"a leaky gut may play a critical role in the development of age-related inflammation and frailty"

The quote heading this post is taken from the findings reported by Yanfei Qi and colleagues [1] who set out to investigate whether "an aging-associated leaky gut is linked to the age-related inflammation and frailty."

'Leaky gut' is still something of a contentious claim in medical and scientific circles despite some increasing evidence to say that it is a real phenomenon and potentially relevant to several conditions (see here) including some parts of the autism spectrum (see here). Although leaky gut is perhaps a slight misnomer - we all have leaky guts to some degree - the more accurate term 'intestinal hyperpermeability' suggests that for several different reasons, parts of the gastrointestinal (GI) tract may, at times or more chronically, be slightly more permeable that they typically should be. This in turn means that the contents of the GI tract - food derivatives, gut bacteria, etc - might be more readily exposed to parts of the body that they really shouldn't be and onward, potentially pathogenic.

Qi et al carried out some important analysis on two cohorts of differing ages (18-30 years old vs. 70 years and over) with regards to serum samples provided by participants. Markers of immune function, specifically inflammatory related compounds (e.g. tumour necrosis factor (TNF)-α and interleukin (IL)-6)) were assayed for, alongside levels of zonulin "a marker for leaky gut". Zonulin is something that I've covered quite recently on this blog in relation to autism research (see here). This biological data gathered by Qi and colleagues was also complemented by physiological measures such as "strength of plantar flexor muscles and number of steps taken per day."

Results: serum concentrations of zonulin were quite a bit - 22% - higher in the older participants compared to younger ones. Researchers also reported that levels of "high-mobility group box protein (HMGB1, a nuclear protein triggering inflammation)" were elevated in the older participants group too. They observed that zonulin levels also seemed to tie into concentrations of TNF-α and IL-6 (albeit not necessarily impressively). Zonulin levels also showed a potentially important *relationship* with "habitual physical activity" (those 'steps per day' data that was collected). The conclusion: "Serum zonulin was associated with both systemic inflammation and 2 key indices of physical frailty. These data suggest that a leaky gut may play a critical role in the development of age-related inflammation and frailty."

This is interesting stuff. It kinda accords with other independent data suggesting that generally speaking, gut barrier function does not necessarily have to deteriorate with age, but under certain circumstances such as age + inflammation, there might be effects to had [2]. Certain classes of medication might also show some involvement in this process too [3]. Although by no means a universal connection, I was interested in these results in the context of autism. Specifically how those Esnafoglu et al findings [4] reporting on 'significantly higher' serum zonulin levels in their cohort with autism, might also tie into reports of inflammatory markers being elevated in at least a subgroup of those on the autism spectrum (see here for example). I'd like to see the Qi study replicated with quite a few different labels and subgroups within labels...

In relation to the suggestion that serum zonulin levels negatively correlated with habitual physical activity (steps per day), again, there is a whole other research agenda to be [cautiously] followed. It's already known that certain patterns of exercise can affect (increase) intestinal permeability [5] although the specifics still require quite a bit more investigation (hint: exercising for 2 hours plus at a time is probably not great for gut function). As with everything in life, there is a balance to be struck between too little and too much of a good thing...

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[1] Qi Y. et al. Intestinal Permeability Biomarker Zonulin is Elevated in Healthy Aging. J Am Med Dir Assoc. 2017 Jul 1. pii: S1525-8610(17)30297-9.

[2] Valentini L. et al. Small intestinal permeability in older adults. Physiol Rep. 2014 Apr 22;2(4):e00281.

[3] Meier J. & Sturm A. The intestinal epithelial barrier: does it become impaired with age? Dig Dis. 2009;27(3):240-5.

[4] Esnafoglu E. et al. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects. J Pediatr. 2017 May 11. pii: S0022-3476(17)30487-0.

[5] Costa RJS. et al. Systematic review: exercise-induced gastrointestinal syndrome-implications for health and intestinal disease. Aliment Pharmacol Ther. 2017 Aug;46(3):246-265.

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