Search Results (12)

Background: Sarcina ventriculi is a bacterium predominantly reported in the stomach and associated with emphysematous gastritis, delayed gastric emptying, gastroparesis, or gastric outlet obstruction. Its prevalence is increasing among patients with a history of organ transplants, immunosuppression, and graft-versus-host disease (GVHD). This bacterium can be detected on histology with characteristic tetrad packet morphology; however, confirmation requires PCR and molecular studies. The role of Sarcina ventriculi in human diseases is not fully understood and has unclear clinical significance. While certain studies point to a possible pathogenic role, others regard its detection as incidental with no clear clinical consequence. Case presentation: Herein, we report a case of a 39-year-old male patient with primary refractory cHL, stage IVb, who underwent an autologous bone marrow transplant (BMT) and an allogeneic stem cell infusion. His post-transplant course was complicated by chronic kidney disease (CKD), malnutrition, depression, myopathy, skin, and colon GVHD. He eventually developed sepsis, was admitted to the ICU and developed multiorgan failure and passed away. The patient developed diarrhea, and the gastrointestinal specialist was consulted and revealed ulcerated ileitis and colitis. Biopsies were taken to evaluate for CMV infection and GVHD. The terminal ileum biopsy mainly revealed ulceration with granulation tissue formation and abundant microorganisms arranged in distinctive tetrads, characteristic of Sarcina ventriculi. The colonic biopsies were consistent with GVHD grade II. Conclusions: The significance of Sarcina microorganisms and their mechanisms of injury remain poorly understood. The identification of Sarcina ventriculi in the terminal ileum, which is an unusual and previously unreported finding, adds a new perspective to our understanding of its pathogenic potential and anatomical distribution. While the patient’s clinical decline was influenced by multiple factors, including GVHD, recurrent sepsis, and multiorgan failure, the role of Sarcina ventriculi as a potential exacerbating factor remains unclear. Full article

Background: Gastrointestinal mucosal damage due to human immunodeficiency virus (HIV) infection leads to microbial translocation and immune activation, contributing to the development of non-infectious comorbidities (NICM) in people living with HIV (PLWH). Additionally, persistent proviral HIV-1 in the gut-associated lymphatic tissue (GALT) can trigger immunological changes in the epithelial environment, impacting the mucosal barrier. However, the role of zonulin, a modulator of epithelial tight junctions in GALT during HIV infection, remains poorly understood. Methods: We measured zonulin in serum and intestinal tissue sections from five treatment-naive (HIV⁺_NAIVE) and 10 cART-treated (HIV⁺_cART) HIV⁺ individuals, along with 11 controls (CTRL). We compared zonulin levels with clinical characteristics, inflammatory markers (IFN-α, CXCR3, and PD-1), and the viral reservoir in peripheral blood (PB) and terminal ileum (TI). Results: Upon HIV infection, TI was found to harbor more HIV DNA than PB. Circulating zonulin levels were highest in HIV⁺_NAIVE compared to HIV⁺_cART or CTRL. Surprisingly, in the gut tissue sections, zonulin levels were higher in CTRL than in HIV⁺ individuals. Elevated circulating zonulin levels were found to be correlated with CD4⁺T-cell depletion in PB and TI, and with intestinal IFN-α. Conclusions: The findings of this study indicate a shift in zonulin levels from the gut to the bloodstream in response to HIV infection. Furthermore, elevated systemic zonulin levels are associated with the depletion of intestinal CD4⁺ T cells and increased gut inflammation, suggesting a potential link between systemic zonulin and intestinal damage. Gaining insight into the regulation of gut tight junctions during HIV infection could offer valuable understanding for preventing NICM in PLWH. Full article

