has been developed. Its effectiveness was validated based on a human tolerance experiment of cooked rice particles. The model-based investigation comprehensively reveals the impact of initial size on digestion behavior, specifically in terms of enzyme distribution and particle evolution. This work also demonstrates the significance of modeling both particle-scale diffusion and intestine-scale transport, a combination not previously explored. The results indicate that ignoring the former mechanism leads to an overestimation of the glycemic peak by at least 50.8%, while ignoring the latter results in an underestimation of 16.3%.

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Lentinula edodes (Shiitake) is an important edible mushroom and polysaccharides are its major constituents with proven health benefits. The study was to investigate the gut bacterial fermentation and subsequent effects on gut barrier function of a glucan-rich polysaccharide, LePS40 precipitated from the mushroom water extract with 40 % (v/v) ethanol. LePS40 consisted of a ß-(1→3)-glucan main chain with substitution in the C-6 position with side chains mainly composed of (1 → 6)-linked ß-Glcp residues, (1 → 6)-linked α-Galp residues and terminal residues of ß-Glcp. LePS40 was found highly resistant to digestive enzymes and gastric acid in simulated human gastrointestinal tract, but highly fermentable during in vitro human fecal fermentation. The fecal fermentation degradation of LePS40 appeared to selectively break the glucoside linkage in view of the dramatic decrease in the glucose molar ratio (12.68 to 1.07). Compared with the prebiotic reference FOS, LePS40 led to much higher levels of butyric, and propionic acid and a lower level of acetic acid. Moreover, LePS40 enhanced the abundance of some beneficial bacterial populations, but decreased the bacteria possibly linked with fatty-liver disease and colorectal cancer. Furthermore, the fecal fermentation products of LePS40 showed a potential protective effect on intestinal barrier function against inflammatory damage in Caco-2/Raw264.7 co-culture model. These findings suggest the potential of LePS40 for improvement of gut health through modulation of gut microbiota.

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Introduction: 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a promising emulsifier for bioactive delivery systems, but its industrial applications are limited by the lack of cost-effective and scalable synthetic routes. The purpose of this study was to economically produce high-purity DMPC by replacing commonly used column chromatography methods and to evaluate the emulsifying performance. Methods: DMPC was synthesized from sn-glycero-3-phosphocholine using Steglich esterification followed by sequential recrystallization from ethyl acetate and acetone. The structure of DMPC was identified and its purity was confirmed using various spectroscopy and chromatography techniques. The emulsifying performance was evaluated by examining the effects of storage on the properties of o/w emulsions prepared using soybean oil with (i) soy PC, (ii) soy PC + DMPC (1:1, w/w), and (iii) DMPC as emulsifiers. Results: The chemical impurities formed during the synthesis of DMPC was removed, and its final purity was 96%, and the melt transition temperature was 37.6°C. No visible difference between the three emulsions (soy PC, soy PC+DMPC, and DMPC) was observed during two-week storage, and the DMPC-based emulsion was more stable than soy PC emulsion, showing smaller particle size distribution during 6 months. Discussion: The highly pure DMPC was synthesized by an economical method, and DMPC-based emulsions demonstrated physicochemical stable, highlighting its potential for food and pharmaceutical industry-related applications. Our findings suggest that DMPC holds promise as an emulsifier with broad applications in the food industry.

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The use of animal experiments can be minimized with computational models capable of reflecting the simulated environments. One such environment is intestinal fluid and the colloids formed in it. In this study we used molecular dynamics simulations to investigate solubilization patterns for three model drugs (carvedilol, felodipine and probucol) in dog intestinal fluid, a lipid-based formulation, and a mixture of both. We observed morphological transformations that lipids undergo due to the digestion process in the intestinal environment. Further, we evaluated the effect of bile salt concentration and observed the importance of interindividual variability. We applied two methods of estimating solubility enhancement based on the simulated data, of which one was in good qualitative agreement with the experimentally observed solubility enhancement. In addition to the computational simulations, we also measured solubility in i) aspirated dog intestinal fluid samples and ii) simulated canine intestinal fluid in the fasted state, and found there was no statistical difference between the two. Hence, a simplified dissolution medium suitable for in vitro studies provided physiologically relevant data for the systems explored. The computational protocol used in this study, coupled with in vitro studies using simulated intestinal fluids, can serve as a useful prescreening tool in the process of drug delivery strategies development.

