Diet-induced remission tied to metabolome changes in kids with Crohn’s disease

Crohn’s disease (CD) remission, induced by either CD exclusion diet with partial enteral nutrition (CDED+PEN) or by exclusive enteral nutrition (EEN), leads to significant changes in metabolite levels in paediatric patients, according to a new study.

“We demonstrated that the clinical outcome of CDED+PEN and EEN is strongly associated with some metabolite changes such as kynurenine, ceramides, purine metabolism, vitamins, amino acids, and components of succinate synthesis,” the researchers said, adding that “sustained remission with CDED+PEN, but not EEN, was associated with persistent changes in metabolites.”

They measured a total of 216 faecal metabolites using 80 faecal samples from children with mild-to-moderate CD, who were randomly assigned to receive either CDED+PEN or EEN to induce remission. Samples were collected at weeks 0, 6, and 12.

Partial least squares discriminant analysis revealed that the levels of 20 metabolites were significantly changed by week 6 in those who had achieved diet-induced remission. By week 12, concentrations of 16 metabolites were significantly changed from baseline in patients with sustained remission. Heatmapping revealed that these metabolites were principally components of purine and lipid metabolism. [Gastroenterology 2022;doi:10.1053/j.gastro.2022.05.050]

Pathway analysis also showed that there was a sustained change in the metabolism of proline, purine, and glycerophospholipids at weeks 6 at 12 among patients who had reached remission. While there were no significant differences in metabolite profiles between the CDED+PEN and EEN arms at baseline, such variations arose after 6 weeks of nutritional therapy and were deemed statistically significant.

By week 6, 17 metabolites were enriched, while two were reduced, in CDED+PEN vs EEN patients. Of these, seven were reached significance. Levels of methoxytryptamine, cellobiose, and some ceramides were decreased in the EEN group after 6 weeks, while no such change was reported in the CDED+PEN group. Meanwhile, histidinol was elevated in CDED+PEN vs EEN patients at this time point.

At 12 weeks, patients with EEN-sustained remission showed lower levels of metanephrine, an adrenaline metabolite, as opposed to baseline. In comparison, CDED+PEN patients demonstrated elevated concentrations of serotonin relative to baseline.

Moreover, researchers observed that in the EEN arm, while changes in the levels of agmatine, N-acetylputrescine, and 24,25-dihydrolanosterol persisted until 12 weeks, levels of other metabolites—such as hypoxanthine and aminoadipic acid—returned to baseline concentrations. In contrast, CDED+PEN led to strong and persistent changes in metabolite profile.

“Our study shows that dysbiosis correction and associated metabolome changes may act as key mechanisms mediating nutritional therapy-induced remission,” the researchers said. “It remains difficult to assign cause and effect as the metabolome might change due to a decrease in inflammation or associated with microbiome compositional changes, but several key processes, confirmed with different analytical approaches, can be highlighted.”

“Further study of the link between clinical outcomes, microbiome composition, and metabolome is warranted to improve and ultimately personalize dietary interventions in CD,” they added.