The intestine is responsible for absorption of nutrients but also to keep large molecules and germs out of our bodies. It has been suggested that exercise may result in a "leaky gut", a condition where this barrier function is compromised. This is also potentially a cause for gastro-intestinal (GI) problems we sometimes see in athletes. Let's explore.
The intestine plays an important role in absorption but also in the prevention of infection, chronic inflammation and other problems. The intestine is essentially a tube, lined by a single layer of cells, that form the barrier between the inside of the gut and the rest of the body. This barrier is effective at absorbing nutrients, but also prevents most large molecules and germs passing from inside the bowel into the bloodstream. In some circumstances, this barrier can become less effective and "leaky". Exercise may be one of those circumstances. Whether this is a problem and whether this is sometimes a cause of reported GI problems remains a topic of investigation. Here we will investigate whether a leaky gut (scientists call this increased permeability) may be caused by heat or by a lack of oxygen (hypoxia).
The intestine is essentially a barrier effective at absorbing nutrients, but also preventing most large molecules and germs passing from inside the bowel into the bloodstream. In some circumstances, this barrier can become less effective and "leaky".
What causes a leaky gut?
Exercise has an effect on the muscles, heart and lungs but also on the gut. Exercise, can, in some cases, result in GI-symptoms such as vomiting, diarrhoea or bloating (see blogs gastro-intestinal symptoms in athletes and causes of GI problems in athletes).
A considerable amount of research has investigated how exercise affects the gut, trying to discover the underlying mechanisms behind exercise-related gastro-intestinal or GI symptoms and intestinal permeability (see also blog causes of GI problems in athletes). Two of these mechanisms are:
a reduced splanchnic blood flow (a reduction in blood flow to the gut during exercise),
an increase in core temperature.
Increased muscular activity and metabolism during exercise generate heat, which results in an increase in core temperature. Normally maintained around 37°C, core temperature can rise during exercise to 40°C. In both laboratory and human studies, this rise in core temperature has been associated with increased permeability of cells within the GI tract. An increase in permeability means that otherwise impassable molecules and bacteria contained within the GI tract can now transit into circulating blood. If these molecules and bacteria cannot be cleared at a fast enough rate, endotoxemia can occur. This is a potentially life-threatening inflammatory response associated with pathological conditions such as heat exhaustion and heat stroke.
More heat, more permeability?
In a review article published in 2017, Pires and colleagues (1) highlighted a potential sliding scale relationship between intestinal permeability and core temperature. They explained that when core temperature reaches 38.5°C permeability is increased in some athletes. However, when core temperature reaches and goes above 39°C, increased GI permeability is universal.
However, exercise also causes a redistribution of blood flow away from the gut towards the working muscle, to aid in nutrient delivery and dissipate heat. This results in a reduction of the delivery of blood (and thus oxygen) to the gut. It is not yet clear which mechanism, heat or hypoxia, contributes most towards increased permeability of the GI tract. But we do know that they can both contribute.
Two new studies
Two recent, currently unpublished studies, aimed to investigate this relationship by heating (resting) participants in a warm bath set at 40°C for an hour. Therefore, a rise in core temperature was likely, with no or minimal reduction in GI blood flow. In one trial, core temperature was maintained at 38.5°C in the other trial between 39 - 39.5°C. A stable core temperature was achieved through raising and lowering the participants in and out of the bath.
Measuring permeability of the gut
To measure permeability, participants ingest a drink containing two or more sugars (often lactulose and rhamnose). One of these sugars is readily absorbed through the small intestinal wall, whilst the other, often lactulose, is not typically absorbed in the small intestine, so its appearance in later urine or plasma analysis is used as an indicator of small intestinal permeability.
A mild increase in the plasma ratio of the sugars was observed in all trials with no difference observed between conditions including, interestingly, the control condition whereby participants rested in a laboratory at 22°C. Whilst this could be mistaken as an indication of increased permeability, it is likely that the increase in plasma ratio represented the normal rate of digestion of the sugars across the GI tract. The participants also reported no appearance of GI symptoms, but instead reported symptoms also associated with heat illness, such as light headedness and nausea.
Can glutamine prevent a leaky gut?
This study was followed by a similar protocol but with some key differences. In this second study there was no control on core temperature and this time I-FABP was also measured as a marker of GI injury. I-FABP is a protein located within the tips of the lining of the small intestine that is quickly shed in response to disturbances to the GI tract. The researchers also supplemented participants with 0.5 g.kg body mass of glutamine two hours before being submerged in the bath. Glutamine has previously demonstrated attenuating effects on GI permeability (2) and core temperature (3), with a possibly small reducing effect on I-FABP. However, this had not been researched in resting human participants exposed to this type of heat stress. The results showed a slightly higher increase in plasma ratio of the sugars when compared to the previous study. Peak core temperature reached 39.19°C and 39.27°C in the placebo and glutamine trials, respectively. Both trials showed an increase in I-FABP, but glutamine supplementation showed no effect on any markers or symptoms.
Together, these studies suggest that hyperthermia likely plays a minor role in the development of a leaky gut
Hyperthermia seems to play a minor role in development of the leaky gut
Together, these studies suggest that hyperthermia likely plays a minor role in the development of a leaky gut. This leaves hypoxia (caused by a reduction in oxygen delivery to the gut) as the most likely factor underlying an increase in exercise-induced permeability.
Glutamine supplementation does not seem to have any effect.
Pires, W., Veneroso, C.E., Wanner, S.P., Pacheco, D.A.S., Vaz, G.C., Amorim, F.T., Tonoli, C., Soares, D.D. and Coimbra, C.C. (2017) Association Between Exercise-Induced Hyperthermia and Intestinal Permeability: A Systematic Review. Sports Medicine, 47 (7), 1389-1403.
Pugh, J.N., Sage, S., Hutson, M., Doran, D.A., Fleming, S.C., Highton, J., Morton, J.P. and Close, G.L. (2017) Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner. European Journal of Applied Physiology, 117 (12), 2569-2577.
Soares AD, Costa KA, Wanner SP, Santos RG, Fernandes SO, Martins FS, Nicoli JR, Coimbra CC, Cardoso VN. Dietary glutamine prevents the loss of intestinal barrier function and attenuates the increase in core body temperature induced by acute heat exposure. Br J Nutr. 2014 Nov 28;112(10):1601-10.