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The effects of different thermal sterilization conditions on the quality and digestibility of ready-to-eat (RTE) shrimp were investigated. Compared with the high-temperature (121 °C) and short-time (6 min and 8 min) sterilization, the low-temperature (110 and 115 °C) and long-time (>20 min) sterilization significantly promoted the Maillard and browning reactions and changed the color of the RTE-shrimp. The high sterilization temperature promoted shrimp protein oxidation, resulting in increased carbonyl group, disulfide bond, and free radical content, while the free sulfhydryl group content decreased. This oxidation and tissue destruction at high temperature led to reduced texture properties and altered water distribution within the shrimp's muscles. However, sterilized shrimp exhibited superior digestive properties in an in vitro simulated digestion experiment. High-temperature and short-time sterilization is more effective in mitigating the quality deterioration of RTE-shrimp compared to low-temperature and long-time sterilization.

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The importance of gastric digestion in starch-based emulsion is often overshadowed compared to intestinal digestion, despite acknowledging the activity of salivary α-amylase in the stomach. This study aimed to address this gap by investigating the digestion of starch-based emulsions through orogastrointestinal digestion experiments. Our observations revealed the crucial role of salivary α-amylase, which hydrolyzed ∼8 %, ∼56 %, and âˆ¼ 28 % of starch in emulsions stabilized by octenylsuccinylated maize starch (OMS-E), gelatinized OMS (GOMS-E), and retrograded OMS (ROMS-E), respectively, during the gastric phase. Consequently, ∼23 % of the oil in GOMS-E underwent lipolysis during this phase, whereas ∼13 and âˆ¼ 6 % of the oil was lipolyzed in OMS-E and ROMS-E, respectively. These phenomena significantly influenced their small intestinal digestion and the bioaccessibility of encapsulated curcumin. Notably, GOMS-E exhibited ∼28 % lower curcumin bioaccessibility than that of curcumin encapsulated in OMS-E or ROMS-E. This difference was attributed to premature gastric digestion and subsequent encapsulant release in the case of GOMS-E. This understanding can be utilized to manipulate the delivery and digestion of starch-based emulsions. Importantly, our findings highlight the necessity of considering gastric amylolysis and lipolysis when investigating the gastrointestinal fate of starch-based emulsions.

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The objective of this study was to characterize ruminal degradation, intestinal digestion and total true nutrient supply to dairy cows from canola feedstock (canola seeds) and coproducts (meal and pellets) from bio-oil processing which were impacted by source origin. The feedstocks and coproducts (mash, pellet) were randomly collected from five different bio-oil processing plants with five different batches of samples in each bio-processing plant in Canada (CA) and China (CH). In situ rumen degradation kinetics were determined using four fistulated Holstein cows with incubation times at 0, 2, 4, 8, 12, 24 and 48 h. Intestinal digestions were determined using the three-step in vitro method with preincubation at 12 h. The DVE/OEB and National Research Council systems were applied to evaluate the truly absorbable nutrient supply to dairy cows and feed milk values (FMVs). The results showed that in situ undegradable fractions (U) (p = 0.025) were higher in CA meals, and potentially degradable fraction of D was higher (p = 0.016) in CH meals. CH meals had higher total digestible dry matter (TDDM, p = 0.018) and intestinal digestibility of protein (dIDP, p = 0.016). Canola meals from CA had lower MREE (microbial protein synthesized in the rumen based on available rumen degradable protein; p = 0.011) and DVME (rumen synthesized microbial protein digested in the small intestine; p = 0.011) and had higher ECP (endogenous protein in the small intestine, p = 0.001) and absorbed endogenous crude protein (truly absorbed ECP in the small intestine) than CH (p = 0.001). The FMV evaluated based on the metabolic protein and net energy showed no differences between CA and CH in both coproducts and feedstocks.

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The aim of the present work was to evaluate and compare in vitro the antioxidant activity of raw, cooked and cooked-digested pork, beef and chicken burgers. The cooking process influenced the antioxidant capacity of the meat by decreasing the values of ABTS, FRAP and the content of free thiols. Conversely, a positive effect was observed after in vitro gastrointestinal digestion which increased the biological activity of the meat, characterised by greater antioxidant activity. The type of meat influenced the chemical composition and biological capacity of the burgers. In fact, both before and after the cooking process, beef burgers showed higher thiol content and, consequently, a higher oxidative stability of proteins than chicken and pork burgers. In vitro gastrointestinal digestion also improved the nutraceutical quality of beef burgers, which showed higher ABTS values and thiol content than pork burgers, which showed higher FRAP values. This work aims to support the potential of meat constituents as a natural antioxidant component that is essential to counteract the oxidative stress responsible for imbalances in the human organism and several cardiovascular diseases.

