Intestinal Transit Research Articles

Disruption of the microbiota-gut-brain axis is a defining characteristic of the α-Gal A (-/0) mouse model of Fabry disease

ABSTRACT Fabry disease (FD) is an X-linked metabolic disease caused by a deficiency in α-galactosidase A (α-Gal A) activity. This causes accumulation of glycosphingolipids, especially globotriaosylceramide (Gb3), in different cells and organs. Neuropathic pain and gastrointestinal (GI) symptoms, such as abdominal pain, nausea, diarrhea, constipation, and early satiety, are the most frequent symptoms reported by FD patients and severely affect their quality of life. It is generally accepted that Gb3 and lyso-Gb3 are involved in the symptoms; nevertheless, the origin of these symptoms is complex and multifactorial, and the exact mechanisms of pathogenesis are still poorly understood. Here, we used a murine model of FD, the male α-Gal A (-/0) mouse, to characterize functionality, behavior, and microbiota in an attempt to elucidate the microbiota-gut-brain axis at three different ages. We provided evidence of a diarrhea-like phenotype and visceral hypersensitivity in our FD model together with reduced locomotor activity and anxiety-like behavior. We also showed for the first time that symptomology was associated with early compositional and functional dysbiosis of the gut microbiota, paralleled by alterations in fecal short-chain fatty acid levels, which partly persisted with advancing age. Interestingly, most of the dysbiotic features suggested a disruption of gut homeostasis, possibly contributing to accelerated intestinal transit, visceral hypersensitivity, and impaired communication along the gut-brain axis.

Genetic Approaches to Increase Arabinoxylan and β-Glucan Content in Wheat.

Wheat is one of the three staple crops feeding the world. The demand for wheat is ever increasing as a relatively good source of protein, energy, nutrients, and dietary fiber (DF) when consumed as wholemeal. Arabinoxylan and β-glucan are the major hemicelluloses in the cell walls and dietary fiber in wheat grains. The amount and structure of DF varies between grain tissues. Reducing post-prandial glycemic response as well as intestinal transit time and contribution to increased fecal bulk are only a few benefits of DF consumption. Dietary fiber is fermented in the colon and stimulates growth of beneficial bacteria producing SCFA, considered responsible for a wide range of health benefits, including reducing the risk of heart disease and colon cancer. The recommended daily intake of 25-30 g is met by only few individuals. Cereals cover nearly 40% of fiber in the Western diet. Therefore, wheat is a good target for improving dietary fiber content, as it would increase the fiber intake and simultaneously impact the health of many people. This review reflects the current status of the research on genetics of the two major dietary fiber components, as well as breeding approaches used to improve their quantity and quality in wheat grain.

Association between clinical and surgical variables with postoperative outcomes in patients treated for intestinal obstruction for non-malignant conditions: a cross-sectional study

Intestinal obstruction is considered a frequent surgical pathology related to previous surgical procedures. Many different factors can lead to different outcomes when surgical management is needed. Therefore, we aim to describe the factors related to morbidity and mortality in surgical management of IO in a single-center experience. Retrospective observational study with a prospective database, in which we described patients who underwent surgical management due to intestinal obstruction between 2004 and 2015. Demographics, perioperative data, surgical outcomes, morbidity, and mortality were described. 366 patients were included. Female were 54.6%. Mean age was 61.26. Laparoscopic approach was done in 21.8% and the conversion rate was 17.2%. Intestinal resection was performed in 37.9% of the cases. Postoperative complications were observed in 18.85%. Reintervention and mortality were 9.5% and 4.1% respectively. Laparoscopic approach shows lesser time of intestinal transit (mean 28.67 vs. mean 41.95 h), and restart of oral intake after surgery (mean 96.06 vs. mean 119.65) compared with open approach. Increased heart rate and intensive care unit length of stay were related with mortality (p 0.01 and 0.000 respectively). For morbidity, laparotomy and need and duration of ICU stay were related with any complication statistically significant (p 0.02, 0.008, 0.000 respectively). Patients with increased heart rate in the emergency room, decreased amount of intravenous fluids, need and higher length of stay in the intensive care unit, and delay in resuming oral intake after surgery appear to have poor outcomes. Laparoscopic approach seems to be a safe and feasible approach for intestinal obstruction in selected patients.

