scholarly journals A glucose-supplemented diet enhances gut barrier integrity in Drosophila

Biology Open ◽  
2021 ◽  
pp. bio.056515
Author(s):  
Anthony Galenza ◽  
Edan Foley
Keyword(s):  
Dietary Intervention ◽  
Caloric Intake ◽  
Intestinal Barrier ◽  
Lifespan Extension ◽  
Gut Barrier ◽  
Barrier Integrity ◽  
Preventative Measures ◽  
Insulin Activity ◽  
Underlying Mechanisms ◽  
Effects Of Aging

Dietary intervention has received considerable attention as an approach to extend lifespan and improve aging. However, questions remain regarding optimal dietary regimes and underlying mechanisms of lifespan extension. Here, we asked how an increase of glucose in a chemically defined diet extends the lifespan of adult Drosophila. We showed that glucose-dependent lifespan extension is not a result of diminished caloric intake, or changes to systemic insulin activity, two commonly studied mechanisms of lifespan extension. Instead, we found that flies raised on glucose-supplemented food increased the expression of cell adhesion genes, delaying age-dependent loss of intestinal barrier integrity. Furthermore, we showed that chemical disruption of the gut barrier negated the lifespan extension associated with glucose-treatment, suggesting that glucose-supplemented food prolongs adult viability by enhancing the intestinal barrier. We believe our data contribute to understanding intestinal homeostasis, and may assist efforts to develop preventative measures that limit effects of aging on health.

scholarly journals Glucose extends lifespan through enhanced intestinal barrier integrity in Drosophila

2020 ◽  
Author(s):  
Anthony Galenza ◽  
Edan Foley
Keyword(s):  
Dietary Intervention ◽  
Intestinal Barrier ◽  
Underlying Mechanism ◽  
Cell Junction ◽  
Lifespan Extension ◽  
Barrier Integrity ◽  
Preventative Measures ◽  
Insulin Activity ◽  
Intestinal Barrier Integrity ◽  
Effects Of Aging

SUMMARYDietary intervention has received considerable attention as an approach to extend lifespan and improve aging. However, questions remain regarding optimal dietary regime and underlying mechanism of lifespan extension. Here, we asked how glucose-enriched food extends the lifespan of Drosophila. We showed that glucose-dependent lifespan extension is independent of caloric restriction, or insulin activity, two established mechanisms of lifespan extension. Instead, we found that flies raised on glucose-enriched food increased the expression of cell junction proteins, and extended intestinal barrier integrity with age. Furthermore, chemical disruption of the intestinal barrier removed the lifespan extension associated with glucose-treatment, suggesting that glucose-enriched food prolongs adult viability by enhancing the intestinal barrier. We believe our data contribute to our understanding of intestinal health and may help efforts to develop preventative measures to limit the effects of aging and disease.

scholarly journals 2’-fucosyllactose (2’-FL) Supplementation Improves Gut Barrier Function and Lipid Metabolism in HF-fed Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 425-425
Author(s):  
Sunhye Lee ◽  
Michael Goodson ◽  
Wendie Vang ◽  
Karen Kalanetra ◽  
Daniela Barile ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gut Barrier ◽  
Low Fat ◽  
Barrier Integrity ◽  
Gut Barrier Function

