Use Glutamine to Heal the Gut and Hinder Your Gut Bacteria from Eating Away Your BCAA, Arginine and Other Aminos

Image 1: Don't do this at home. A pig with cannules that have been dug into its digestive tract to study chemical enzymatic and microbial actions (University of Illinois)

With terms like "the leaky gut syndrome" and the usual quick (and not so quick) fixes a la "solutions for a leaky gut" being all over the blogosphere, I suspect that I am not telling you anything new, when I say that there is reasonable scientific evidence that glutamine is good for your gut (nice alliteration, by the way ;-). That it is yet also "good" for the bacteria in your gut may be news to you. According to a recently published study by scientists from the Laboratory of Gastrointestinal Microbiology, at the Nanjing Agricultural University in Nanjing, China, dietary l-glutamine can exert direct regulatory effects on the amino acid utilization of your gut bacteria - specifically their uptake and use of l-arginine and related amino acids (Dai. 2012).

"Hey, you gut bug, leave my arginine alone!"

It has been known forever that l-glutamine is the most abundant amino acid in the body. It's sheer ubiquitousness and rapid turnover relfect its crucial role in whole body nutrient metabolism and health. While fitness and health enthusiasts have long been mislead to believe that glutamine would exert direct ergogenic effects (cf. Amino Acids for SuperHumans: Part IV - Glutamine), scientists and laymen alike are now zoning in on its protective effects on the integrity and function of the small intestine. In this context it has recently become clear that

... AA [amino acid] metabolism in the small intestine plays important roles in the regulation of whole-body AA homeostasis. [...] Recent studies suggest that bacteria in the small intestine are active in the metabolism of AA, especially lysine, threonine, arginine, glutamate and glutamine. The rapid utilization and metabolism of glutamine by small-intestinal bacteria supports the view that glutamine is a key regulator of the survival and growth of bacteria in the intestine through the regulation of the bacterial metabolism of nitrogenous compounds particularly AA.

The usage of glutamine by your gut bacteria is yet not the only physiologically significant interaction between dietary glutamine and the billions of microorganisms in your gastrointestinal tract. According to Dai et al. glutamine may also affect the utilization and metabolism of other amino acids by small-intestinal bacteria "and metabolism in small-intestinal bacteria, and thusly influence the "the production and profile of nitrogenous compounds in the lumen of small intestine and whole-body amino acid homeostasis."

Complex interactions with a simple solution? Ramp up your glutamine intake!?

As you can see in figure 1 the influence of dietary glutamine on the uptake of nitrogen amino acids by Streptococcus sp., Escherichia coli, Klebsiellasp. and a number of jejunal mixed bacteria or ileal mixed bacteria from the small intestine of pigs (as omnivores they have a very similar digestive tract as humans) was profound, yet dose depended and overall pretty complicated.

Figure 1: Change in utilization [nmol /( 10 cells 3h )] of amino acids from the l-arginine family by small intestinal bacteria subsequent to incubation with 0, 0.5, 1, 2 and 5 mmol/L l-glutamine (data adapted from Dai. 2012)

While the incubation of the bacteria with different amounts of l-glutamine lead to increases and decreases of amino acids from the l-arginine family (cf. figure 1), its addition to a medium with the three BCAAs, leucine, isoleucine and valine (cf. figure 2) led to dose-dependent decreases in all three branched-chain amino acids and may thusly explain why direct ergogenic effects of l-glutamine usually occur in the context of low protein diets, only.

Figure 2: Change in utilization [nmol /( 10 cells 3h )] of branched-chain amino acids by small intestinal bacteria subsequent to incubation with 0, 0.5, 1, 2 and 5 mmol/L l-glutamine (data adapted from Dai. 2012)

The addition of glutamine to low protein diets (and or low dose BCAA supplements) may simply facilitates that the small amount of BCAAs that is present in the die / supplement, will actually make it to the gut border and into your system (and is not "eaten by bacteria" before), where it (and leucine in particular) is then able to exert its mTOR-mediated protein synthetic effects.

Species, dosage and amino acid dependence - further investigations necessary

If you take a look at all the data from the Dai study, it is immediately evident that things are way more complicated than a cursory look at the graphs in figure 1-2 would suggest:

• the net effect on the metabolism of amino acids from the arginine-family is particularly pronounced; the production / conversion of arginine to ornithine and citrulline increased and the overall use of arginine by the bacteria decreased (in some cases profoundly) 
• the increased glutamate production from E. coli could be of particular importance, in view of the multi-faceted function of glutamate in the mammalian (and thusly human, as well) metabolism
• the decrease in the utlization of BCAAs, but also the amino acids from the serine aspartate family, i.e. l-alanine, l-asparagine, l-aspartate, glycine, l-serine and l-threonine allow for a greater uptake and utilization of these physiological important amino acids by the enterocytes

All these factors lead the scientists to conclude that high enough amounts of dietary or supplemental "glutamine [are] not only nutritionally important, but also crucial for maintaining gut health and function", because

• 

  Illustration 1: Potential gut microbiome mediated benefits of higher dietary or supplemental l-glutamine intake; maybe it's still worth taking although it's not a proven ergogenic

  they will fulfill the glutamine requirements of the potential pathogenic bacteria E. coli and Klebsiellasp. and thusly make up for their detrimental effect on the amino acid availability of the host
• the thusly well-nurished and healthy gut lining protects the host (you) from bacterial invasion and infection
• with their role in the intestinal signaling pathways, the increased availability of arginine, amino acids from the arginine family and their related metabolites like agmatine and polyamines can exert direct regulatory effects on gut function and integrity
• there is emerging evidence that the degradation of serine and aspartate, which was reduced in the presence of larger amounts of glutamine, is a major factor contributing to the (over-)colonization of the small intestine with bacteria and the production of virulence factors in the intestine

Despite the fact that these results were obviously obtained by scientists interested in the development of effective feeding strategies for foodstock (ruminents with their large amount of bacteria in particular), the notion that higher glutamine intakes may exert (likely) beneficial effects on both amino acid availability, as well as gastrointestinal integrity and overall health appears to confirm the existing anecdotal evidence that glutamine-rich foods and supplements could make an important, if not essential contribution to your gastro-intestinal and metabolic health.