Examining the Effects of 4He Exposure on the Gut-Brain Axis

Beyond low-Earth orbit, space radiation poses significant risks to astronaut health. Previous studies have shown that the microbial composition of the gastrointestinal (GI) microbiome changes upon exposure to high-linear energy transfer radiation. Interestingly, radiation-induced shifts in GI microbiota composition are linked to various neuropsychological disorders. Herein, we aimed to study changes in GI microbiota and behaviors of rats exposed to whole-body radiation (0, 5 or 25 cGy 4He, 250 MeV/n) at approximately 6 months of age. Fecal samples were collected 24 h prior to 4He irradiation and 24 h and 7 days postirradiation for quantitative PCR analyses to assess fecal levels of spore-forming bacteria (SFB), Bifidobacterium, Lactobacillus and Akkermansia. Rats were also tested in the social odor recognition memory (SORM) test at day 7 after 4He exposure. A subset of rats was euthanized 90 min after completion of the SORM test, and GI tissue from small intestine to colon were prepared for examining overall histological changes and immunohistochemical staining for serotonin (5-HT). No notable pathological changes were observed in GI tissues. Akkermansia spp. and SFB were significantly decreased in the 25 cGy group at 24 h and 7 days postirradiation compared to pre-exposure, respectively. Bifidobacterium and Lactobacillus spp. showed no significant changes. 5-HT production was significantly higher in the proximal small intestine and the cecum in the 25 cGy group compared to the sham group. The 25 cGy group exhibited deficits in recognition in SORM testing at day 7 postirradiation. Taken together, these results suggest a connection between GI microbiome composition, serotonin production, and neurobehavioral performance, and that this connection may be disrupted upon exposure to 25 cGy of 4He ions.

Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications

There have been many efforts to improve oral drug bioavailability and therapeutic efficacy and patient compliance. A variety of controlled-release oral delivery systems have been developed to meet these needs. Gastroretentive drug delivery technologies have the potential to achieve retention of the dosage form in the upper gastrointestinal tract (GIT) that can be sufficient to ensure complete solubilisation of the drugs in the stomach fluids, followed by subsequent absorption in the stomach or proximal small intestine. This can be beneficial for drugs that have an “absorption window” or are absorbed to a different extent in various segments of the GIT. Therefore, gastroretentive technologies in tandem with controlled-release strategies could enhance both the therapeutic efficacy of many drugs and improve patient compliance through a reduction in dosing frequency. The paper reviews different gastroretentive drug delivery technologies and controlled-release strategies that can be combined and summarises examples of formulations currently in clinical development and commercially available gastroretentive controlled-release products. The different parameters that need to be considered and monitored during formulation development for these pharmaceutical applications are highlighted.

ASSORTMENT ANALYSIS OF DRUGS FOR THE TREATMENT OF MILD AND MODERATE ULCERATIVE COLITIS

The article is devoted to the assortment analysis of 5-aminosalicylic acid drugs used for the treatment of mild and moderate ulcerative colitis. A brief description of dosage forms for oral and rectal administration used for the treatment of this disease is given. It is shown that therapeutic efficacy of the drug is associated with the concentration of the active substance in the large intestine. Therefore, in order to increase its effectiveness it is important to use such dosage forms that would help to prevent and reduce mesalazine absorption in the proximal small intestine and contribute to maximum release in the large intestine. It is shown that the rectal suspension of mesalazine, which is a first-line drug and is included in the list of essential medicines, is not produced in the Republic of Belarus. Special attention is paid to the possibility of expanding the range of mesalazine drugs if there is a possibility of extemporal suspension production from tablets presented in the assortment including a domestic manufacturer.

Small intestinal levels of the branched short-chain fatty acid isovalerate are elevated during infection with Heligmosomoides polygyrus and can promote helminth fecundity