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Chickpeas are an agriculturally-important legume that are an excellent source of protein, fiber, and minerals. Developing chickpea-based snacks could provide consumers with snack products rich in protein and other nutrients. In this study, chickpea puree (high moisture content) and cracker (low moisture content) were each produced with large (7 mm sieve; coarse) or small (2 mm sieve; fine) particle size to investigate the impact of initial particle size and moisture content on particle breakdown, starch hydrolysis, and protein hydrolysis during in vitro digestion. All treatments underwent static in vitro oral digestion, dynamic gastric digestion in the Human Gastric Simulator (HGS), and static in vitro small intestinal digestion. The emptying rate from the HGS was significantly (p < 0.05) higher for fine puree compared to the other treatments, due to higher saturation ratio and smaller initial particle size. The reducing sugars and free amino groups released (representing starch and protein hydrolysis, respectively) from fine puree were higher than coarse puree, and fine cracker was higher than coarse cracker due to the influence of initial particle size. For example, after 360 min total in vitro digestion, the starch hydrolysis of the fine cracker (48.1 ± 3.2%) was significantly higher than (p < 0.05) the coarse cracker (36.3 ± 5.8%). Overall, crackers had higher protein and starch hydrolysis compared to puree in the liquid phase during digestion. The study showed that both the smaller initial particle size and drying significantly (p < 0.05) increased the particle size reduction during gastric digestion and starch and protein digestibility in chickpea-based snacks.

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In this study, we developed a novel delivery system using carboxymethyl konjac glucomannan-chitosan (CMKGM-CS) nanogels stabilized single and double emulsion incorporated into alginate hydrogel as microcapsule matrix for intestinal-targeted delivery of probiotics. Through in vitro experiments, it was demonstrated that alginate hydrogel provided favorable biocompatible growth conditions for the proliferation of Lactobacillus reuteri (LR). The alginate hydrogel containing single (ASE) or double emulsions (ACG) enhanced the resistance of LR to various adverse environments. Simulated gastrointestinal digestion experiments revealed that the survivability of LR in free, CON, ASE and ACG group decreased by 6.45 log CFU/g, 4.21 log CFU/g, 1.26 log CFU/g and 0.65 log CFU/g, respectively. In vivo studies conducted in mice showed that ACG maintained its integrity during passage through the stomach and released the probiotics in the targeted intestinal area, whereas the pure alginate hydrogels (CON) were prematurely released in the gastrointestinal tract. Moreover, the viable counts of ACG in different intestinal segments (jejunum, ileum, cecum, and colon) were increased by 1.11, 1.42, 1.68, and 1.89 log CFU/g, respectively, after 72 h of oral administration compared to the CON group. This research contributed valuable insights into the development of an effective microbial delivery system with potential applications in the biopharmaceutical and food industries.

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Three Streptococcus thermophilus strains, namely RBC6, RBC20, and RBN16, were proven to release bioactive peptides during whey protein concentrate (WPC) fermentation, resulting in WPC hydrolysates with biological activities. However, these bioactive peptides can break down during gastro-intestinal digestion (GID), hindering the health-promoting effect of fermented WPC hydrolysates in vivo. In this work, the effect of simulated GID on three WPC hydrolysates fermented with S. thermophilus strains, as well as on unfermented WPC was studied in terms of protein hydrolysis, biological activities, and peptidomics profiles, respectively. In general, WPC fermentation enhanced protein hydrolysis compared to unfermented WPC. After in vitro GID, WPC fermented with S. thermophilus RBC20 showed the highest antioxidant activity, whereas WPC fermented with strain RBC06 displayed the highest angiotensin-converting enzyme (ACE)- and dipeptidyl peptidase IV (DPP-IV)-inhibitory activities. Peptidomics analysis revealed that all digested WPC samples were highly similar to each other in peptide profiles, and 85% of the 46 identified bioactive peptides were shared among fermented and unfermented samples. However, semi-quantitative analysis linked the observed differences in biological activities among the samples to differences in the amount of bioactive peptides. The anti-hypertensive peptides VPP and IPP, as well as the DPP-IV-inhibitory peptide APFPE, were quantified. In conclusion, WPC fermentation with S. thermophilus positively impacted protein hydrolysis and bioactive peptide release during GID.

