Exclusive Enteral Nutrition Significantly Alters Gut Microbiota in IBD

Crohn disease and ulcerative colitis comprise the 2 primary subtypes of inflammatory bowel diseases (IBD). IBD currently has no known cure and whose pathogenesis is not well understood. However, an increasing amount of research points to genetic risk factors combined with antibiotic use and changes in intestinal microbiota as triggers for the onset of IBD.^1,2 IBD diagnosis is rising steadily worldwide and tends to be diagnosed in early adulthood, when it is perhaps most detrimental to lifestyle and productivity.³

Because IBD presently has no known cure, the current strategy for disease management is inducing and maintaining remission through surgery, nutrition, and medical therapies.⁴ Diet has been shown to rapidly change the microbiome of the human gut⁵. Exclusive enteral nutrition (EEN), a nutritional strategy involving liquid diets, has demonstrated efficacy in altering the activity and structure of intestinal microbiota and consequently improving clinical disease.^6,7 This article will present the current research surrounding EEN in the context of IBD and the human gut microbiome.

How Intestinal Microbiota Impact IBD

Although researchers have attempted to identify a single microorganism responsible for IBD,⁸ conclusive evidence for a single causative microorganism has yet to be discovered.⁹ Rather, recent studies have shown that dysbiosis, or changes in flora patterns, play a larger role in the pathogenesis of IBD.⁹

Bacterial groups in the human gut exist in a specific balance, and certain disturbances to this balance may lead to IBD.⁹ For example, a decrease in the abundance of Faecalibacterium prausnitzii, a member of the Firmicutes group, has been linked with a greater risk for ileal Crohn disease.¹⁰ One important property of this particular type of bacteria is its protective effect against inflammation. This effect stems from a 15 kDa protein, which impedes the NF-κB pathway in epithelial cells within the intestine.¹¹

The role of intestinal microbiota in IBD pathogenesis has also been supported by several studies with animal subjects. When genetically at-risk mice (those without interleukin-10) were removed from a sterile environment and placed in a standard setting, inflammation developed; a VSL-3 probiotic mixture returned the mice to normal.¹²

EEN and Maintenance Enteral Nutrition

The purpose of EEN is to induce remission in IBD by altering the landscape and balance of intestinal microbiota. This is performed through diet alone. For a period normally ≤8 weeks in length, an exclusively liquid diet is consumed, with no intake of normal food.⁶ It has also been known for decades that EEN helps manage IBD.¹³ At present, EEN has demonstrated greater efficacy among children,^6,7 though it is effective in adults as well. Consequently, ENN has become the first line therapy for Crohn disease in children and is associated with high efficacy and an 80% rate of remission.¹⁴

The benefits of EEN extend beyond IBD treatment and include normalizing serum bone turnover markers,^15,16 increasing muscle mass,¹⁶ and improving nutritional status.¹⁴ EEN is superior to corticosteroids in achieving these outcomes¹⁴ while also avoiding their adverse side effects.⁴ An occasionally reported side effect of EEN is refeeding syndrome, in which returning to normal nutritional intake after partial or full fasting results in electrolyte abnormalities.¹⁷

After achieving EEN-induced remission, maintenance enteral nutrition is often recommended to sustain remission and avoid relapse.¹⁸ Maintenance enteral nutrition includes a conventional diet supplemented by enteral formulae. This diet improves growth and nutrition, particularly among pediatric patients.

The Effects of EEN on the Microbiome Environment

EEN has demonstrated significant modifying effects on intestinal microbiota.^19,20,21 In a 2008 study by Leach et al, microbiota changed significantly but varied across participants. Moreover, a significant association was observed between changes in Bacteroides composition and inflammation/decreased disease activity.²¹ EEN also reduces the diversity of bacteria in the gut and maintains these modulations.²¹

A separate study on 15 children with Crohn disease demonstrated that concentrations of both Bacteroidetes and Faecalibacterium prausnitzii decreased with EEN.²² Not only did this finding contradict earlier research,¹¹ but participants paradoxically improved despite lower concentrations of the bacteria that were presumed to be protecting them from the disease.²² Fecal sulfides and pH were shown to increase due to EEN, while the important short chain fatty acid, butyrate, decreased.²² The lack of dietary fiber in the EEN diet may cause the observed decrease in bacteria that perform fermentative actions, as well as in butyrate. Supplementing EEN with butyrate may compensate for this deficiency.⁹

A 2016 study of 15 children and teenagers with Crohn disease showed a similar reduction in the Bacteroidetes bacteria group and an increase in Firmicutes bacteria at 2 weeks post-EEN initiation.²³ Although those with a longer disease history showed different microbiota changes from those who were newly diagnosed, EEN was associated with notable improvement in clinical parameters and normalization of immune regulatory function.²³

Conclusions

Intestinal microbiota play an important role in the course of IBD, especially Crohn disease, with alterations in their balance coupling with genetic risk factors to induce these diseases. The reports summarized in this work have presented differing conclusions on changes in certain strains of bacteria. The most noteworthy paradox is F. prausnitzii, which has been assumed to exhibit a protective effect on Crohn disease. However, new research has shown that disease activity and inflammation both improve with its reduction during EEN.²² Although the exact mechanisms through which EEN intervention alters the microbiota landscape requires further study, it has demonstrated efficacy as an intervention in Crohn disease, IBD, and other diseases involving inflammation.

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