Abstract Objectives 2’-fucosyllactose (2’-FL), the most predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. The aim of this study was to determine the beneficial effect of 2’-FL on intestinal barrier integrity and metabolic functions in low-fat (LF)- and high-fat (HF)-fed mice. Methods Male C57/BL6 mice (n = 32, 8/group; 6 weeks old, JAX, CA) were counter-balanced into four weight-matched groups and fed either a low-fat (LF; 10% kcal fat with 7% kcal sucrose) or HF (45% kcal fat with 17% kcal sucrose) with or without supplementation of 2’-FL in the diet [10% (w/w), 8 weeks; LF/2’-FL or HF/2’-FL; BASF, Germany]. General phenotypes (body weight, energy intake, fat and lean mass), intestinal permeability (ex vivo in Ussing chambers), lipid profiles, and microbial metabolites were assessed. Results 2’-FL significantly attenuated the HF-induced increase in body fat mass with a trend to decrease body weight gain. 2’-FL significantly decreased intestinal permeability in LF-fed mice with a trend for a decrease in HF-fed mice. This was associated with a significant increase in interleukin-22, a cytokine known to have a protective role in intestinal barrier function. Visceral adipocyte size was significantly decreased by 2’-FL in both LF- and HF-fed mice. 2’-FL suppressed HF-induced upregulation of adipogenic transcription factors peroxisome proliferator-activated receptor gamma and sterol regulatory element binding protein-1c in the liver. Lastly, 2’-FL supplementation led to a significant elevation of lactic acid concentration in the cecum of HF-fed mice, which is known to be a product from beneficial microbes. Conclusions 2’-FL supplementation improved gut barrier integrity and lipid metabolism in mice with and without the metabolic challenge of HF feeding. These findings support the use of 2’-FL in the control of gut barrier function and metabolic homeostasis under normal and abnormal physiological conditions. Funding Sources BASF (Germany).

scholarly journals Andrographolide Exerts Antihyperglycemic Effect through Strengthening Intestinal Barrier Function and Increasing Microbial Composition of Akkermansia muciniphila

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Hongming Su ◽  
Jianling Mo ◽  
Jingdan Ni ◽  
Huihui Ke ◽  
Tao Bao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Glutathione Depletion ◽  
Intestinal Barrier Function ◽  
Microbiota Composition ◽  
Gut Barrier ◽  
Barrier Integrity ◽  
Akkermansia Muciniphila ◽  
Microbial Species ◽  
Junction Protein

Accumulating evidence indicates that type 2 diabetes (T2D) is associated with intestinal barrier dysfunction and dysbiosis, implying the potential targets for T2D therapeutics. Andrographolide was reported to have several beneficial effects on diabetes and its associated complications. However, the protective role of andrographolide, as well as its underlying mechanism against T2D, remains elusive. Herein, we reported that andrographolide enhanced intestinal barrier integrity in LPS-induced Caco-2 cells as indicated by the improvement of cell monolayer barrier permeability and upregulation of tight junction protein expression. In addition, andrographolide alleviated LPS-induced oxidative stress by preventing ROS and superoxide anion radical overproduction and reversing glutathione depletion. In line with the in vitro results, andrographolide reduced metabolic endotoxemia and strengthened gut barrier integrity in db/db diabetic mice. We also found that andrographolide appeared to ameliorate glucose intolerance and insulin resistance and attenuated diabetes-associated redox disturbance and inflammation. Furthermore, our results indicated that andrographolide modified gut microbiota composition as indicated by elevated Bacteroidetes/Firmicutes ratio, enriched microbial species of Akkermansia muciniphila, and increased SCFAs level. Taken together, this study demonstrated that andrographolide exerted a glucose-lowering effect through strengthening intestinal barrier function and increasing the microbial species of A. muciniphila, which illuminates a plausible approach to prevent T2D by regulating gut barrier integrity and shaping intestinal microbiota composition.

scholarly journals Keep calm: the intestinal barrier at the interface of peace and war

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Lester Thoo ◽  
Mario Noti ◽  
Philippe Krebs
Keyword(s):  
Inflammatory Diseases ◽  
Pathological Condition ◽  
Treatment Strategies ◽  
Intestinal Barrier ◽  
Cell Types ◽  
Epithelial Barrier ◽  
Barrier Integrity ◽  
Epithelial Barriers ◽  
Underlying Mechanisms ◽  
And Function