Heligmosomoides polygyrus is a helminth which naturally infects mice and is widely used as a laboratory model of chronic small intestinal helminth infection. While it is known that infection with H. polygyrus alters the composition of the host’s bacterial microbiota, the functional implications of this alteration are unclear. We investigated the impact of H. polygyrus infection on short-chain fatty acid (SCFA) levels in the mouse intestine and sera. We found that helminth infection resulted in significantly upregulated levels of the branched SCFA isovaleric acid, exclusively in the proximal small intestine, which is the site of H. polygyrus colonization. We next set out to test the hypothesis that elevating local levels of isovaleric acid was a strategy used by H. polygyrus to promote its own fitness within the mammalian host. To test this, we supplemented the drinking water of mice with isovalerate during H. polygyrus infection and examined whether this affected helminth fecundity or chronicity. We did not find that isovaleric acid supplementation affected helminth chronicity, however, we found that it did promote helminth fecundity, as measured by helminth egg output in the feces of mice. Through antibiotic-treatment of helminth-infected mice, we found that the bacterial microbiota was required in order to support elevated levels of isovaleric acid in the proximal small intestine during helminth infection. Overall, our data reveal that during H. polygyrus infection there is a microbiota-dependent localized increase in the production of isovaleric acid in the proximal small intestine and this supports helminth fecundity in the murine host.

Temporal Dynamics of T Helper Populations in the Proximal Small Intestine after Oral Bovine Lactoferrin Administration in BALB/c Mice

Bovine lactoferrin (bLf), a component of milk and a dietary supplement, modulates intestinal immunity at effector and inductor sites. Considering the regional difference in intestinal compartments and the dynamics of local cytokine-producing cells in the gut across time, the aim of this work was to characterize the effects of bLf on the proximal small intestine in a BALB/c murine model of oral administration. Male BALB/c mice were treated with oral bLf vs. saline control as mock by buccal deposition for 28 days. Intestinal secretions were obtained at different time points and cells were isolated from Peyer’s patches (PP) and lamina propria (LP) of the proximal small intestine as representative inductor and effector sites, respectively. Total and specific anti-bLF IgA and IgM were determined by enzyme-immuno assay; the percentages of IgA+ and IgM+ plasma cells (PC) and cytokine-producing CD4+ T cells of PP and LP were analyzed by flow cytometry. We found that total and bLf-specific IgA and IgM levels were increased in the intestinal secretions of the bLf group in comparison to mock group and day 0. LP IgA+ PC and IgM+ PC presented an initial elevation on day 7 and day 21, respectively, followed by a decrease on day 28 in comparison to mock. Higher percentages of CD4+ T cells in LP were found in the bLf group. Cytokines-producing CD4+ T cells populations presented a pattern of increases and decreases in the bLf group in both LP and PP. Transforming growth factor beta (TGF-β)+ CD4+ T cells showed higher percentages after bLf administration with a marked peak at day 21 in both LP and PP in comparison to mock-treated mice. Oral bLf exhibits complex immune properties in the proximal small intestine, where temporal monitoring of the inductor and effector compartments reveals patterns of rises and falls of different cell populations. Exceptionally, TGF-β+ CD4+ T cells show consistent higher numbers after bLf intervention across time. Our work suggests that isolated measurements do not show the complete picture of the modulatory effects of oral bLf in immunological sites as dynamic as the proximal small intestine.

Targeting the Intestinal Barrier to Prevent Gut-Derived Inflammation and Disease: A Role for Intestinal Alkaline Phosphatase

<b><i>Background:</i></b> Intestinal alkaline phosphatase (IAP) as a tissue-specific isozyme of alkaline phosphatases is predominantly produced by enterocytes in the proximal small intestine. In recent years, an increasing number of pathologies have been identified to be associated with an IAP deficiency, making it very worthwhile to review the various roles, biological functions, and potential therapeutic aspects of IAP. <b><i>Summary:</i></b> IAP primarily originates and acts in the intestinal tract but affects other organs through specific biological axes related to its fundamental roles such as promoting gut barrier function, dephosphorylation/detoxification of lipopolysaccharides (LPS), and regulation of gut microbiota. <b><i>Key Messages:</i></b> Numerous studies reporting on the different roles and the potential therapeutic value of IAP across species have been published during the last decade. While IAP deficiency is linked to varying degrees of physiological dysfunctions across multiple organ systems, the supplementation of IAP has been proven to be beneficial in several translational and clinical studies. The increasing evidence of the salutary functions of IAP underlines the significance of the naturally occurring brush border enzyme.

