Abstract Paediatric Crohn’s disease (pCD), once primarily observed in Western countries, is now experiencing a global increase in incidence rates. Southeast Asian nations, including Malaysia, are now witnessing a gradual increase in incidence of pCD. In addition to clinical symptoms, children with Crohn’s disease (CD) also have mental and emotional impairments. Children with CD experience gut microbiota dysbiosis. Exclusive enteral nutrition (EEN) is the recommended first line treatment for mild-to-moderate pCD due to its multifaceted disease-modulating effects, including positive re-modulation of the diseased gut microbiota. However, there exists a critical knowledge gap regarding the understanding of gut microbiota dynamics in individuals with CD treated with EEN, particularly in Southeast Asian regions like Malaysia. This study aimed to fill this void by investigating the gut microbiota profile of Malaysian children with CD, making it the first of its kind in Malaysia. Using targeted 16S ribosomal DNA (16S rDNA) next-generation sequencing, the study identified a microbiota profile dominated by Fusobacterium nucleatum, Haemophilus parainfluenzae, Fusobacterium mortiferum, Acidaminococcus, and Monoglobus among patients with pCD, with the latter three being newly identified in relation to pCD. Following successful EEN treatment, enrichment was observed in bacterial groups such as Lachnoclostridium, Parabacteroides, and Eubacterium fissicatena group. The groups of Clostridium sensu stricto 13 subterminale, Acetivibrio ethanolgignens group, and Robinsoniella peoriensis, which have not been previously associated with pCD, were also found to be increased following EEN treatment. While some similarities with previous literature were noted, Malaysians with pCD treated with EEN exhibited several novel bacterial groups associated both during disease and treatment. This study sheds light on the interplay between gut microbiota and pCD pathology, emphasising the versatility of nutritional therapy approaches in diverse populations. Further research in this area holds promise for refining treatment strategies and improving outcomes for pCD individuals, not only in Malaysia but globally.
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