Arecoline alleviated loperamide induced constipation by regulating gut microbes and the expression of colonic genome

This study aimed to investigate the effects of arecoline on constipation by intervening at different times to explore its preventive and therapeutic effects. Symptoms related to constipation, gut microbes, short-chain fatty acid (SCFA) content in the cecum, and gene expression in the colon were measured to examine the effect of arecoline on relieving constipation. The results showed that arecoline intervention alleviated loperamide-induced constipation, as evidenced by significantly shortened intestinal transit time, increased fecal water content, improved small bowel propulsion, and increased defecation frequency. In addition, arecoline significantly reduced the levels of gastrointestinal regulatory peptides such as somatostatin and vasoactive intestinal peptide in the serum, thereby regulating intestinal peristalsis. Histopathological analysis showed that arecoline ameliorated intestinal injury caused by constipation. Gut microbial analysis indicated that arecoline altered the taxonomic composition and levels of its metabolite SCFAs in the gut microbiota. Furthermore, the colonic transcriptome results indicated that genes expression related to intestinal diseases were significantly down-regulated by arecoline intervention. In conclusion, the results of the correlation analysis propose a possible mechanism of arecoline in alleviating constipation by modulating the gut microbes and their metabolites and regulating the gut genome.

A homozygous missense variant in the PLCB4 gene causes severe phenotype of auriculocondylar syndrome type 2.

Auriculocondylar syndrome (ARCND) is a rare craniofacial birth defect characterized by malformations in the mandible and external ear (Question Mark Ear). Genetically, three distinct subtypes of ARCND (ARCND1, ARCND2, and ARCND3) have been identified. ARCND2 is linked to pathogenic variants in the PLCB4 gene (phospholipase C β4). PLCB4 is a key effector of the EDN1-EDNRA pathway involved in craniofacial development via the induction, migration, and maintenance of neural crest cells. ARCND2 is typically inherited in an autosomal dominant pattern, with recessive inheritance pattern being rare. In this study, we report the first homozygous missense variant (NM_000933.4: c.2050G>A: p.(Gly684Arg)) in the PLCB4 gene causing ARCND in a 3-year-old patient with a severe clinical phenotype of the syndrome. The patient presented with typical craniofacial ARCND features, in addition to intestinal transit defect, macropenis, and hearing loss. These findings further delineate the phenotypic spectrum of ARCND associated with autosomal recessive PLCB4 loss of function variants. Notably, our results provide further evidence that these variants can result in a more severe and diverse manifestations of the syndrome. Clinicians should consider the rare features of this condition for better management of patients.

L. rhamnosus CNCM I-3690 survival, adaptation, and small bowel microbiome impact in human

ABSTRACT Fermented foods and beverages are a significant source of dietary bacteria that enter the gastrointestinal (GI) tract. However, little is known about how these microbes survive and adapt to the small intestinal environment. Colony-forming units (CFU) enumeration and viability qPCR of Lacticaseibacillus rhamnosus CNCM I-3690 in the ileal effluent of 10 ileostomy subjects during 12-h post consumption of a dairy product fermented with this strain demonstrated the high level of survival of this strain during human small intestine passage. Metatranscriptome analyses revealed the in situ transcriptome of L. rhamnosus in the small intestine, which was contrasted with transcriptome data obtained from in vitro cultivation. These comparative analyses revealed substantial metabolic adaptations of L. rhamnosus during small intestine transit, including adjustments of carbohydrate metabolism, surface-protein expression, and translation machinery. The prominent presence of L. rhamnosus in the effluent samples did not elicit an appreciable effect on the composition of the endogenous small intestine microbiome, but significantly altered the ecosystem’s overall activity profile, particularly of pathways associated with carbohydrate metabolism. Strikingly, two of the previously recognized gut-brain metabolic modules expressed in situ by L. rhamnosus (inositol degradation and glutamate synthesis II) are among the most dominantly enriched activities in the ecosystem’s activity profile. This study establishes the survival capacity of L. rhamnosus in the human small intestine and highlights its functional adjustment in situ, which we postulate to play a role in the probiotic effects associated with this strain.

Gastrointestinal Transit Times in Health as Determined Using Ingestible Capsule Systems: A Systematic Review.

