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1.
Review of paediatric gastrointestinal physiology relevant to the absorption of orally administered medicines.
Wollmer, E, Ungell, AL, Nicolas, JM, Klein, S
Advanced drug delivery reviews. 2022;:114084
Abstract
Despite much progress in regulations to improve paediatric drug development, there remains a significant need to develop better medications for children. For the design of oral dosage forms, a detailed understanding of the specific gastrointestinal (GI) conditions in children of different age categories and how they differ from GI conditions in adults is essential. Several review articles have been published addressing the ontogeny of GI characteristics, including luminal conditions in the GI tract of children. However, the data reported in most of these reviews are of limited quality because (1) information was cited from very old publications and sometimes low quality sources, (2) data gaps in the original data were filled with textbook knowledge, (3) data obtained on healthy and sick children were mixed, (4) average data obtained on groups of patients were mixed with data obtained on individual patients, and (5) results obtained using investigative techniques that may have altered the outcome of the respective studies were considered. Consequently, many of these reviews draw conclusions that may be incorrect. The aim of the present review was to provide a comprehensive and updated overview of the available original data on the ontogeny of GI luminal conditions relevant to oral drug absorption in the paediatric population. To this end, the PubMed and Web of Science metadatabases were searched for appropriate studies that examined age-related conditions in the oral cavity, esophagus, stomach, small intestine, and colon. Maturation was observed for several GI parameters, and corresponding data sets were identified for each paediatric age group. However, it also became clear that the ontogeny of several GI traits in the paediatric population is not yet known. The review article provides a robust and valuable data set for the development of paediatric in vitro and in silico biopharmaceutical tools to support the development of age-appropriate dosage forms. In addition, it provides important information on existing data gaps and should provide impetus for further systematic and well-designed in vivo studies on GI physiology in children of specific age groups in order to close existing knowledge gaps and to sustainably improve oral drug therapy in children.
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2.
THE EFFECT OF ENTERAL LACTOFERRIN SUPPLEMENTATION IN PREVENTION OF MORBIDITY ASSOCIATED WITH IMMATURE DIGESTIVE TRACT IN PREMATURE INFANTS: PROSPECTIVE COHORT STUDY.
Dobryk, D, Dobryk, O, Dobryanskyy, D
Georgian medical news. 2022;(323):94-101
Abstract
Premature infants are at high risk for diseases associated with impaired adaptation of the immature digestive tract, such as necrotizing enterocolitis (NEC) or late-onset sepsis (LOS), as well as severe neonatal morbidities associated with these diseases. This study was aimed to evaluate the effectiveness of prophylactic enteral use of bovine lactoferrin for the prevention of severe neonatal diseases in premature infants. The prospective cohort study included 117 premature infants with gestational age (GA) of ≤32 weeks, a birth weight of ≤1,500 g, and an age of ≤72 hours. 27 infants who were receiving enteral feeds were randomized to receive lactoferrin at a dose of 100 mg/day until postmenstrual age (PMA) of 36 weeks or discharge (at least 4 weeks). 90 infants formed the control group and received standard treatment. The primary outcome was the incidence of LOS, the secondary outcomes were the incidence of necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), severe brain damage, bronchopulmonary dysplasia (BPD), overall mortality, as well as the age of achieving full enteral feeds, duration of antibacterial therapy, length of stay in NICU and the total length of hospital stay. Enteral lactoferrin supplementation did not reduce the incidence of LOS (29.6% in the lactoferrin group against 22.7% in the control group; p=0.85), NEC (5.6% vs. 1.8%, respectively; p=0.11) and overall mortality (18.5% vs. 9.1%, respectively; p=0.06), as well as the incidence of severe intraventricular hemorrhages (18.5% vs. 9.8%, respectively; p=0.17), PVL (11.1% vs. 2.2%, respectively; p=0.17) and BPD (14.8% vs. 25.6%, respectively; p = 0.25). Infants receiving lactoferrin were achieving full enteral feeds significantly faster compared to the control group (14 (10-17) days vs. 19 (13-32) days, respectively; p=0.007). The total length of hospital stay of infants with GA ≤28 weeks in the lactoferrin group was significantly shorter compared to the control group (74 (68-89) vs. 98 (83-109) days, respectively; p=0.048). Enteral lactoferrin supplementation at a dose of 100 mg/day does not affect the main morbidity and mortality of prematurely born infants with GA ≤ 32 weeks but may facilitate significantly faster achievement of the full enteral feeds and the reduction of the length of hospital stay in the tiniest infants.