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Opuntia cactus fruit (prickly pear flesh and agricultural residues such as peels and stalks) is an important source of bioactive compounds, including betalains and phenolic compounds. In this work, two double emulsion W1/O/W2 formulations (A and B) were designed to encapsulate green extracts rich in betalains and phenolic compounds obtained from Opuntia stricta var. dillenii (OPD) fruits with the aim of improving their stability and protecting them during the in vitro gastrointestinal digestion process. In addition, the characterization of the double emulsions was studied by microscopy and the evaluation of their physical and physico-chemical parameters. Formulation A, based on Tween 20, showed smaller droplets (1.75 µm) and a higher physical stability than Formulation B, which was achieved with sodium caseinate (29.03 µm). Regarding the encapsulation efficiency of the individual bioactives, betalains showed the highest values (73.7 ± 6.7 to 96.9 ± 3.3%), followed by flavonoids (68.2 ± 5.9 to 95.9 ± 7.7%) and piscidic acid (71 ± 1.3 to 70.2 ± 5.7%) depending on the formulation and the bioactive compound. In vitro digestive stability and bioaccessibility of the individual bioactives increased when extracts were encapsulated for both formulations (67.1 to 253.1%) in comparison with the non-encapsulated ones (30.1 to 64.3%), except for neobetanin. Both formulations could be considered as appropriate microcarrier systems for green OPD extracts, especially formulation A. Further studies need to be conducted about the incorporation of these formulations to develop healthier foods.

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BACKGROUND: How starch-based food structure can affect the rate and extent of digestion in the small intestine and resulting glycemic response is not properly understood. One possible explanation is that food structure influences gastric digestion, which subsequently determines digestion kinetics in the small intestine and glucose absorption. However, this possibility has not been investigated in detail. OBJECTIVES: Using growing pigs as a digestion model for adult humans, this study aimed to investigate how physical structure of starch-rich foods affects small intestinal digestion and glycemic response. METHODS: Male growing pigs (21.7 ± 1.8 kg, Large White × Landrace) were fed one of the 6 cooked diets (250-g starch equivalent) with varying initial structures (rice grain, semolina porridge, wheat or rice couscous, or wheat or rice noodle). The glycemic response, small intestinal content particle size and hydrolyzed starch content, ileal starch digestibility, and portal vein plasma glucose were measured. Glycemic response was measured as plasma glucose concentration collected from an in-dwelling jugular vein catheter for up to 390 min postprandial. Portal vein blood samples and small intestinal content were measured after sedation and euthanasia of the pigs at 30, 60, 120, or 240 min postprandial. Data were analyzed with a mixed-model ANOVA. RESULTS: The plasma glucose Δmaxoverall and iAUCoverall for couscous and porridge diets (smaller-sized diets) were higher than that of intact grain and noodle diets (larger-sized diets): 29.0 ± 3.2 compared with 21.7 ± 2.6 mg/dL and 5659 ± 727 compared with 2704 ± 521 mg/dL⋅min, for the smaller-sized and larger-sized diets, respectively (P < 0.05). Ileal starch digestibility was not significantly different between the diets (P ≥ 0.05). The iAUCoverall was inversely related to the starch gastric emptying half-time of the diets (r = -0.90, P = 0.015). CONCLUSIONS: Starch-based food structure affected the glycemic response and starch digestion kinetics in the small intestine of growing pigs.

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In this study, a novel peptide, AEYLCEAC with high angiotensin-I-converting enzyme inhibitory (ACEI) activity was screened from oyster (Crassostrea gigas) hydrolysates, which was obtained from simulated gastro-intestinal digestion. Candidate peptides were confirmed to have a higher binding to angiotensin-I-converting enzyme (ACE) than the positive drug phosphoinic tripeptide calculated by Discovery Studio, and AEYLCEAC showed the highest ACE inhibition rate in vitro with a IC 50 of 4.287 mM. Lineweaver-Burk plots confirmed that the peptidic inhibitory type of ACE is competitive. The molecular docking showed that ACEI activity of the AEYLCEAC was mainly due to the hydrogen bonding interactions with the active pockets (S1 and S2) of ACE. In vivo, AEYLCEAC effectively reduced diastolic blood pressure (DBP) and Systolic blood pressure (SBP) in hypertensive rats. These results indicate that AEYLCEAC might act as a helpful ingredient in functional foods or pharmaceuticals for the prevention and treatment of hypertension.

