Evaluation of Stool Short Chain Fatty Acids Profiles in the First Year of Life With Childhood Atopy-Related Outcomes

Abstract

IntroductionShort chain fatty acids (SCFAs) are the main intestinal intermediate and end products of metabolism of dietary fibers/polyphenols by the gut microbiota. The aim of this study was to evaluate the biological implication of stool SCFA profiles determined in the first year of life on the clinical presentation of allergic outcomes in childhood.MethodsFrom the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort, a sub-cohort of 75 participants was recruited. Scheduled questionnaire data was collected for cumulative prevalence of physician-diagnosed eczema, wheezing with the use of nebuliser, and allergen sensitization till the age of 8 years. Stool samples collected at week 3 and months 3, 6 and 12 were quantitated for 9 SCFAs using LC/MS/MS. SCFA data were grouped into lower (below the 25th) and higher (above the 75th percentiles) categories. Generalized Linear Mixed Models was employed to analyse longitudinal association between SCFAs and atopy-related outcomes.ResultsChildren with lower stool butyric acid levels (≤25th percentile) over the first 3 time points had higher odds ratio (OR) for wheezing (adjOR = 14.6), eczema (adjOR = 13.2), food sensitization (adjOR = 12.3) and combined outcomes of both wheezing and eczema (adjOR = 22.6) till age 8 years, compared to those with higher levels (≥75 percentile). Additionally, lower longitudinal levels of propionic acid (≤25th percentile) over 4 time points in first year of life was associated with recurrent wheezing (≥2 episodes) till 8 years (adjOR = 7.4) (adj p < 0.05).ConclusionOur results suggest that relatively low levels of gut SCFAs in early life are associated with increased susceptibility to atopic-related outcomes in childhood.

The role of short-chain fatty acids in inflammatory skin diseases

“…Lower levels of fecal butyrate and valerate have been observed in 6-month-old infants with eczema, and butyrate levels, in particular, have negative correlation with the development of eczema ( Wopereis et al, 2018 ; Kang M. J. et al, 2021 ). This is consistent with the inverse correlation between low microbial complexity in early infancy and the likelihood of allergies in later life ( Wang et al, 2007 ; Bisgaard et al, 2011 ; Ismail et al, 2012 ; Victora et al, 2016 ; Roduit et al, 2019 ; Cheng et al, 2022 ). Furthermore, most patients with eczema have low levels of SCFAs, and low fecal valerate levels in childhood is related to a higher incidence of eczema in youth ( Gio-Batta et al, 2020 ; Batta et al, 2021 ).…”

Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases

“…Reduced exposure to SCFAs early in life may be one of the factors responsible for the development and course of the disease, which seems to confirm the work of Roduit et al They found that in a one-year-old pediatric population, a lower fecal level of propionate and butyrate was associated with a markedly higher prevalence of atopic diseases diagnosed at the age of 6 [ 40 ]. Other studies seem to confirm these results by showing that lower fecal butyrate levels in one-year-old patients are associated with the development of eczema [ 41 , 42 , 43 ]. Additionally, decreased exposure to valerate is supposedly correlated with a lower prevalence of eczema in children [ 44 , 45 ].…”

“…These findings are supported by the fact that fecal concentrations of acetate, propionate, and butyrate are lower in patients suffering from IgE-mediated food allergies [ 55 ]. Interestingly, like in the case of atopic dermatitis, lower exposure to SCFAs in early childhood might result in the development of food allergy, and also IgE-associated diseases such as asthma [ 40 , 42 , 45 ]. Moreover, it seems that the protective effect of SCFAs is distinctively observable in IgE-related conditions, contrary to IgE-independent sensitizations [ 56 ].…”

Microbiome Therapeutics for Food Allergy

“…In human studies, low levels of SCFAs have been associated with allergic symptoms in early life, and metagenomic analyses have shown that the microbiota of children who later develop allergic sensitization have reduced potential for butyrate production [ 86 , 87 , 88 , 89 , 90 ]. Variations in SCFA levels in the setting of gut dysbiosis have been linked to cow’s milk allergy, and enrichment with butyrate-producing microbiota promotes cow’s milk allergy resolution [ 50 , 91 , 92 ].…”