Ingestible capsule (IC) systems can assess gastrointestinal (GI) transit times as a surrogate for gut motility for extended periods of time within a minimally invasive, radiation-free and ambulatory setting. A literature review of IC systems and a systematic review of studies utilizing IC systems to measure GI transit times in healthy volunteers was performed. Screening for eligible studies, data extraction and bias assessments was performed by two reviewers. A narrative synthesis of the results was performed. The literature review identified 23 different IC systems. The systematic review found 6892 records, of which 22 studies were eligible. GI transit time data were available from a total of 1885 healthy volunteers. Overall, seventeen included studies reported gastric emptying time (GET) and small intestinal transit time (SITT). Colonic transit time (CTT) was reported in nine studies and whole gut transit time (WGTT) was reported in eleven studies. GI transit times in the included studies ranged between 0.4 and 15.3 h for GET, 3.3-7 h for SITT, 15.9-28.9 h for CTT and 23.0-37.4 h for WGTT. GI transit times, notably GET, were influenced by the study protocol. This review provides an up-to-date overview of IC systems and reference ranges for GI transit times. It also highlights the need to standardise protocols to differentiate between normal and pathological function.

Assessment of phytochemicals, antioxidant properties, and in vivo antidiarrheal activity of date palm (Phoenix dactylifera L.)

ABSTRACT Date palm (Phoenix dactylifera L.) has a significant role in our daily life due to its diverse nutritional composition and potential health benefits. This study was designed to evaluate the phytochemicals, antioxidant, and antidiarrheal potential of various extracts of Ajwa whole fruit, date palm pit, and flesh. The extracts with the highest phytochemical quantities were further subjected to bio-assay assessment against castor oil-induced diarrhea using different animal models. The results indicated that Ajwa whole fruit extract (AWFE) exhibited higher amount of total phenolic contents (TPC: 36 ± 16 mg/g GAE), total flavonoid contents (TFC: 360 ± 135 mg/g RE), and 2, 2-diphenyl-1-picrylhydrazyl (DPPH: 60 ± 7%) in hydro-ethanolic extracts. In vivo results revealed that Ajwa whole fruit 60% hydro-ethanolic extract at high dose (2000 mg/kg) showed significantly (p < .05) highest protective effect against diarrheal changes in mice. In case of AWFE, the intestinal contents % inhibition was slightly higher (72%) as compared to that of loperamide control (70%). High dose of Ajwa whole (2000 mg/kg) demonstrated less effectiveness (66 ± 11%) in comparison with loperamide (78 ± 8%) regarding % inhibition of fluid accumulation in enteropooling studies. High dose (2000 mg/kg) of Ajwa also reduced intestinal transit time by decreasing the % distance (53 ± 1%) in comparison with loperamide (57 ± 1%). The % inhibition of charcoal meal traveling of AWFE (38 ± 2%) was also significantly higher as compared to loperamide (26 ± 1%). The findings of the current study reveal that AWFE might be consumed as an ingredient in daily food products to counter effect the symptoms of diarrhea.

Effects of Bit Chewing on Gastric Emptying, Small Intestinal Transit, and Orocecal Transit Times in Clinically Normal Horses.

Ileus is a common life-threatening problem in horses, and currently available treatments may be ineffective. The purpose of this study was to determine whether bit chewing, a form of sham feeding, decreases the gastric emptying time (GET), small intestinal transit time (SITT), and total orocecal transit time (OCTT) in clinically normal horses in a prospective crossover study. Nine healthy horses were acclimated and fed a standardized diet. Following 24 h of fasting, self-contained video endoscopy capsules and acetaminophen were administered into the stomach via a nasogastric tube. Each horse underwent experimental (bit chewing for 20 min every 6 h) or control (no bit chewing) conditions, with a 3-week minimum washout period between conditions. The horses were enrolled in either part of the study until all video capsules were retrieved and/or 30 days lapsed. The video capsules were recovered from manure, and GET, SITT, and OCTT were determined from a video analysis. Bit chewing significantly decreased OCTT (p = 0.015) compared to the control conditions. Bit chewing decreased GET and SITT, but the differences were not significant. The mean (median) times determined via the video capsule analysis for the bit-chewing conditions were as follows: GET, 2.34 h (2.86 h); SITT, 3.22 h (3.65 h); and OCTT, 5.13 h (6.15 h), and for the control conditions, they were as follows: GET, 3.93 h (5 h); SITT, 3.79 h (4.4 h); and OCTT, 8.02 h (9.92 h). Bit chewing decreased OCTT in healthy horses. Because this segment of the gastrointestinal tract is frequently affected by ileus, bit chewing may be a safe and inexpensive intervention for that condition in horses. Further investigation in clinical patients with ileus is warranted.