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3.
Shaping the gut microbiota by bioactive phytochemicals: An emerging approach for the prevention and treatment of human diseases.
Sudheer, S, Gangwar, P, Usmani, Z, Sharma, M, Sharma, VK, Sana, SS, Almeida, F, Dubey, NK, Singh, DP, Dilbaghi, N, et al
Biochimie. 2022;:38-63
Abstract
The human digestive tract is the cottage to trillions of live microorganisms, which regulate health and illness. A healthy Gut Microbiota (GM) is necessary for preventing microbial growth, body growth, obesity, cancer, diabetes, and enhancing immunity. The equilibrium in GM's composition and the presence/absence of critical species enable specific responses to be essential for the host's better health condition. Research evidences revealed that the dietary plants and their bioactive phytochemicals (BPs) play an extensive and critical role in shaping the GM to get beneficial health effects. BPs are also known to improve gastrointestinal health and reduce the risk of several diseases by modulating GM-mediated cellular and molecular processes. Regular intake of BPs-rich vegetables, fruits, and herbal preparations promotes probiotic bacteria, including Bifidobacteria and Lactobacillus species, while inhibiting unwanted gut residents' development Escherichia coli, and Salmonella typhimurium etc. Upon consumption, BPs contact the GM that gets transformed before being absorbed from the gastrointestinal tract. Biotransformation of BPs by GM is linked with the enhancement of bioactivity/toxicity diminishment of the BPs compared to parental phytochemicals. Therefore, the current review focuses on the role of BPs in shaping GM for the prevention and treatment of human diseases.
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4.
Phenylethyl Isothiocyanate: A Bioactive Agent for Gastrointestinal Health.
Coscueta, ER, Sousa, AS, Reis, CA, Pintado, MM
Molecules (Basel, Switzerland). 2022;(3)
Abstract
The incidence of gastrointestinal pathologies (cancer in particular) has increased progressively, with considerable morbidity and mortality, and a high economic impact on the healthcare system. The dietary intake of natural phytochemicals with certain bioactive properties has shown therapeutic and preventive effects on these pathologies. This includes the cruciferous vegetable derivative phenylethyl isothiocyanate (PEITC), a bioactive compound present in some vegetables, such as watercress. Notably, PEITC has antioxidant, anti-inflammatory, bactericidal, and anticarcinogenic properties. This review summarized the current knowledge on the role of PEITC as a potential natural nutraceutical or an adjuvant against oxidative/inflammatory-related disorders in the gastrointestinal tract. We also discussed the safe and recommended dose of PEITC. In addition, we established a framework to guide the research and development of sustainable methodologies for obtaining and stabilizing this natural molecule for industrial use. With PEITC, there is great potential to develop a viable strategy for preventing cancer and other associated diseases of the gastrointestinal tract. However, this topic still needs more scientific studies to help develop new PEITC products for the nutraceutical, pharmaceutical, or food industries.
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5.
Pre-operative iron increases haemoglobin concentration before abdominal surgery: a systematic review and meta-analysis of randomized controlled trials.
Meyer, J, Cirocchi, R, Di Saverio, S, Ris, F, Wheeler, J, Davies, RJ
Scientific reports. 2022;(1):2158
Abstract
Professional surgical societies recommend the identification and treatment of pre-operative anaemia in patients scheduled for abdominal surgery. Our aim was to determine if pre-operative iron allows correction of haemoglobin concentration and decreased incidence of peri-operative blood transfusion in patients undergoing major abdominal surgery. MEDLINE, Embase and CENTRAL were searched for RCTs written in English and assessing the effect of pre-operative iron on the incidence of peri-operative allogeneic blood transfusion in patients undergoing major abdominal surgery. Pooled relative risk (RR), risk difference (RD) and mean difference (MD) were obtained using models with random effects. Heterogeneity was assessed using the Q-test and quantified using the I2 value. Four RCTs were retained for analysis out of 285 eligible articles. MD in haemoglobin concentration between patients with pre-operative iron and patients without pre-operative iron was of 0.81 g/dl (3 RCTs, 95% CI 0.30 to 1.33, I2: 60%, p = 0.002). Pre-operative iron did not lead to reduction in the incidence of peri-operative blood transfusion in terms of RD (4 RCTs, RD: - 0.13, 95% CI - 0.27 to 0.01, I2: 65%, p = 0.07) or RR (4 RCTs, RR: 0.57, 95% CI 0.30 to 1.09, I2: 64%, p = 0.09). To conclude, pre-operative iron significantly increases haemoglobin concentration by 0.81 g/dl before abdominal surgery but does not reduce the need for peri-operative blood transfusion. Important heterogeneity exists between existing RCTs in terms of populations and interventions. Future trials should target patients suffering from iron-deficiency anaemia and assess the effect of intervention on anaemia-related complications.