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This study investigated the effects of diet with different amylose−amylopectin ratios (AAR) on the growth performance, intestinal morphology, digestive enzyme activities and mRNA expression of nutrients transporters in piglets with short-term lipopolysaccharide (LPS) intraperitoneal injections. Sixty 21 days-old piglets (Landrace × Yorkshire; 6.504 ± 0.079) were randomly assigned based on their body weight (BW) and litters of origins to five groups with experimental diets with an AAR of 0.00, 0.20, 0.40, 0.60, or 0.80 (namely, the 0.00, 0.20, 0.40, and 0.80 groups), respectively. Each treatment included 12 piglets (one piglet per pen). This experiment lasted for 28 days. On the 28th day, six piglets in each treatment were randomly selected for an LPS intraperitoneal injection (100 µg/kg BW), and other piglets were injected with normal saline. Twelve hours after LPS injection, all piglets were sacrificed to collect small intestinal mucosa for analysis. Although different AAR did not influence the final BW in piglets, the piglets in the 0.40 group represented the poorest feed-to-gain ratio (F/G) in the first, second and fourth week (p < 0.05) and the lowest average daily gain (ADG) in the fourth week (p < 0.05) compared with other groups. In terms of the small intestinal morphology, piglets in the 0.20 and 0.60 groups showed better ileal villous width (p < 0.05). Piglets in the 0.60 group presented greater activities of jejunal maltase, sucrase and alkaline phosphatase (p < 0.05) than those of 0.20 and 0.40. However, a low amylose diet increased the mRNA expression of jejunal glucose and amino acid transporters (p < 0.05). In addition, compared to saline injection, the LPS challenge significantly lessened jejunal digestive enzyme activities (p < 0.01) and, ileal villous width and downregulated the gene expression of glucose and amino acid transporters (p < 0.05) in piglets. Interestingly, certain diet -LPS interactions on duodenal VH/CD, jejunal maltase activity (p < 0.05) and the expression of glucose transporters (p < 0.05) were observed. Taken together, in terms of small intestinal digestion and absorption capacity, these results demonstrated that a diet with an AAR of 0.60 diets could improve the intestinal digestive and absorptive capability by affecting small intestinal morphology, digestive enzymes, and nutrients absorptions in piglets. In addition, the diets containing an AAR of 0.40−0.60 were more likely to resist the damage of LPS stress to intestinal morphology and nutrient absorption.

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In this paper, effect of emulsion stability on gastroduodenal emptying/secretion was reviewed and differentiated. Moreover, novel perspectives on physiology of gastric lumen, duodenum, and gall bladder were achieved using mathematical models, being useful for designing artificial digestive systems. In this regard, numerical data for dynamic gastric emptying/secretion were offered for gastric-stable and gastric-unstable emulsion intakes. It was shown that alterations in human gastric and duodenal volume follow, respectively, linear and sinusoidal curves, with high correlation coefficients (r2 > 0.93). For both emulsions, about 30-40 mL ingesta discharged rapidly from stomach upon ingestion; However, further gastric emptying was regulated for the rest of digestion period, so that 0.1 mL/min oil was passing through duodenum. Intragastric evacuation of both emulsions started with a lag phase during which stomach stored secretions incrementally by slow gastric discharge. Lag phase ended with fat layering, when emptying considerably enhanced. This reduction was gradual for stable emulsion while unstable emulsion experienced a rapid emptying before slow declining trend. Along with initial gastric emptying, 87% of gallbladder content discharged into duodenum, prolonged up to the gradual reduction phase of stomach. Supplementary investigations are needed to quantify gastroduodenal secretions, particularly pepsin and pancreas in response to emulsion ingesta.