Effect of deep needling "Tianshu" (ST25) on colonic motility in rats with slow transit constipation

To observe the effect of acupuncture of "Tianshu"(ST25) at different depths on colonic transportation function, expressions of colonic substance P (SP) and interstitial cells of Cajal (ICC) in rats with slow transit constipation (STC), so as to explore its mechanisms underlying improvement of STC．. Fifty male Wistar rats were selected and randomly divided into control，STC model，conventional acupuncture，deep needling group 1 and deep needling group 2 groups，with 10 rats in each group．The STC model was established by gavage of 1 mg/mL compound diphenoxylate suspension (10 mg/kg), once every other day for 21 days, and rats of the control group were given the same dose of distilled water by gavage．EA (2 Hz, 2 mA) was applied to "Tianshu"(ST25), with the acupuncture needle inserted to a depth of 3 mm for rats of the conventional acupuncture group, 4.5 mm for those of deep needling group 1, and 10 mm for those of the deep needling group 2. The acupuncture needle was twirled for 1 min, then retained for 15 min each time, once a day for 15 consecutive days．Following modeling, rats of the 4 groups and the control group received gavage of active carbon 2 mL (100 g/L) for observing the excretion time of the first black stool grain to assess the intestinal transit function. The colonic myoelectric activities (frequency and amplitude) were recorded by using BIOPAC multichannel physiograph. The immunoactivity of SP and c-kit (a transmembrane protein kinase for identification of ICC) of colonic musculature was detected by immunohistochemistry. Compared with the control group，the time of excretion of the first black stool grain, and the amplitude of colonic electromyogram (EMG) were significantly increased (P<0.01), while the frequency of EMG, expressions of SP and c-kit (ICC) were significantly decreased in the model group (P<0.01). In contrast to the model group, both deep needling group 1 and 2 had a decrease in the time of excretion of the first black stool grain, and amplitude of intestinal EMG, and an increase of frequency of intestinal EMG, and immunoactivity of SP and c-kit (P<0.01). The effect of deep needling 2 is superior to that of deep needling 1 in reducing the time of excretion of the first black stool grain (P<0.05), lowering the amplitude of EMG of the gut smooth muscle (P<0.05) and in increasing the frequency of EMG (P<0.05) and the expressions of SP and c-kit (P<0.05). No significant changes were found in the levels of frequency and amplitude of EMG, and expressions of SP and c-kit after routine needling in comparison with the model group (P>0.05), except the excretion time of the first black stool grain (P<0.05). Deep needling at ST25 at depth of 4.5 mm and 10 mm，especially at depth of 10 mm，has a significant effect in promoting gut motility to ameliorate constipation in rats with STC, which may be related to its function in up-regulating the expressions of SP and ICC activity.

Utilization of Gum Arabic as a Gelatine Substitute in Halal Watermelon (Citrullus lanatus) Pastille

Gelatine is widely used in pharmaceutical and food ingredient that is crucial in most Halal research. Non-halal gelatine accounts for 90% of the world's supply, which is typically taken from animals (bovine and porcine). The expanding and profitable halal, kosher and vegetarian markets (including Hindu) represent a substantial interest in gelatine substitution. Gelatine (G), a versatile hydrocolloid, is a significant ingredient in the confectionary industry due to its gel formation, high water-binding capacity, thickening, colloidal function, and adhesion/cohesion. Gum arabic (GA), a key hydrocolloid used in pastille manufacture, works as a stabilizer and fat emulsifier. The main objective of this study was to ascertain the effect of gum arabic and gelatine substitution on the physicochemical properties, antioxidant activity and sensory acceptability of halal watermelon (Citrullus lanatus) pastille. pH analysis, total soluble solid (TSS), texture profile analysis (TPA), colour, water activity (aw), melting point, calorie content, antioxidant activity by 2,2- diphenyl-2-picrylhydrazyl (DPPH), mineral content, proximate composition as well as sensory acceptability test were conducted on five different samples {A (0%GA:16%G); B (4%GA:12%G); C (8%GA:8%G); D (12%GA:4%G); and E (16%GA:0%G), respectively. The ideal formulation in terms of physicochemical qualities, antioxidant activity, and sensory acceptance was a sample with 12% gum arabic and 4% gelatine. Also, high antioxidant activity (44.72±3.76), low fat content (0.44 ± 0.27%) and calories (3054.23 ± 6.55cal/g) compared to other samples. The crude fibre and carbohydrate, which were (1.14 ± 0.08%) and (70.68%) were an advantage of this sample as both nutrients are essential in food due to their role to absorb water, assist in intestinal transit and provide roughage for the bowel. The sensory test that the 12% gum arabic and 4% of gelatine sample was most accepted compared to other samples. Gum arabic is a halal substance that can be recommended to produce gelatine alternatives in the pharmaceutical and food industries.