Contribution of Capsule Endoscopy Early in a Bleeding Episode to Treatment of Small Bowel Angioectasia: A Case Report

Background: Recent advances in endoscopic devices such as small bowel capsule endoscopy and balloon-assisted endoscopy have improved the level of medical care for small bowel bleeding. However, treating small bowel angioectasia remains challenging because repeated intermittent bleeding can occur from the multiple minute lesions (about 1 mm in size) that develop in a synchronous and metachronous manner. Here, we report a case of small bowel angioectasia in which capsule endoscopy performed early in a bleeding episode contributed to treatment. Case Summary: A 66-year-old man with suspected small bowel bleeding underwent small bowel capsule endoscopy and balloon-assisted endoscopy with argon plasma coagulation hemostasis for a small intestinal angioectasia. Because small bowel bleeding recurred intermittently after the treatment, small bowel capsule endoscopy and balloon-assisted endoscopy were repeated when there was no bleeding, but no abnormalities were found. Subsequent small bowel capsule endoscopy during a bleeding episode revealed bloody intestinal fluid in the proximal small intestine. Peroral balloon-assisted endoscopy was performed 2 days after SBCE for detailed observation of the small intestinal mucosa at the suspected bleeding site, and there a 1-mm Dieulafoy’s lesion with no active bleeding was identified. We performed argon plasma coagulation, and no bleeding was observed thereafter. Conclusions: Small bowel capsule endoscopy immediately after bleeding onset can identify the bleeding source of multiple minute lesions in small bowel angioectasia.

Recurrent trichobezoar in a patient with Rapunzel syndrome

Rapunzel syndrome is a condition where a trichobezoar is formed in the stomach and proximal intestine due to hair ingestion. A 6-year-old girl presented to emergency department with abdominal pain, vomiting and a palpable epigastric mass. Laparotomy was performed for gastric foreign body; a trichobezoar that filled the stomach, duodenum and proximal small intestine was removed. Postoperative course was uncomplicated; the patient was discharged for further out-patient follow-up and psychological care. After 7 months, the girl presented with a recurrence. A recurrent trichobezoar was removed via laparotomy. The girl was started on psychiatric treatment and iron substitution for anaemia. Ten weeks after discharge, follow-up gastroscopy was negative for gastric foreign body. There are no guidelines for follow-up after trichobezoar removal. Since the disease may be recurrent, follow-up endoscopy should be considered in order to enable an early diagnosis and less invasive treatment.

P30: PYY HORMONE UPREGULATES PROXIMAL GLP-1 RELEASE AFTER ROUX EN-Y GASTRIC BYPASS

Introduction Nowadays Roux-en-Y gastric bypass (RYGB) has provided a powerful treatment for type 2 diabetes mellitus. Nevertheless how anatomical arrangements after RYGB influeces entero-hormonal response and the role of Peptide Tyrosine Tyrosine (PYY) in the restoration of normoglycaemia are still not clear. MATERIAL AND Method We demonstrate that PYY plasma levels showed a remarkable peak, around thirty minutes earlier than GLP-1 or GIP, after mixed-meal administration in non obese Goto – Kakizaki RYGB-operated rats . Also, we found that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Result Histologically the number of GLP-1 positive cells number appeared to increase in the three segments of the small intestine:duodenum jejunum and ileum in GK RYGB-operated rats beyond early presence of nutrient stimulation in the ileum. But nevertheless, PYY positive cell numbers appeared to increased only in the ileum. Conclusion Taking together this findings suggest an earlier central role for PYY in gut hormone regulation after RYGB in our model, contributing to GLP-1 and GIP release and support the existence of enteroendocrine communication routes between the distal and proximal small intestine. Take-home message Enterohormones release changes after bariatric surgery due to the consequences in nutrients flow. The GLP-1 release is increased and we report its related to the PYY regulation.

Celiac Disease

This chapter reveals and discusses a case involving celiac disease (CD). CD is a common, lifelong, genetically-based autoimmune disorder that causes inflammation of the proximal small intestine. This disease is triggered by eating foods containing gluten, which causes intestinal discomfort. Gluten is a protein that is found naturally in wheat, barley, and rye and is common in foods such as bread, pasta, cookies, and cakes. Many pre-packaged foods, lip balms and lipsticks, hair and skin products, toothpaste and vitamin and nutrient supplements contain gluten, although it is rarely found in medicine. The key to living with CD is to follow a gluten-free diet. This case shows the role of medical nutrition therapy in managing and preventing the undesirable symptoms of CD. Moreover, it allows dietetic professionals to assess celiac patients' conditions and provide them with relief from undesirable symptoms, while also establishing an effective follow-up plan with each patient.