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Despite human recombinant H2 relaxin or serelaxin holding promise as a cardiovascular drug, its actual efficacy in chronic treatment of heart failure patients was hampered by the need to be administered by multiple daily IV injections for a long time, with obvious drawbacks in terms of patients' compliance. This in vitro study aimed at exploring the molecular background for a possible administration of the peptide hormone relaxin by the oral route. Serelaxin and purified porcine relaxin (pRLX) were subjected to simulated intestinal fluid (SIF) enzymatic digestion in vitro to mimic the behavior of gastroprotective formulations. The digestion time course was studied by HPLC, and the relative bio-potency of the intact molecules and their proteolytic fragments was assessed by second messenger (cAMP) response in RXFP1 relaxin receptor-bearing THP-1 human monocytic cells. Both intact proteins (100 ng/mL) induced a significant cAMP rise in THP-1 cells. Conversely, SIF-treated serelaxin showed a brisk (30 s) bioactivity decay, dropping down to the levels of the unstimulated controls at 120 s, whereas SIF-treated pRLX retained significant bioactivity for up to 120 s. After that, it progressively declined to the levels of the unstimulated controls. HPLC analysis indicates that this bioactivity could be ascribed to a minor component of the pRLX sample more resistant to proteolysis. When identified and better characterized, this peptide could be exploited for the development of synthetic relaxin agonists suitable for oral formulations.

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The in-vitro gastrointestinal digestion behaviour of an oil-in-water emulsion with an interface consisting of nano-sized droplets coated with caseinate particles, referred to as a droplet-stabilised emulsion (DSE), was explored using the human gastric simulator and pH-stat models. A caseinate-particle-stabilised emulsion (PSE) was used as a control, with a similar droplet size distribution and the same composition as the DSE. The nanodroplet-stabilised interface of the DSE was preserved during the first 180 min of gastric digestion. During 240 min, the droplet sizes of the DSE and the PSE increased from 22.71 ± 1.14 to 63.34 ± 6.57 µm and from 17.98 ± 1.16 to 85.11 ± 9.35 µm respectively. The small droplet size of the DSE that was released from the gastric phase contributed to slightly higher total free fatty acid (FFA) release (56.18 ± 3.55%) than that from the PSE (49.4 ± 2.67%). The FFA release rate of the DSE (1.21 % min-1) was greater than that of the PSE (1.06 % min-1) during the first 30 min of small intestinal digestion; similar FFA release rates (0.5 µmol s-1 m-2 × 10-4) were obtained for both emulsions beyond 30 min of digestion. This study provides new information on lipid digestion using a novel interfacial layer that was stabilised with nanodroplets.

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Arthrospira platensis (Spirulina) has been credited with multiple beneficial effects, many of which are attributed to bioactive peptides produced during the gastrointestinal digestion of this micro-alga. Many Spirulina-based nutraceuticals have been produced, and numerous functional foods enriched with Spirulina are available on the market. These are subjected to checks aimed at verifying the amount of algae actually present, but few studies relating to the bioavailability of the bioactive compounds in these products have been carried out. However, such investigations could be very important to elucidate the possible critical effects exerted by food matrices on protein digestion and bioactive peptide production. Here, in order to assess the suitability of Spirulina-enriched foods as a source of potentially bioactive peptides, a simulated digestion protocol was used in combination with mass spectrometry quantitative analysis to analyze functionalized pasta and sorbets. In the case of the pasta enriched with Spirulina, the production of peptides was quite similar to that of the Spirulina powder. On the other hand, the type of fruit present in the food matrix influenced the digestion of Spirulina inside the sorbets. In particular, the high concentration of protease inhibitors in kiwifruit drastically reduced the production of peptides from Spirulina in kiwi sorbet.

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BACKGROUND: Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acute malnutrition (SAM), to define key features of these malnutrition-related enteropathies. METHODS: RNA was extracted and sequenced from biopsies of children with SAM in hospital (n=27), children with non-responsive stunting in the community (n=30), and adults living in the same community (n=37) using an identical sequencing and analysis pipeline. Two biopsies each were profiled and differentially expressed genes (DEGs) were computed from the comparisons of the three groups. DEG lists from these comparisons were then subjected to analysis with CompBio software to assemble a holistic view of the biological landscape and IPA software to interrogate canonical pathways. FINDINGS: Dysregulation was identified in goblet cell/mucin production and xenobiotic metabolism/detoxification for both cohorts of children, versus adults. Within the SAM cohort, substantially greater induction of immune response and barrier function, including NADPH oxidases was noted, concordant with broadly reduced expression of genes associated with the brush border and intestinal structure/transport/absorption. Interestingly, down regulation of genes associated with the hypothalamic-pituitary-adrenal axis was selectively observed within the cohort of children with stunting. INTERPRETATION: Gene expression profiles in environmental enteropathy and severe acute malnutrition have similarities, but SAM has several distinct transcriptional features. The intestinal capacity to metabolise drugs and toxins in malnourished children requires further study. FUNDING: Bill & Melinda Gates Foundation (OPP1066118).

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