Abstract Epithelial barriers have to constantly cope with both harmless and harmful stimuli. The epithelial barrier therefore serves as a dynamic and not static wall to safeguard its proper physiological function while ensuring protection. This is achieved through multiple defence mechanisms involving various cell types - epithelial and non-epithelial - that work in an integrated manner to build protective barriers at mucosal sites. Damage may nevertheless occur, due to pathogens, physical insults or dysregulated immune responses, which trigger a physiologic acute or a pathologic chronic inflammatory cascade. Inflammation is often viewed as a pathological condition, particularly due to the increasing prevalence of chronic inflammatory (intestinal) diseases. However, inflammation is also necessary for wound healing. The aetiology of chronic inflammatory diseases is incompletely understood and identification of the underlying mechanisms would reveal additional therapeutic approaches. Resolution is an active host response to end ongoing inflammation but its relevance is under-appreciated. Currently, most therapies aim at dampening inflammation at damaged mucosal sites, yet these approaches do not efficiently shut down the inflammation process nor repair the epithelial barrier. Therefore, future treatment strategies should also promote the resolution phase. Yet, the task of repairing the barrier can be an arduous endeavour considering its multiple integrated layers of defence - which is advantageous for damage prevention but becomes challenging to repair at multiple levels. In this review, using the intestines as a model epithelial organ and barrier paradigm, we describe the consequences of chronic inflammation and highlight the importance of the mucosae to engage resolving processes to restore epithelial barrier integrity and function. We further discuss the contribution of pre-mRNA alternative splicing to barrier integrity and intestinal homeostasis. Following discussions on current open questions and challenges, we propose a model in which resolution of inflammation represents a key mechanism for the restoration of epithelial integrity and function.

Bacterial Translocation from the Gut to the Distant Organs: An Overview

2017 ◽  
Vol 71 (Suppl. 1) ◽  
pp. 11-16 ◽  
Author(s):  
Ravinder Nagpal ◽  
Hariom Yadav
Keyword(s):  
Bacterial Translocation ◽  
Inflammatory Responses ◽  
Close Association ◽  
Intestinal Barrier ◽  
Research Field ◽  
Gut Health ◽  
Gut Barrier ◽  
Barrier Integrity ◽  
Gut Microbes ◽  
Basolateral Side

Background: The intestinal epithelial layer is the chief barricade between the luminal contents and the host. A healthy homeostatic intestinal barrier is pivotal for maintaining gastrointestinal health, which impacts the overall health as it safeguards the gut-blood axis and checks gut microbes including potential pathogens from entering into the circulation. Summary: Under healthy milieus, the intestinal barrier is generally very dynamic and effective, with luminal side being heavily infested with a wide variety of gut microbes while the basolateral side remains virtually sterile. However, certain conditions such as abnormal exposure to toxins, drugs, pathogens etc. or a state of hyper-inflammation due to disease conditions may weaken or destabilize the integrity of gut epithelia. A perturbed gut integrity and permeability (“leaky gut”) may lead to microbial (bacterial) translocation, and the eventual leakage of bacteria or their metabolites into the circulation can make the host susceptible to various types of diseases via inducing chronic or acute inflammatory response. Key Message: Given a close association with gut integrity, bacterial translocation and inflammatory responses have recently emerged as a clinically important research field and have unveiled novel aspects of gut microbial ecology and various gastrointestinal, metabolic, and lifestyle diseases. This review aims to describe the significance of a healthy gut barrier integrity and permeability, as well as the factors and consequences associated with a compromised gut barrier, while discussing briefly the dietary approaches including probiotics and prebiotics that could ameliorate gut health by restoring gut environment and barrier integrity, thereby preventing bacterial translocation.

scholarly journals Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Leila B. Giron ◽  
Harsh Dweep ◽  
Xiangfan Yin ◽  
Han Wang ◽  
Mohammad Damra ◽  
...  
Keyword(s):  
Systemic Inflammation ◽  
Intestinal Barrier ◽  
Microbial Translocation ◽  
Gut Permeability ◽  
Gut Barrier ◽  
Potential Force ◽  
Barrier Integrity ◽  
Plasma Metabolome ◽  
Tight Junction Permeability ◽  
Plasma Markers

