Dysbiosis in IBD—Nitrates the Culprit?

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Inflammatory bowel disease (IBD) involves dysbiosis, or an imbalance of beneficial to harmful bacteria in the intestines.1 Specifically, obligate anaerobic bacteria are depleted and the facultative anaerobic bacteria Enterobacteriacea increase. A recent study has found one way in which this dysbiosis develops.2 Researchers from UC Davis discovered that the potentially harmful Enterobacteriacea—specifically, E. coli—use nitrate to grow. Nitrate is formed during intestinal inflammation by our immune system to fight pathogenic bacteria in IBD.  This is a paradox since some species of the potentially harmful bacteria receive plenty of the nitrate fuel to thrive while the beneficial bacteria, which use a much slower fermentation process to grow, lose the upper hand.

State the researchers, “The picture emerging from this study is that nitrate generated as a by-product of the host inflammatory response can be used by E. coli, and likely by other commensal Enterobacteriaceae, to edge out competing microbes that rely on fermentation to generate energy for growth.” They are hoping to find a way to reduce the production of nitrate in the intestines as a way to inhibit the harmful bacteria. “The idea would be to inhibit all pathways that produce molecules that can be used by bacteria such as E. coli for respiration and growth. Essentially you could then smother the bacteria.”

This is interesting and also a paradox because eating large amounts of green leafy vegetables will help to make nitric oxide (NO, which can quickly degrade to nitrate in the gut). We see from this study, as with most everything, it’s a question of balance. In fact, many people throughout the world have too low levels of circulating NO and even take drugs to increase it (including Viagra, as well as nitrate drugs for the heart).

This may help explain why some people with IBS/IBD don’t do well with salads and do better with only cooked, pureed types of food which produce less NO, as well as less fermentation. Perhaps raw vegetables actually provide too much NO fuel to the pathogenic bacteria in these people, ultimately fueling their dybiosis. Does this mean that eating raw vegetables increase dysbiosis in everyone? Absolutely not! In fact, a diet high in raw vegetables actually promotes the growth of beneficial bacteria in most cases. However, when starting a higher-fiber diet which includes prebiotics, or a raw vegetable diet, do it gradually to allow time for the changes in the microbiome, and to avoid IBS-type symptoms such as excess gas, bloating, and abdominal discomfort.

Maybe this is why short courses of antibiotics, (with probiotics and maybe prebiotics) are needed early on, before the situation becomes a chronic imbalance as is seen in so many people with IBS and IBD. This also may be why stool transplants or super probiotics (containing huge and diverse amounts of bacteria) may be needed to overwhelm what is going on in the colon, and to re-establish the balance quickly.

References

  1. F. Fava and S. Denese, “Intestinal microbiota in inflammatory bowel disease: friend of foe?” World J Gastroenterol. 2011 Feb 7;17(5):557-66.
  2. S.E. Winter, et al., “Host-derived nitrate boosts growth of E. coli in the inflamed gut.” Science. 2013 February;339:708–11.