Effectiveness of vonoprazan-based regimens compared with proton pump inhibitor-based regimens as first-line Helicobacter pylori agents.

In this study, we compared the success rate of eradicating Helicobacter pylori (H. pylori) in adults and children using vonoprazan (VPZ)-based H. pylori regimens to that of proton pump inhibitors (PPIs). In Japan, the success rate of a VPZ-based regimen as first-line therapy was lower in children than in adults. Compared with adults, children around puberty have higher CYP2C19 and CYP3A4 enzymatic activity to metabolize PPIs and VPZ. Further, children generally have shorter intestinal transit times than adults and may absorb antibiotics to a lesser extent. When comparing success rates of pediatric and adult eradication therapy using VPZ, it is very important to maintain a higher intragastric pH with sufficient gastric acid suppression to maintain H. pylori in a replicating state and amoxicillin and clarithromycin in the intestinal tract for as long as possible by reducing diarrhea as a side effect. Based on the above, it is reasonable that VPZ, which can suppress stomach acids more strongly than PPI, is a more relevant H. pylori eradication therapy.

Microbial metabolite p-cresol inhibits gut hormone expression and regulates small intestinal transit in mice.

p-cresol is a metabolite produced by microbial metabolism of aromatic amino acid tyrosine. p-cresol and its conjugated forms, p-cresyl sulfate and p-cresyl glucuronide, are uremic toxins that correlate positively with chronic kidney disease and diabetes pathogenesis. However, how p-cresol affects gut hormones is unclear. Here, we expose immortalized GLUTag cells to increasing concentrations of p-cresol and found that p-cresol inhibited Gcg expression and reduced glucagon-like peptide-1 (GLP-1) secretion in vitro. In mice, administration of p-cresol in the drinking water for 2 weeks reduced the transcript levels of Gcg and other gut hormones in the colon; however, it did not affect either fasting or glucose-induced plasma GLP-1 levels. Furthermore, it did not affect glucose tolerance but promoted faster small intestinal transit in mice. Overall, our data suggest that microbial metabolite p-cresol suppresses transcript levels of gut hormones and regulates small intestinal transit in mice.

Endoscopic reversal of roux-en-Y gastric bypass prevents worsening of nutritional outcomes in patients with severe malnutrition

Roux-en-Y gastric bypass (RYGB) can precipitate protein-calorie malnutrition and micronutrient deficiencies. Sonographically guided endoscopic reversal (ER) via deployment of a stent from the gastric pouch to the remnant stomach in RYGB anatomy has emerged as a novel option for increasing both intestinal transit time and absorptive surface area. In this investigation, short-term nutritional outcomes after ER of a RYGB in patients (age ≥ 18) with severe protein-calorie malnutrition from a single academic health center in Minneapolis, Minnesota over a seven-year period (2015-2021) were retrospectively reviewed pre-procedurally, and at six and twelve months post-procedurally. 17 patients underwent ER for severe protein-calorie malnutrition, or dependence on tube feeds (TF) or total parenteral nutrition (TPN). At 6 months post-ER, two patients were no longer malnourished and only on oral nutrition; three patients were liberated from TPN. Laboratory markers of protein-calorie malnutrition, renal function, and micronutrients were not significantly different at six- or twelve-month follow-up (P &amp;gt; 0.05). In all patients, access to the gastric remnant was maintained via stent placement through the gastric pouch or proximal Roux limb throughout the study period and no complications were noted after ER. Despite the small sample size, this investigation revealed that ER of RYGB may prevent progressive deleterious weight loss, and worsening macro- and micro-nutrient deficiencies, though improvement in weight and nutritional parameters was not observed. Overall, ER was found to be a nuanced and safe, advanced technique useful for when remnant access is desired in RYGB patients.

