Review Article

Biological Mechanisms for Symptom Causation by Individual FODMAP Subgroups

The Case for a More Personalised Approach to Dietary Restriction

Xiao Jing Wang; Michael Camilleri; Stephen Vanner; Caroline Tuck


Aliment Pharmacol Ther. 2019;50(5):517-529. 

In This Article

Potential Interaction of Dietary FODMAPs and the Microbiome

Recent observations from studies altering FODMAP intake suggest the mechanisms may be more complex than fermentation and osmotic effect (Table 4). The composition of gut microbiota can predict the response to FODMAPs,[54,55] and FODMAPs can alter the microbiota composition.[3,56] Evidence from rat studies suggests that a high-FODMAP diet increases rat faecal Gram-negative bacteria, elevates lipopolysaccharides, and induces intestinal pathology, as indicated by inflammation, barrier dysfunction and visceral hypersensitivity;[57] it is unclear whether this extreme inflammatory effect associated with passage of FITC-Dextran with molecular weight 4000 Da represents a model of the human exposure to FODMAPs. Recently, in a pilot study of 16 healthy individuals, a low-fibre, high-simple sugar diet decreased microbial diversity in duodenal aspirate. This correlated with increased permeability in duodenal mucosa in vitro as measured by 4000 Da FITC-Dextran.[58] This supports the preclinical study that changing carbohydrate intake may alter barrier function which may, at least in part, be driven by the gut microbiota. Furthermore, they detected significant differences in the microbiota in healthy volunteers and patients with functional bowel disorders and suggest the diet effects are highly dependent on the nature of the individual's microbiota.

Both IBS patients and healthy controls on a low-FODMAP diet have been shown to have a lower abundance of Bifidobacterium species in faecal samples compared to those on a sham diet.[3,59] Co-administration of multi-strain probiotic as well as oligofructose[59] was able to increase the numbers of Bifidobacterium species but did not contribute to further symptom alleviation.[3] Alterations to types and quantity of bacteria will likely impact on gas production and possibly other metabolites and hence colonic adaptation via pre- or probiotic supplementation could be a future therapy to mitigate effects of FODMAPs. In healthy controls, lower FODMAP intake created a shift toward methane production, which may reduce gas volumes as 4 litres of hydrogen are consumed by methane producing bacteria to create 1 L of methane.[6] A negative correlation has been shown between symptoms scores in lactose intolerant patients and the total number of bacteria, suggesting that higher numbers of bacteria may result in higher fermentative capacity resulting in lower symptoms to malabsorbed lactose.[60] Whether this applies to other FODMAP subgroups has not been evaluated and should be investigated in carefully designed re-challenge studies.

Another potential mechanism regarding the interaction between diet and the microbiome is the development of immune consequence. A single-blind controlled trial by McIntosh et al comparing low to high-FODMAP diets showed the low-FODMAP diet to be associated with changes in urinary histamine, p-hydroxybenzoic acid and azelaic acid (P < 0.01). Specifically, the low-FODMAP diet is associated with an eightfold reduction in histamine in a subset of patients with increased Actinobacteria richness and diversity whereas a high-FODMAP diet resulted in an increase in histamine in a patient subset and a decrease in gas consuming bacteria.[11] Changes to histamine levels suggest that higher FODMAP intake can influence immune activation, although this has not been directly measured. Reductions in pro-inflammatory cytokines following a low-FODMAP diet further support the immune modulation hypothesis.[61] On the contrary, increased proteolytic fermentation and decreased saccharolytic fermentation with 4 weeks of FODMAP restriction based on SCFA production in one study suggests potential detrimental effects but was not correlated with symptoms.[62] However, in a feeding study there was no difference in SCFA production between baseline and following a low-FODMAP diet.[56] Inconsistencies between studies may be related to differences in habitual diets or differences in sample collection and analysis methodologies. The impact of these changes on gut function and symptoms remains to be elucidated.

The microbiome has also been evaluated as a potential means for predicting response to a low-FODMAP diet. Table 7 summarises the studies and microbiome profiles that may potentially differentiate responders to dietary intervention or probiotic therapy and allow personalisation and tailored dietary advice.