Disentangling Gut Microbiome Alterations in Children with Cow's Milk Allergy: Impact of Sex, Milk Elimination, and Family History of Allergies.

CMA-associated gut microbiome compositional differences were more pronounced in girls than in boys.

• PERMANOVA analyses were used to evaluate overall compositional differences between CMA and healthy control groups
• Study included 32 children with CMA (14 with active CMA, 18 with developed oral tolerance) and 36 age-matched healthy controls (51.5% male), aged 5-12 years
• 16S rRNA gene sequencing was used to characterize the intestinal microbiota
• The effects of CMA on the gut microbiome were described as 'more pronounced in girls'

Girls with CMA showed specific decreases in bacteria potentially related to protection from allergy, including Monoglobus and Anaerostipes.

• Differential abundance analyses were employed to identify bacteria varying between groups
• Decreases in Monoglobus and Anaerostipes were identified as female-specific findings
• These taxa were characterized as 'potentially related to protection from allergy'
• No equivalent female-specific protective bacteria decreases were reported in boys

Girls' gut microbiomes were more influenced by a family history of allergy than boys', and remained farther from the healthy state upon development of oral tolerance.

• Exploratory analyses investigated whether family history of allergies underlies sex-associated microbiome differences
• Girls' microbiomes were found to be 'more influenced by a family history of allergy'
• Upon development of oral tolerance (DOT), girls' microbiomes remained 'farther from the healthy state' compared to boys
• 18 of the 32 CMA children had developed oral tolerance at time of sampling

Milk elimination affected more microbial taxa in boys in the control group than in girls in the control group, although it altered global microbiome composition in both sexes.

• Analysis compared the effect of milk elimination on healthy control boys versus healthy control girls
• The number of differentially abundant taxa was greater in boys than in girls in the control group under milk elimination
• Despite differences in number of taxa affected, global microbiome composition was altered by milk elimination in both boys and girls
• These findings were derived from exploratory analyses of the control group

Milk elimination and family history of allergies failed to explain most gut microbiome alterations observed in CMA, indicating these alterations are specifically linked to disease development.

• Exploratory analyses specifically investigated milk elimination and family history as potential confounders of CMA-associated microbiome differences
• Neither milk elimination nor family history could account for the majority of microbiome alterations seen in CMA children
• Authors concluded that microbiome alterations are 'specifically linked to disease development' rather than to these external factors
• This finding applied across both sexes

The study population consisted of 32 children with CMA and 36 age-matched healthy controls, with microbiota characterized by 16S rRNA gene sequencing.

• CMA group: 32 children aged 5-12 years, of which 14 had active CMA and 18 had developed oral tolerance
• Control group: 36 age-matched healthy controls, 51.5% male
• Intestinal microbiota was profiled using 16S rRNA gene sequences
• PERMANOVA and differential abundance analyses were the primary statistical methods employed