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6.
Glucose and Fructose Hydrogel Enhances Running Performance, Exogenous Carbohydrate Oxidation, and Gastrointestinal Tolerance.
Rowe, JT, King, RFGJ, King, AJ, Morrison, DJ, Preston, T, Wilson, OJ, O'Hara, JP
Medicine and science in sports and exercise. 2022;(1):129-140
Abstract
PURPOSE Beneficial effects of carbohydrate (CHO) ingestion on exogenous CHO oxidation and endurance performance require a well-functioning gastrointestinal (GI) tract. However, GI complaints are common during endurance running. This study investigated the effect of a CHO solution-containing sodium alginate and pectin (hydrogel) on endurance running performance, exogenous and endogenous CHO oxidation, and GI symptoms. METHODS Eleven trained male runners, using a randomized, double-blind design, completed three 120-min steady-state runs at 68% V˙O2max, followed by a 5-km time-trial. Participants ingested 90 g·h-1 of 2:1 glucose-fructose (13C enriched) as a CHO hydrogel, a standard CHO solution (nonhydrogel), or a CHO-free placebo during the 120 min. Fat oxidation, total and exogenous CHO oxidation, plasma glucose oxidation, and endogenous glucose oxidation from liver and muscle glycogen were calculated using indirect calorimetry and isotope ratio mass spectrometry. GI symptoms were recorded throughout the trial. RESULTS Time-trial performance was 7.6% and 5.6% faster after hydrogel ([min:s] 19:29 ± 2:24, P < 0.001) and nonhydrogel (19:54 ± 2:23, P = 0.002), respectively, versus placebo (21:05 ± 2:34). Time-trial performance after hydrogel was 2.1% faster (P = 0.033) than nonhydrogel. Absolute and relative exogenous CHO oxidation was greater with hydrogel (68.6 ± 10.8 g, 31.9% ± 2.7%; P = 0.01) versus nonhydrogel (63.4 ± 8.1 g, 29.3% ± 2.0%; P = 0.003). Absolute and relative endogenous CHO oxidation was lower in both CHO conditions compared with placebo (P < 0.001), with no difference between CHO conditions. Absolute and relative liver glucose oxidation and muscle glycogen oxidation were not different between CHO conditions. Total GI symptoms were not different between hydrogel and placebo, but GI symptoms were higher in nonhydrogel compared with placebo and hydrogel (P < 0.001). CONCLUSION The ingestion of glucose and fructose in hydrogel form during running benefited endurance performance, exogenous CHO oxidation, and GI symptoms compared with a standard CHO solution.
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7.
How Changes in the Nutritional Landscape Shape Gut Immunometabolism.
Tan, J, Ni, D, Ribeiro, RV, Pinget, GV, Macia, L
Nutrients. 2021;(3)
Abstract
Cell survival, proliferation and function are energy-demanding processes, fuelled by different metabolic pathways. Immune cells like any other cells will adapt their energy production to their function with specific metabolic pathways characteristic of resting, inflammatory or anti-inflammatory cells. This concept of immunometabolism is revolutionising the field of immunology, opening the gates for novel therapeutic approaches aimed at altering immune responses through immune metabolic manipulations. The first part of this review will give an extensive overview on the metabolic pathways used by immune cells. Diet is a major source of energy, providing substrates to fuel these different metabolic pathways. Protein, lipid and carbohydrate composition as well as food additives can thus shape the immune response particularly in the gut, the first immune point of contact with food antigens and gastrointestinal tract pathogens. How diet composition might affect gut immunometabolism and its impact on diseases will also be discussed. Finally, the food ingested by the host is also a source of energy for the micro-organisms inhabiting the gut lumen particularly in the colon. The by-products released through the processing of specific nutrients by gut bacteria also influence immune cell activity and differentiation. How bacterial metabolites influence gut immunometabolism will be covered in the third part of this review. This notion of immunometabolism and immune function is recent and a deeper understanding of how lifestyle might influence gut immunometabolism is key to prevent or treat diseases.
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8.
Gut-adipose tissue crosstalk: A bridge to novel therapeutic targets in metabolic syndrome?