The luminal surface of the intestinal epithelium is protected by a vital mucus layer, which is essential for lubrication, hydration, and fostering symbiotic bacterial relationships. Replicating and studying this complex mucus structure in vitro presents considerable challenges. To address this, we developed a hydrogel-integrated millifluidic tissue chamber capable of applying precise apical shear stress to intestinal models cultured on flat or 3D structured hydrogel scaffolds with adjustable stiffness. The chamber is designed to accommodate nine hydrogel scaffolds, 3D-printed as flat disks with a storage modulus matching the physiological range of intestinal tissue stiffness (~3.7 kPa) from bioactive decellularized and methacrylated small intestinal submucosa (dSIS-MA). Computational fluid dynamics simulations were conducted to confirm a laminar flow profile for both flat and 3D villi-comprising scaffolds in the physiologically relevant regime. The system was initially validated with HT29-MTX seeded hydrogel scaffolds, demonstrating accelerated differentiation, increased mucus production, and enhanced 3D organization under shear stress. These characteristic intestinal tissue features are essential for advanced in vitro models as they critically contribute to a functional barrier. Subsequently, the chamber was challenged with human intestinal stem cells (ISCs) from the terminal ileum. Our findings indicate that biomimicking hydrogel scaffolds, in combination with physiological shear stress, promote multi-lineage differentiation, as evidenced by a gene and protein expression analysis of basic markers and the 3D structural organization of ISCs in the absence of chemical differentiation triggers. The quantitative analysis of the alkaline phosphatase (ALP) activity and secreted mucus demonstrates the functional differentiation of the cells into enterocyte and goblet cell lineages. The millifluidic system, which has been developed and optimized for performance and cost efficiency, enables the creation and modulation of advanced intestinal models under biomimicking conditions, including tunable matrix stiffness and varying fluid shear stresses. Moreover, the readily accessible and scalable mucus-producing cellular tissue models permit comprehensive mucus analysis and the investigation of pathogen interactions and penetration, thereby offering the potential to advance our understanding of intestinal mucus in health and disease. Full article

Introduction: Different robotic systems have been used widely in human surgery since 2000, but pediatric patients require some features that are lacking in the most frequently used robotic systems. Hypothesis: The Senhance^® robotic system is a safe and an effective device for use in infants and children that has some advantages over other robotic systems. Methods: All patients between 0 and 18 years of age whose surgery was amenable to laparoscopy were offered enrollment in this IRB-approved study. We assessed the feasibility, ease and safety of using this robotic platform in pediatric patients including: set-up time, operative time, conversions, complications and outcomes. Results: Eight patients, ranging from 4 months to 17 years of age and weighing between 8 and 130 kg underwent a variety of procedures including: cholecystectomy (3), inguinal herniorrhaphy (3), orchidopexy for undescended testes (1) and exploration for a suspected enteric duplication cyst (1). All robotic procedures were successfully performed. The 4-month-old (mo), 8 kg patient underwent an uneventful robotic exploration in an attempt to locate a cyst that was hidden in the mesentery at the junction of the terminal ileum and cecum, but ultimately the patient required an anticipated laparotomy to palpate the cyst definitively and to excise it completely. There was no blood loss and no complications. Robotic manipulation with the reusable 3 mm instruments proved successful in all cases. Conclusions: Our initial experience with the Senhance^® robotic platform suggests that this is a safe and effective device for pediatric surgery that is easy to use, and which warrants continued evaluation. Most importantly, there appears to be no lower age or weight restrictions to its use. Full article

The aim was to study the complementary effect between cereals and pulses on protein quality. The values for the digestible indispensable amino acid score (DIAAS) in cooked cereals and pulses, given alone, and blends of cooked cereals and pulses, were determined. True ileal digestibility (TID) values of amino acids for adult humans were obtained. It is difficult to determine ileal amino acid digestibility in humans directly, and for this reason, the growing pig is often used to obtain such values, as a preferred animal model. Seven growing pigs fitted with a T-cannula at the terminal ileum were allotted to a 7 × 6 incomplete Latin square with seven semi-synthetic diets (cooked mung bean, adzuki bean, millet, adlay, mung bean + millet, adzuki bean + adlay, and an N-free diet) and six 7-day periods. The mean TID values for crude protein differed significantly (p < 0.05), with millet having the highest digestibility (89.4%) and the adzuki bean/adlay mixture having the lowest (79.5%). For lysine, adzuki bean had the highest TID (90%) and millet had the lowest (70%). For the mean of all the amino acids, there was a significant (p < 0.05) effect of diet, with the TID ranging from 72.4% for the adzuki bean/adlay mixture to 89.9% for the adzuki beans. For the older child, adolescent, and adult, the DIAAS (%) was 93 for mung beans, 78 for adzuki beans, 22 for millet, 16 for adlay, and 66 for mung beans + millet, and 51 for adzuki beans + adlay. For mung beans, valine was first-limiting, and the SAA for adzuki beans, while lysine was first-limiting for the other foods. Chinese traditional diets, containing both cereals and pulses, are complementary for most, but not all of the indispensable amino acids. Full article

