Establishment and evaluation of an experimental rat model for high-altitude intestinal barrier injury

Luo, Han; Zhou, Daijun; Chen, Zhang; Zhou, Qian; Wu, Kui; Tian, Kangkai; Li, Zhiwei; Xiao, Zhifeng

doi:10.3892/etm.2016.4012

Cited by 17 publications

(8 citation statements)

References 33 publications

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“…(2017) who reported significant elevations in circulating endotoxins following exercise in normobaric hypoxia (14%

{F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}

), but not normoxia. Our data also confirm the findings of previous investigations demonstrating increased bacterial translocation following hypoxic exposures in rodent models (Luo et al., 2017; Q.‐Q. Zhou et al., 2011).…”

Section: Discussionsupporting

confidence: 92%

Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress

McKenna

Fennel

Berkemeier

et al. 2022

Experimental Physiology

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New Findings What is the central question of this study?What is the effect of hypobaric hypoxia on markers of exercise‐induced intestinal injury and symptoms of gastrointestinal (GI) distress? What is the main finding and its importance?Exercise performed at 4300 m of simulated altitude increased intestinal fatty acid binding protein (I‐FABP), claudin‐3 (CLDN‐3) and lipopolysaccharide binding protein (LBP), which together suggest that exercise‐induced intestinal injury may be aggravated by concurrent hypoxic exposure. Increases in I‐FABP, LBP and CLDN‐3 were correlated to exercise‐induced GI symptoms, providing some evidence of a link between intestinal barrier injury and symptoms of GI distress. Abstract We sought to determine the effect of exercise in hypobaric hypoxia on markers of intestinal injury and gastrointestinal (GI) symptoms. Using a randomized and counterbalanced design, nine males completed two experimental trials: one at local altitude of 1585 m (NORM) and one at 4300 m of simulated hypobaric hypoxia (HYP). Participants performed 60 min of cycling at a workload that elicited 65% of their NORM trueV̇normalO2max${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$. GI symptoms were assessed before and every 15 min during exercise. Pre‐ and post‐exercise blood samples were assessed for intestinal fatty acid binding protein (I‐FABP), claudin‐3 (CLDN‐3) and lipopolysaccharide binding protein (LBP). All participants reported at least one GI symptom in HYP compared to just one participant in NORM. I‐FABP significantly increased from pre‐ to post‐exercise in HYP (708 ± 191 to 1215 ± 518 pg ml−1; P = 0.011, d = 1.10) but not NORM (759 ± 224 to 828 ± 288 pg ml−1; P > 0.99, d = 0.27). CLDN‐3 significantly increased from pre‐ to post‐exercise in HYP (13.8 ± 0.9 to 15.3 ± 1.2 ng ml−1; P = 0.003, d = 1.19) but not NORM (13.7 ± 1.8 to 14.2 ± 1.6 ng ml−1; P = 0.435, d = 0.45). LBP significantly increased from pre‐ to post‐exercise in HYP (10.8 ± 1.2 to 13.9 ± 2.8 μg ml−1; P = 0.006, d = 1.12) but not NORM (11.3 ± 1.1 to 11.7 ± 0.9 μg ml−1; P > 0.99, d = 0.32). I‐FABP (d = 0.85), CLDN‐3 (d = 0.95) and LBP (d = 0.69) were all significantly higher post‐exercise in HYP compared to NORM (P ≤ 0.05). Overall GI discomfort was significantly correlated to ΔI‐FABP (r = 0.71), ΔCLDN‐3 (r = 0.70) and ΔLBP (r = 0.86). These data indicate that cycling exercise performed in hypobaric hypoxia can cause intestinal injury, which might cause some commonly reported GI symptoms.

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“…(2017) who reported significant elevations in circulating endotoxins following exercise in normobaric hypoxia (14%

{F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}

Section: Discussionsupporting

confidence: 92%

Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress

McKenna

Fennel

Berkemeier

et al. 2022

Experimental Physiology

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“…While the risk of GI complications such as GI bleeding with ibuprofen use has been reported to be relatively low (32), this risk may be exacerbated by other contributing factors in the context of high-altitude. For example, rodent models have demonstrated that hypoxia alone can damage intestinal cells and increase intestinal permeability (33,34). While not assessed in the present study, the compounding effects of ibuprofen and hypoxia on intestinal barrier injury is an interesting area of study that may be relevant for high-altitude travel.…”

Section: Discussionmentioning

confidence: 99%

Ibuprofen Increases Markers of Intestinal Barrier Injury But Suppresses Inflammation at Rest and After Exercise in Hypoxia