Rosendo-Silva, D, Matafome, P
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021;(2):e13130
Abstract
The gut is one of the main endocrine organs in our body, producing hormones acknowledged to play determinant roles in controlling appetite, energy balance and glucose homeostasis. One of the targets of such hormones is the adipose tissue, a major energetic reservoir, which governs overall metabolism through the secretion of adipokines. Disturbances either in nutrient and metabolic sensing and consequent miscommunication between these organs constitute a key driver to the metabolic complications clustered in metabolic syndrome. Thus, it is essential to understand how the disruption of this crosstalk might trigger adipose tissue dysfunction, a strong characteristic of obesity and insulin resistance. The beneficial effects of metabolic surgery in the amelioration of glucose homeostasis and body weight reduction allowed to understand the potential of gut signals modulation as a treatment for metabolic syndrome-related obesity and type 2 diabetes. In this review, we cover the effects of gut hormones in the modulation of adipose tissue metabolic and endocrine functions, as well as their impact in tissue plasticity. Furthermore, we discuss how the modulation of gut secretome, either through surgical procedures or pharmacological approaches, might improve adipose tissue function in obesity and metabolic syndrome.
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9.
Awareness and Attitudes of Gut Health, Probiotics and Prebiotics in Australian Adults.
Khalesi PhD, S, Vandelanotte PhD, C, Thwaite BSc, T, Russell PhD, AMT, Dawson PhD, D, Williams PhD, SL
Journal of dietary supplements. 2021;(4):418-432
Abstract
The awareness of and attitudes toward gut health, probiotics, prebiotics and factors associated with probiotics use in Australian adults have been explored in a cross-sectional study using CQUniversity's National Social Survey (N = 1,265; 667 females). 58.9% of the participants were probiotics users, who were most commonly identified as female, younger, more educated (Ps < 0.05), with a higher awareness of gut health, and overall healthier lifestyle behaviors (fruits intake, activity, alcohol intake risk) compared to non-users. Maintaining health was the main reason for use. Many (59%) non-users reported a willingness to try probiotics, but only if recommended by a health professional. Probiotics use was associated with awareness of probiotic (odds ratio (OR): 2.02, p < 0.001) and prebiotic (OR:1.59, p = 0.003) terms, natural source of probiotics (OR:2.38, p < 0.001), recommended fruit serves (OR:1.32, p = 0.001), and alcohol score (OR:0.95, p = 0.036). Overall, those who had a healthier lifestyle and better understanding of gut health and probiotics were more likely to use probiotics. Education on gut health and probiotics from health professionals may improve probiotic use, especially in populations that are likely to benefit the most, including those with a specific condition or poor lifestyle.
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10.
The Microbiota and the Gut-Brain Axis in Controlling Food Intake and Energy Homeostasis.
Romaní-Pérez, M, Bullich-Vilarrubias, C, López-Almela, I, Liébana-García, R, Olivares, M, Sanz, Y
International journal of molecular sciences. 2021;(11)
Abstract
Obesity currently represents a major societal and health challenge worldwide. Its prevalence has reached epidemic proportions and trends continue to rise, reflecting the need for more effective preventive measures. Hypothalamic circuits that control energy homeostasis in response to food intake are interesting targets for body-weight management, for example, through interventions that reinforce the gut-to-brain nutrient signalling, whose malfunction contributes to obesity. Gut microbiota-diet interactions might interfere in nutrient sensing and signalling from the gut to the brain, where the information is processed to control energy homeostasis. This gut microbiota-brain crosstalk is mediated by metabolites, mainly short chain fatty acids, secondary bile acids or amino acids-derived metabolites and subcellular bacterial components. These activate gut-endocrine and/or neural-mediated pathways or pass to systemic circulation and then reach the brain. Feeding time and dietary composition are the main drivers of the gut microbiota structure and function. Therefore, aberrant feeding patterns or unhealthy diets might alter gut microbiota-diet interactions and modify nutrient availability and/or microbial ligands transmitting information from the gut to the brain in response to food intake, thus impairing energy homeostasis. Herein, we update the scientific evidence supporting that gut microbiota is a source of novel dietary and non-dietary biological products that may beneficially regulate gut-to-brain communication and, thus, improve metabolic health. Additionally, we evaluate how the feeding time and dietary composition modulate the gut microbiota and, thereby, the intraluminal availability of these biological products with potential effects on energy homeostasis. The review also identifies knowledge gaps and the advances required to clinically apply microbiome-based strategies to improve the gut-brain axis function and, thus, combat obesity.