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. In addition, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated a catalogue of differentially expressed human transcripts encoded by 289 genes in 41 human tissues from 838 adult individuals of the Genotype-Tissue Expression project (GTEx, v8 release) and focused our analysis on relevant transcripts implicated in drug response. We detected significant sex-differentiated expression of 99 transcripts encoded by 59 genes in the tissues most relevant for human pharmacology (liver, lung, kidney, small intestine terminal ileum, skin not sun-exposed, and whole blood). Among them, as expected, we confirmed significant differences in the expression of transcripts encoded by the cytochromes in the liver, CYP2B6, CYP3A7, CYP3A5, and CYP1A1. Our systematic investigation on differences between male and female in the expression of drug response-related genes, reinforce the need to overcome the sex bias of clinical trials. Full article

The beneficial effects of human milk suppressing the development of intestinal pathologies such as necrotizing enterocolitis in preterm infants are widely known. Human milk (HM) is rich in a multitude of bioactive factors that play major roles in promoting postnatal maturation, differentiation, and the development of the microbiome. Previous studies showed that HM is rich in hyaluronan (HA) especially in colostrum and early milk. This study aims to determine the role of HA 35 KDa, a HM HA mimic, on intestinal proliferation, differentiation, and the development of the intestinal microbiome. We show that oral HA 35 KDa supplementation for 7 days in mouse pups leads to increased villus length and crypt depth, and increased goblet and Paneth cells, compared to controls. We also show that HA 35 KDa leads to an increased predominance of Clostridiales Ruminococcaceae, Lactobacillales Lactobacillaceae, and Clostridiales Lachnospiraceae. In seeking the mechanisms involved in the changes, bulk RNA seq was performed on samples from the terminal ileum and identified upregulation in several genes essential for cellular growth, proliferation, and survival. Taken together, this study shows that HA 35 KDa supplemented to mouse pups promotes intestinal epithelial cell proliferation, as well as the development of Paneth cells and goblet cell subsets. HA 35 KDa also impacted the intestinal microbiota; the implications of these responses need to be determined. Full article

Values for the digestible indispensable amino acid score (DIAAS) of a protein are based on true ileal amino acid (AA) digestibility values obtained in adult humans or in the growing pig as an animal model. An experiment was conducted using growing pigs to determine the true ileal digestibility (TID) values of AA in six cooked Chinese pulses (kidney bean, mung bean, adzuki bean, broad beans, peas and chickpeas). Each pulse was included in a diet as the only source of crude protein (CP). An N-free diet was given to allow determination of gut endogenous AA losses. Seven growing pigs each fitted with a T-cannula at the terminal ileum were allotted to a 7 by 6 incomplete Latin square with seven diets and six 7-d periods. The true digestibility values % for the total indispensable AA were higher (p < 0.001) for broad beans (87.3 ± 2.98) and lower (p < 0.001) for kidney bean (73.3 ± 4.84) than for the other pulses. For the older child (over 3 years), adolescent and adult, the DIAAS (%) was 88 for kidney bean, 86 for mung bean, 76 for chickpeas, 68 for peas, 64 for adzuki bean and 60 for broad beans. Full article

In mammalian small intestine, glucose is primarily absorbed via Na-dependent glucose co-transporter (SGLT1) on the brush border membrane (BBM) of absorptive villus cells. Malabsorption of nutrients (e.g., glucose) leads to malnutrition, a common symptom of inflammatory bowel disease (IBD), where the mucosa is characterized by chronic inflammation. Inducible nitric oxide (iNO) is known to be elevated in IBD mucosa. SAMP1/YitFc (SAMP1) mouse is a spontaneous model of chronic ileitis that develops lesions in its terminal ileum, very similar to human IBD. How SGLT1 may be affected in SAMP1 model of chronic ileitis is unknown. Ten-week-old SAMP1 mice with AKR mice as control were treated with N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) to inhibit iNO production. Intracellular NO levels were found to be increased in villus cells from SAMP1 mice. Moreover, SGLT1 and Na^+/K⁺-ATPase activities and BBM SGLT1 expression were significantly decreased. However, L-NIL treatment reduced the intracellular iNO production, and reversed both downregulated SGLT1 and Na⁺/K⁺-ATPase activities in SAMP1 mice. Inhibition of iNO by L-NIL treatment also significantly reversed the BBM SGLT1 protein expression in SAMP1 mice. L-NIL reversed the inflammation mediated downregulation of SGLT1 activity by restoring the BBM SGLT1 expression. Thus, regulation of SGLT1 in chronic ileitis is likely mediated by iNO. Full article