Review: Methods and biomarkers to investigate intestinal function and health in pigs.

Society is becoming increasingly critical of animal husbandry due to its environmental impact and issues involving animal health and welfare including scientific experiments conducted on farm animals. This opens up two new fields of scientific research, the development of non- or minimally invasive (1) methods and techniques using faeces, urine, breath or saliva sampling to replace existing invasive models, and (2) biomarkers reflecting a disease or malfunction of an organ that may predict the future outcome of a pig's health, performance or sustainability. To date, there is a paucity of non- or minimally invasive methods and biomarkers investigating gastrointestinal function and health in pigs. This review describes recent literature pertaining to parameters that assess gastrointestinal functionality and health, tools currently used to investigate them, and the development or the potential to develop new non- and minimally invasive methods and/or biomarkers in pigs. Methods described within this review are those that characterise gastrointestinal mass such as the citrulline generation test, intestinal protein synthesis rate, first pass splanchnic nutrient uptake and techniques describing intestinal proliferation, barrier function and transit rate, and microbial composition and metabolism. An important consideration is gut health, and several molecules with the potential to act as biomarkers of compromised gut health in pigs are reported. Many of these methods to investigate gut functionality and health are considered 'gold standards' but are invasive. Thus, in pigs, there is a need to develop and validate non-invasive methods and biomarkers that meet the principles of the 3 R guidelines, which aim to reduce and refine animal experimentation and replace animals where possible.

Evaluation of the effect of Prithvi Mahabhuta (earth element) on intestinal transit time in Swiss albino mice

Background: Pugaphala (fruit of Areca catechu Linn.) and Udumbara Twaka (bark of Ficus glomerata Roxb.) are popular for their medicinal properties. Both drugs are used in a variety of compound formulations in Ayurveda. On the basis of their Rasa Panchaka (five factors of substance), pharmacognostical, and pharmaceutical research, Pugaphala and Udumbara Twaka were chosen as Prithvi Mahabhuta (earth element) dominant drugs in the current study. Aim: The aim of this study was to assess the impact of Prithvi Mahabhuta-dominating Dravya, Pugaphala, and Udumbara Twaka on intestinal transit time in Swiss albino mice. Materials and methods: A total of 18 Swiss albino mice were divided into three groups of six in each. Pugaphala and Udumbara Twaka were administered in mice in doses of 260 mg/kg and 520 mg/kg, respectively. Results: The result shows that both the drugs significantly reduce intestinal motility due to their Guna (properties) as Ruksha (dry), Vishada (nonslimy), Sthira (stable), Sheeta (cold), and Kashaya Rasa (astringent taste) of Prithvi Mahabhuta; however, Udumbara sample is found to be more efficient. Conclusion: The dominance of Prithvi Mahabhuta is thus confirmed by pharmacological studies in both Pugaphala and Udumbara Twaka, and it is also confirmed that Udumbara Twaka has more Parthiva dominancy than Pugaphala Churna. The Stambhana effect of Prithvi Mahabhuta on intestinal motility can be assessed by latency of onset of white-colored fecal matter in mice.

Evaluation of acute and sub-chronic oral toxicities of Neoneaster in rats.

Jaundice is a condition caused by the elevation of bilirubin level in the blood. Due to the neurological and neurodevelopmental sequalae of jaundice in newborns, the high cost of the treatment, and the side effects of the currently used therapies, novel therapeutically approaches are needed. Purgative manna (Shir-e-Khesht) has been used in Persian traditional medicine to reduce serum bilirubin levels of neonates. Neoneaster® is a natural health product formulated by a unique method from the manna of Cotoneaster nummularius Fisch. & C.A.Mey. for treating neonatal jaundice and managing constipation. The main component of Neoneaster®, mannitol, is an osmotic laxative which could increase intestinal transit and reduce the re-absorption of bilirubin in the enterohepatic cycle. We conducted this study to investigate acute and sub-chronic oral toxicities of Neoneaster in Wistar rats. In the acute oral toxicity test, based on OECD 423 we administered Neoneaster to the Wistar rats at doses of 5, 50, 300, and 2000mg/kg(OECD, 2002). Toxicological effects, including mortality and behavioral changes, were recorded for 14 days and compared to the control group. We also carried out histopathological assessments of the tissues of liver, heart, kidney, and spleen after this period. To evaluate sub-chronic toxicity, while administering 2000mg/kg of Neoneaster daily to the Wistar rats, we recorded for changes in mortality and behavior for 45 days and compared these to the values of the control group. We also carried out biochemical, hematological, and histopathological assessments after this period. In both acute and sub-chronic oral toxicity tests, no mortalities, behavioral abnormalities, and histological signs of toxicity was observed in any of the administered doses in comparison to the control group. The percentage of weight gains in acute toxicity test and the weight gain in sub-chronic test were not significant (P>0/05). There were also no significant differences in hematological and biochemical markers (P>0/05). Based on our finding, Neoneaster can be classified as category 5 in the Globally Harmonized Chemical Classification and Labeling System (GHS) as its Lethal Dose 50 (LD50) is higher than 2000mg/kg. This study suggests that Neoneaster is safe and can be classified as category 5 in the GHS system.

