A few weeks ago, on a warm midsummer evening, Dr Derek Holdsworth and I listened with a mixture of awe and interest as our one time research fellow, Professor Satish Rao, now Chief of Gastroenterology at Medical College of Georgia, Augusta University, Augusta, GA entertained us with changing perceptions of IBS.
America has always had a different perspective; highly evidence based and more operational. There are notable differences. Small intestinal bacterial overgrowth is a more popular diagnosis in the United States. Some researchers have put the prevalence as high as 80%, but that is probably skewed by misinterpretation of the results of the lactulose hydrogen breath. The reality is probably that about 30% of people with IBS have SIBO, still much greater than when Satish worked with us in the nineteen eighties. ‘So what is the reason for that’, I asked. ‘Almost certainly, proton pump inhibitors ‘, was the reply.
Proton pump inhibitors or acid blockers, omeprazole and lanzoprazole were introduced twenty years ago to treat symptoms of peptic ulcer and oesophageal reflux. Within a year, rates of surgery for acid peptic disease had plummeted. But blocking gastric acid secretion has some unintended consequences; one is that it allows bacteria and fungi taken in with the food to proliferate in the stomach and invade the small intestine. This causes fermentation of protein and carbohydrate, denatures fat and bile acid to more irritant compounds and makes the gut more leaky. These physiological actions not only produce all the symptoms of IBS but could also, Satish explained, cause tiredness and confusion.
He described one of his patients, a woman of 51, who got ‘brain fog’ and bloating whenever she drank milk. She had been on long term proton pump inhibitors for symptoms of reflux and was using large doses of probiotics containing lactobacillus as treatment for her alternating constipation and diarrhoea with gas and bloating. She developed her brain fog and bloating whenever she ate. The inference was that because of the suppression of gastric acid, lactobacilli had colonised the small intestine in large numbers and were fermenting the lactose in milk and other carbohydrate-rich foods, which not only caused gas and bloating , but also generated excess D-lactic acid, which caused fatigue and loss of concentration. Treatment of SIBO and SIFO (small intestinal fungal overgrowth) with a combination of antibiotics eliminated the symptoms.
Lactic acid exists as two optical isomers. L-lactic acid can be produced in mammalian cells by anaerobic metabolism, that can be caused briefly by strenuous exercise when demand for energy exceeds supply, but also during sepsis, diabetic ketoacidosis and many other uncommon medical conditions. D-lactic acid is only produced in large amounts when a diet rich in carbohydrate is fermented. D-lactic acidosis has been described in short bowel syndrome, after intestinal by-pass for treatment of obesity and in severe pancreatic insufficiency. In all of these conditions, the absorptive capacity of the small intestine is so curtailed that abnormally large amounts of carbohydrate are fermented in the colon, but it has not to my knowledge been described in patients on a high FODMAP diet containing excessive amounts of poorly absorbed fermentable carbohydrate.
Recent evidence suggests excessive production of D-lactic acid may also be produced artificially by the ingestion of megadoses of probiotics containing lactobacillus acidophilus when gastric acid secretion is suppressed by acid blockers. Under those conditions, fermentation of milk and possibly also pulses in the stomach and the small intestine, would generate toxic amounts of D-lactic acid.
Excess D-lactate is toxic to both brain and heart cells that have a high demand for energy generated by glycolysis and oxidative phosphorylation. In the mitochondria, build up of D-lactate interferes with mitochondrial utilisation of two major energy products of glycolysis, L lactate and pyruvate, and reduces oxygen consumption. In this oxygen-starved environment, cells are unable to produce adequate amounts of adenosine triphosphate (ATP), necessary for the normal turnover of neurotransmitters and the firing of neurones. This gives rise to symptoms of incoordination, fatigue and confusion (brain fog).
Rehman A BC, Patel N, et al.. Brain Fogginess, Gas, Bloating and Distension: A Link Between SIBO, Probiotics and Metabolic Acidosis. Gastroenterology 2014;146:S850-S1.