New insights regarding gut microbiota as a potential target for prevention of allergic disease in childhood

The prevalence of childhood allergic diseases is increasing throughout the world. Although previous research (here; here) has found that gut microbial colonization dynamics differ between allergic and healthy infants, little is known regarding the extent to which specific changes in gut microbiota composition in early life could be used as potential biomarkers of later allergic disease, or could be used to prevent such disease.

A recent case-control study, led by Dr. Christophe Lay from Nutricia Research and Department of Paediatrics at National University of Singapore in Singapore, has found that an elevated Klebsiella/Bifidobacterium (K/B) ratio could be used as a potential gut microbiota biomarker of allergic disease in childhood.

In a Chinese sub-cohort of 21 allergic and 18 healthy infants, the researchers analysed intestinal microbial composition and diversity via 16S ribosomal ribonucleic acid (rRNA) gene sequencing at 3 weeks, 3 months and 6 months of age. Researchers also tracked allergic infants for cumulative incidence of allergic manifestations (allergic eczema, allergic rhinitis and asthma) at ages 18 and 36 months, in order to correlate gut microbiota analysis with allergy later during childhood.

Although the faecal microbiota profiles of allergic infants and healthy controls were similar at 3 weeks and 6 months of age, significant differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. Gut microbiota of healthy infants was enriched with commensal Bifidobacterium species (B), whereas gut microbiota of allergic infants showed a higher abundance of the opportunistic pathogen Klebsiella (K). Analysis at the individual level showed that 12 allergic infants had a high K/B ratio above the population median K/B ratio. In addition, a high K/B ratio compared to a low K/B ratio led to an increased odds ratio of developing allergy by 3 years of age.

Dysbiotic composition and functional diversity of gut microbiota in early life may disrupt development of the immune system and may be associated with food allergies such as cow’s milk allergy (CMA). However, whether targeting gut microbiota in early life with prebiotics and probiotics, or their combination (synbiotics), could help prevent food allergy development little is not known.

A new randomized controlled trial, led by Dr. Louise Jane Michaelis from the Great North Children’s Hospital at Newcastle upon Tyne (United Kingdom), has found that a synbiotic-containing amino acid-based formula may improve gut microbiota in non-inmunoglobulin E (IgE)-mediated allergic infants under 13 months.

The researchers investigated the effects of a synbiotic-containing amino acid-based hypoallergenic and nutritionally complete formula (AAF) (consisting of a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V at a concentration of 1.47 x 10⁹ colony-forming units (CFU)/100 mL formula) on faecal microbiota composition and clinical outcomes in infants with suspected gastrointestinal non-IgE mediated cow’s milk allergy (CMA). Faeces from age matched healthy breastfed infants were used as reference. CMA subjects were randomized and received test or control formula –AAF without synbiotics– for 8 weeks.

At week 8, median percentage of bifidobacteria was higher in the test group (n = 35) vs. the control group (n = 36) (35.4% vs. 9.7%, respectively), whereas E. rectale/C. coccoides (ER/CC) was lower (9.5% vs. 24.2%, respectively). Levels of bifidobacteria and ER/CC in the test subjects approximated levels in healthy breastfed infants (55% and 6.5%, respectively).

Regarding clinical outcomes, exploratory gastrointestinal and general symptoms improved over time and were not statistically different between test and control at week 8.

In conclusion, the study mentioned above is the first to demonstrate that the ratio of genera Klebsiella and Bifidobacterium during early infancy could be used as a potential biomarker for allergy development later in childhood. Further research with longer follow-up will depict a clearer picture regarding the role of an elevated K/B ratio in the development of allergic disease. Furthermore, the second study shows AAF with a synbiotic can modify gut microbiota in subjects with suspected non-IgE CMA, allowing infants with non-IgE CMA to achieve a microbial composition close to that seen in healthy breastfed infants.

References:

Low JSY, Soh SE, Lee YK, et al. Ratio of Klebsiella/Bifidobacterium in early life correlates with later development of paediatric allergy. Benef Microbes. 2017; 8(5):681-95. doi: 10.3920/BM2017.0020.

Candy DCA, Van Ampting MTJ, Oude Nijhuis MM, et al. A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants. Pediatr Res. 2017. doi: 10.1038/pr.2017.270.