Effects of a Specific Synbiotic blend on Fecal Short-Chain Fatty Acids and Gut Inflammation in Cow's Milk-Allergic Children Receiving Amino Acid–based Formula during Early Life: Results of a Randomized Controlled Trial (PRESTO Study)

Pantipa Chatchatee¹Annelot Breedveld²Simone Eussen^2*Anna Nowak-Wegrzyn³Lars Lange⁴Suwat Benjaponpitak⁵Kok Wee Chong⁶Pasuree Sangsupawanich⁷Harm Wopereis²Manon Oude Nijhuis²Jane Langford²Atanaska Kostadinova²Valerie Trendelenburg⁸Robert Pesek⁹Carla Davis¹⁰Antonella Muraro¹¹Michel Erlewyn-Lajeunesse¹²Adam Fox¹³Louise Michaelis¹⁴Kirsten Beyer⁸

• ¹Center of Excellence for Allergy and Clinical Immunology, Division of Allergy and Immunology, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand
• ²Danone Research & Innovation, Utrecht, Netherlands
• ³Allergy and Immunology, Department of Pediatrics, New York University Langone Health, New York, United States
• ⁴St Marien Hospital, Bonn, Germany
• ⁵The Pediatric Allergy and Immunology Division, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
• ⁶The Allergy Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, Singapore, Singapore
• ⁷The Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
• ⁸The Department of Pediatric Pneumology, Immunology and Intensive Care Medicine, Charite - Universitatsmedizin Berlin, Berlin, Germany
• ⁹Arkansas Children's Hospital, Little Rock, United States
• ¹⁰Texas Children's Hospital, Baylor College of Medicine, Houston, United States
• ¹¹The Food Allergy Referral Centre, Padua University Hospital, Padua, Italy
• ¹²University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
• ¹³Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
• ¹⁴Great North Children's Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom

Consumption of an amino acid-based formula (AAF) with added synbiotics (short-chain oligofructose and long-chain inulin (scFOS/lcFOS, 9:1 ratio) and Bifidobacterium breve M-16V) (AAF-S) beneficially impacts the gut microbiome of infants with cow's milk allergy (CMA). We assessed the effect of consuming AAF with or without synbiotics by children with CMA for 12 months on their fecal (branched) short-chain fatty acids (SCFA/BCFA) concentrations, and on gut barrier and inflammation markers (Netherlands Trial Register NTR3725). Feces and saliva were collected from 161 children (≤13 months) with IgE-mediated CMA at baseline, 6 and 12 months after enrollment, and at 24 and 36 months follow-up. Fecal SCFA and BCFA were analyzed by gas chromatography, and gut barrier and inflammation markers were measured in saliva/feces by ELISA or ImmunoCAP. At 6 months, children receiving AAF-S had significantly lower fecal propionate, valerate and BCFA concentrations compared to children consuming AAF. The percentage of propionate from the total 6 SCFA/BCFA (acetate+butyrate+propionate+valerate+isobutyrate+isovalerate) was significantly lower, while the percentage of acetate from the total 6 SCFA/BCFA was significantly higher in the AAF-S group. There were no significant differences between groups in fecal concentrations of butyrate at 6 months, nor in SCFA or BCFA at baseline and after 12, 24 or 36 months. Intestinal inflammation and barrier markers did not differ between groups. Addition of synbiotics to AAF brings concentrations of key fecal microbial metabolites more in line with patterns observed in healthy breastfed infants. The effects on SCFA and BCFA concentrations were transient and only seen at 6 months.