A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.

scholarly journals Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner

GeroScience ◽  
2021 ◽  
Author(s):  
Yoko O. Henderson ◽  
Nazmin Bithi ◽  
Christopher Link ◽  
Jie Yang ◽  
Rebecca Schugar ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Dietary Intervention ◽  
Caloric Intake ◽  
Production Capacity ◽  
Late Life ◽  
Model Organisms ◽  
Intermittent Fasting ◽  
Sexually Dimorphic ◽  
Average Life Expectancy ◽  
Multiple Components

AbstractGlobal average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan. However, DR is not widely implemented in the clinic due to patient compliance and its lack of mechanistic underpinnings. Thus, the present study tested the effects of a somewhat more clinically applicable and adoptable DR regimen, every-other-day (EOD) intermittent fasting, on frailty in 20-month-old male and female C57BL/6 mice. Frailty was determined by a series of metabolic, musculoskeletal, and cognitive tasks performed prior to and toward the end of the 2.5-month dietary intervention. Late-life EOD fasting attenuated overall energy intake, hypothalamic inflammatory gene expression, and frailty in males. However, it failed to reduce overall caloric intake and had a little positive effect in females. Given that the selected benefits of DR are dependent on augmented production of the gasotransmitter hydrogen sulfide (H2S) and that renal H2S production declines with age, we tested the effects of EOD fasting on renal H2S production capacity and its connection to frailty in males. EOD fasting boosted renal H2S production, which positively correlated with improvements in multiple components of frailty tasks. Therefore, late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the effects of late-life EOD fasting on frailty.

scholarly journals Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity

Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1946368
Author(s):  
Angélica Cruz-Lebrón ◽  
Ramona Johnson ◽  
Claire Mazahery ◽  
Zach Troyer ◽  
Samira Joussef-Piña ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Opioid Use ◽  
Barrier Integrity ◽  
Intestinal Barrier Integrity ◽  
Chronic Opioid Use

scholarly journals Differences in Intestinal Barrier Development between Intrauterine Growth Restricted and Normal Birth Weight Piglets

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 990 ◽  
Author(s):  
Jarosław Olszewski ◽  
Romuald Zabielski ◽  
Tomasz Skrzypek ◽  
Piotr Matyba ◽  
Małgorzata Wierzbicka ◽  
...  
Keyword(s):  
Intestinal Barrier ◽  
Goblet Cells ◽  
Normal Birth Weight ◽  
Intestinal Function ◽  
Gut Barrier ◽  
Intrauterine Growth ◽  
Normal Birth ◽  
Gut Mucosa ◽  
Average Size ◽  
Distal Jejunum

Intrauterine growth restricted (IUGR) piglets are born at term but have low birth mass and a characteristic shape of the head. Impaired general condition, especially in intestinal function, leads to an increase in the occurrence of diarrhoea and high mortality in the first days of life. So far, the mechanical and immunological gut barrier functions in IUGR are poorly understood. The aim of this study was to microscopically evaluate the early postnatal changes in the gut mucosa occurring in IUGR piglets. Whole-tissue small intestine samples were collected from littermate pairs (IUGR and normal) on postnatal day (PD) 7, 14 and 180 and analysed by light microscopy. We found that in the IUGR piglets, the percentage of intraepithelial leukocytes was reduced in the duodenum on PD 7, but it increased in the proximal and middle jejunum both on PD 7 and PD 14, which suggested the development of an inflammatory process. The number of goblet cells was also reduced on PD 14. The average size of the Peyer’s patches in the distal jejunum and ileum showed significant reduction on PD 7 as compared to normal pigs; however, on PD 14, it returned to normal. On PD 180, we did not find any differences in the measured parameters between the IUGR and the normal pigs. In conclusion, we found that in one-week-old IUGR pig neonates, the gut barrier and the immune system structures display signs of retarded development but recover within the second postnatal week of life.

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