Gut Microbiota Dysbiosis in Suspected Food Protein Induced Proctocolitis – A Prospective Comparative Cohort Trial
Year: 2024
Type: article
Abstract: Food protein induced proctocolitis (FPIP) in infants is characterized by hematochezia caused by inflammation of the distal colon secondary to a delayed-type hypersensitivity reaction to food proteins, typically cow’s milk. Dietary elimination of the offending food protein is associated with resolution of hematochezia. In clinical practice, many infants with suspected FPIP remain on a cow’s milk free diet until 12 months of age, despite previous studies showing that only 15% to 20% of infants develop recurrent hematochezia following re-exposure to the suspected food allergen. Thus, this study aimed to assess whether an early imbalance in infant gut colonization might provide an alternative, nonallergy explanation for the distal colon inflammation seen in infants with suspected FPIP.This study prospectively enrolled infants with suspected food protein induced proctocolitis (sFPIP) who presented with visible hematochezia to an academic medical center and 5 pediatric private practices in Graz, Austria. Patients were included if they had an unremarkable physical examination, blood count, C reactive protein, abdominal ultrasound, and infectious work-up of the stool. Healthy control infants were also recruited at the same 5 pediatric private practices.Stool samples were collected before diagnostic dietary intervention (DDI) (week 0), after 4 weeks of DDI (week 4), and 4 weeks after the end of DDI (week 8). DDI was either a change to extensively hydrolyzed formula or a cow’s milk free diet of the breastfeeding mother. After 4 weeks of DDI, infants returned to their original diet at study inclusion. Stool samples from healthy individuals were collected as controls at the same time points. 16S amplicon and shotgun sequencing was performed in both groups to assess fecal microbiota composition and detailed taxonomic profiling.Fourteen infants with sFPIP were compared with 55 healthy infants. At inclusion (before DDI), sFPIP infants had significant reduction of Bifidobacterium spp (linear discriminant analysis [LDA] = 5.5, P < .001, 12.1% versus 31.3%) and increase of Clostridium sensu stricto (LDA = 5.3, P = .003, 18.3% versus 3.5%) compared with healthy controls. DDI was associated with a significant and sustained increase of Bifidobacterium in sFPIP infants at weeks 4 and 8 (LDA = 5.4, P = .048, 27.9%), whereas in the control group, overall Bifidobacteriaceae abundance did not significantly change.Infants who presented with hematochezia and suspected FPIP had significantly different gut microbiota composition compared with healthy controls. A temporary dietary intervention was associated with a shift back to a microbiota composition comparable to that of healthy infants, which raises the possibility that distal colon inflammation in infants with sFPIP might be triggered by gut microbiota dysbiosis rather than immune hypersensitivity alone.Only a small proportion of well-appearing infants who present with hematochezia are ultimately diagnosed with true FPIP following a diagnostic dietary intervention. Thus, in the majority of remaining infants, the search for an alternative explanation for development of distal colonic inflammation is warranted. This study explores the potential role of early life gut microbiome changes, rather than allergy, in causing distal colitis by demonstrating significant differences in the gut microbial composition of infants with suspected FPIP compared with healthy controls. The predominance of Bifidobacteriaceae in the first months of life in the healthy infant gut has been associated with promoting positive effects of human-bacterial gut epithelium interactions. In this study, the relative decrease of Bifidobacteriaceae in patients with suspected FPIP raises the possibility that loss of gut protective properties provided by this bacterial group could be linked to distal colonic inflammation. Alternatively, it is also possible that inflammatory changes related to immune hypersensitivity could lead to dysbiosis. Indeed, the association between dysbiosis and allergic diseases has previously been reported and is further reinforced by the findings of this study, but a mechanistic understanding and proof of causality remain elusive.
Source: PEDIATRICS
Language: English
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4404925305