McKenna

Ducharme

Berkemeier

et al. 2022

Medicine &Amp; Science in Sports &Amp; Exercise

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Purpose: The purpose of this study was to evaluate the effects of acute ibuprofen consumption (2 Â 600-mg doses) on markers of enterocyte injury, intestinal barrier dysfunction, inflammation, and symptoms of gastrointestinal (GI) distress at rest and after exercise in hypobaric hypoxia. Methods: Using a randomized double-blind placebo-controlled crossover design, nine men (age, 28 ± 3 yr; weight, 75.4 ± 10.5 kg; height, 175 ± 7 cm; body fat, 12.9% ± 5%; VO 2 peak at 440 torr, 3.11 ± 0.65 L•min −1 ) completed a total of three visits including baseline testing and two experimental trials (placebo and ibuprofen) in a hypobaric chamber simulating an altitude of 4300 m. Preexercise and postexercise blood samples were assayed for intestinal fatty acid binding protein (I-FABP), ileal bile acid binding protein, soluble cluster of differentiation 14, lipopolysaccharide binding protein, monocyte chemoattractant protein-1, tumor necrosis factor α (TNF-α), interleukin-1β, and interleukin-10. Intestinal permeability was assessed using a dual sugar absorption test (urine lactulose-to-rhamnose ratio). Results: Resting I-FABP (906 ± 395 vs 1168 ± 581 pg•mL −1 ; P = 0.008) and soluble cluster of differentiation 14 (1512 ± 297 vs 1642 ± 313 ng•mL −1 ; P = 0.014) were elevated in the ibuprofen trial. Likewise, the urine lactulose-to-rhamnose ratio (0.217 vs 0.295; P = 0.047) and the preexercise to postexercise change in I-FABP (277 ± 308 vs 498 ± 479 pg•mL −1 ; P = 0.021) were greater in the ibuprofen trial. Participants also reported greater upper GI symptoms in the ibuprofen trial (P = 0.031). However, monocyte chemoattractant protein-1 (P = 0.007) and TNF-α (P = 0.047) were lower throughout the ibuprofen trial compared with placebo (main effect of condition). Conclusions: These data demonstrate that acute ibuprofen ingestion aggravates markers of enterocyte injury and intestinal barrier dysfunction at rest and after exercise in hypoxia. However, ibuprofen seems to suppress circulating markers of inflammation.

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“…These changes can lead to mucosal barrier dysfunction. In addition, hypoxia can affect the intestinal mucosal immune system [49]. Low temperature can also affect the gut microbiome, which has a protective effect on obesity [50].…”

Section: Discussionmentioning

confidence: 99%

Succession of the Gut Microbiome in the Tibetan Population of the Minjiang River Basin

Sun

et al. 2021

Preprint

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Background: Tibetans are one of the oldest ethnic groups in China and South Asia. Tibetans have a unique lifestyle and a long history, which leads to the particularity of the composition and function of their gut microflora. Tibetans in the Minjiang River basin have gradually increased their migration to the Chengdu Plain in recent years. Based on the analysis of 1059 Tibetans in the Minjiang River basin at an altitude of 500-4001 m, we analyzed the characteristics of the gut microbiome and further elaborated the main factors affecting the succession of the gut microbiome in the Tibetan population.Results: Our study found that the dominant phyla of the Tibetan population were Bacteroidetes and Firmicutes, and the main genera were Prevotella and Bacteroides. To further study the factors affecting the gut microbial composition of the Tibetan population, 115 total parameters of 7 categories were evaluated. The results showed that altitude was the most important factor affecting the variation in the microbial community in the Tibetan population, and the change in altitude promoted the succession of the gut microbial community. In the process of migration from high altitudes to the plain, the gut microbial composition of late immigrants was similar to that of plateau aborigines, while that of early immigrants was similar to that of plain aborigines. Migration to Tibet is related to the loss of indigenous gut microbial community species. In addition, from low altitude to high altitude, the similarity of the microbial community with the high-altitude population increased with the reproduction of offspring after marriage. Changes in these microbials will affect the metabolism, disease incidence and cell function of the Tibetan population. The other two sets (AGP and Z208) of altitude data also showed the impact of altitude on the microbial community.Conclusions: This is the first large-scale study on the factors influencing the gut microflora in a Tibetan population. Our study confirmed that altitude change is the most important factor affecting the distribution of the microflora in the Tibetan population and provided abundant and unique data to explore the interaction of impact parameter-gut microbiome-host function and disease.

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Establishment and evaluation of an experimental rat model for high-altitude intestinal barrier injury

Cited by 17 publications

References 33 publications

Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress

Exercise in hypobaric hypoxia increases markers of intestinal injury and symptoms of gastrointestinal distress

Ibuprofen Increases Markers of Intestinal Barrier Injury But Suppresses Inflammation at Rest and After Exercise in Hypoxia

Succession of the Gut Microbiome in the Tibetan Population of the Minjiang River Basin

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