In obesity, increased absorption of dietary fat contributes to altered lipid homeostasis. In turn, dyslipidemia of obesity leads to many of the complications of obesity. Bile acids are necessary for the absorption of dietary fat. In the mammalian intestine, apical sodium-dependent bile acid cotransporter (ASBT; SLC10A2) is exclusively responsible for the reabsorption of bile acids in the terminal ileum. In rat and mice models of obesity and importantly in obese humans, ASBT was increased in ileal villus cells. The mechanism of stimulation of ASBT was secondary to an increase in ASBT expression in villus cell brush border membrane. The stimulation of ASBT was not secondary to the altered Na-extruding capacity of villus cells during obesity. Further, increased Farnesoid X receptor (FXR) expression in villus cells during obesity likely mediated the increase in ASBT. Moreover, enhanced FXR expression increased the expression of bile-acid-associated proteins (IBABP and OSTα) that are responsible for handling bile acids absorbed via ASBT in villus cells during obesity. Thus, this study demonstrated that in an epidemic condition, obesity, the dyslipidemia that leads to many of the complications of the condition, may, at least in part, be due to deregulation of intestinal bile acid absorption. Full article

Salmonella Typhimurium is an enteric pathogen that causes acute and chronic infections in humans and animals. One-week-old germ-free piglets were orally colonized/infected with the Salmonella Typhimurium LT2 strain or its isogenic rough ΔrfaL, ΔrfaG or ΔrfaC mutants with exactly defined lipopolysaccharide (LPS) defects. After 24 h, the piglets were euthanized and the colonization of the small intestine, translocations into the mesenteric lymph nodes, liver, spleen, lungs, and bacteremia, along with changes in the ileum histology, and transcription levels of the tight junction proteins claudin-1, claudin-2, and occludin were all assessed. Additionally, transcription levels of IL-8, TNF-α, and IL-10 in the terminal ileum, and their local and systemic protein levels were evaluated. Wild-type Salmonella Typhimurium showed the highest translocation, histopathological changes, upregulation of claudins and downregulation of occludin, transcription of the cytokines, intestinal IL-8 and TNF-α levels, and systemic TNF-α and IL-10 levels. Depending on the extent of the incompleteness of the LPS, the levels of the respective elements decreased, or no changes were observed at all in the piglets colonized/infected with Δrfa mutants. Intestinal IL-10 and systemic IL-8 levels were not detected in any piglet groups. This study provided foundational data on the gnotobiotic piglet response to colonization/infection with the exactly defined rough Salmonella Typhimurium LT2 isogenic mutants. Full article

Lactic acid bacteria (LAB) are Gram-positive bacteria that are natural inhabitants of the gastrointestinal (GI) tracts of mammals, including humans. Since Mechnikov first proposed that yogurt could prevent intestinal putrefaction and aging, the beneficial effects of LAB have been widely demonstrated. The region between the duodenum and the terminal of the ileum is the primary region colonized by LAB, particularly the Lactobacillus species, and this region is covered by a mucus layer composed mainly of mucin-type glycoproteins. The mucus layer plays a role in protecting the intestinal epithelial cells against damage, but is also considered to be critical for the adhesion of Lactobacillus in the GI tract. Consequently, the adhesion exhibited by lactobacilli on mucin has attracted attention as one of the critical factors contributing to the persistent beneficial effects of Lactobacillus in a constantly changing intestinal environment. Thus, understanding the interactions between Lactobacillus and mucin is crucial for elucidating the survival strategies of LAB in the GI tract. This review highlights the properties of the interactions between Lactobacillus and mucin, while concomitantly considering the structure of the GI tract from a histochemical perspective. Full article