Ultraprocessed Foods and Obesity Risk: A Critical Review of Reported Mechanisms.

Epidemiologic evidence supports a positive association between ultraprocessed food (UPF) consumption and body mass index. This has led to recommendations to avoid UPFs despite very limited evidence establishing causality. Many mechanisms have been proposed, and this review critically aimed to evaluate selected possibilities for specificity, clarity, and consistency related to food choice (i.e., low cost, shelf-life, food packaging, hyperpalatability, and stimulation of hunger/suppression of fullness); food composition (i.e., macronutrients, food texture, added sugar, fat and salt, energy density, low-calorie sweeteners, and additives); and digestive processes (i.e., oral processing/eating rate, gastric emptying time, gastrointestinal transit time, and microbiome). For some purported mechanisms (e.g., fiber content, texture, gastric emptying, and intestinal transit time), data directly contrasting the effects of UPF and non-UPF intake on the indices of appetite, food intake, and adiposity are available and do not support a unique contribution of UPFs. In other instances, data are not available (e.g., microbiome and food additives) or are insufficient (e.g., packaging, food cost, shelf-life, macronutrient intake, and appetite stimulation) to judge the benefits versus the risks of UPF avoidance. There are yet other evoked mechanisms in which the preponderance of evidence indicates ingredients in UPFs actually moderate body weight (e.g., low-calorie sweetener use for weight management; beverage consumption as it dilutes energy density; and higher fat content because it reduces glycemic responses). Because avoidance of UPFs holds potential adverse effects (e.g., reduced diet quality, increased risk of food poisoning, and food wastage), it is imprudent to make recommendations regarding their role in diets before causality and plausible mechanisms have been verified.

THERAPEUTIC POTENTIAL OF FUNCTIONAL PRODUCT BASED ON WILD EDIBLE MUSHROOMS

Food supplements have proven their effectiveness through the support offered to administer certain drugs and their ability to determine the prevention of degenerative diseases. The correlation of assay methods with individual-level observations is essential in understanding the effect of biopharmaceuticals as a useful tool for long-term homeostasis preservation. This paper aimed to present essential aspects related to using wild edible mushrooms as functional supplements in type 2 diabetes and associated cardiovascular diseases. The product RoBioMush was presented as a result of the scientific data applied within the university, and the effects recorded after the administration of the product to the target groups were highlighted. Thus, the administration of RoBioMush had as its main effect the regulation of intestinal transit, a fact demonstrated by the researched modulation process previously in an in vitro study.

Dedicated macrophages organize and maintain the enteric nervous system.

Correct development and maturation of the enteric nervous system (ENS) is critical for survival1. At birth, the ENS is immature and requires considerable refinement to exert its functions in adulthood2. Here we demonstrate that resident macrophages of the muscularis externa (MMϕ) refine the ENS early in life by pruning synapses and phagocytosing enteric neurons. Depletion of MMϕ before weaning disrupts this process and results in abnormal intestinal transit. After weaning, MMϕ continue to interact closely with the ENS and acquire a neurosupportive phenotype. The latter is instructed by transforming growth factor-β produced by the ENS; depletion of the ENS and disruption of transforming growth factor-β signalling result in a decrease in neuron-associated MMϕ associated with loss of enteric neurons and altered intestinal transit. These findings introduce a new reciprocal cell-cell communication responsible for maintenance of the ENS and indicate that the ENS, similarly to the brain, is shaped and maintained by a dedicated population of resident macrophages that adapts its phenotype and transcriptome to the timely needs of the ENS niche.