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Microbiome. 2018 Sep 21;6(1):171. doi: 10.1186/s40168-018-0545-x.

A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space.

Author information

The Microsoft Research-University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.
The Liggins Institute, the University of Auckland, Auckland, New Zealand.
AgResearch, Food & Bio-based Products, Palmerston North, New Zealand.
Riddet Institute, Palmerston North, New Zealand.
Malaghan Institute of Medical Research, Wellington, New Zealand.
Discipline of Nutrition, School of Medical Science, University of Auckland, Auckland, New Zealand.
Department of Computer Science, University of Pisa, Pisa, Italy.
The Microsoft Research-University of Trento Centre for Computational and Systems Biology, Rovereto, Italy.
National Science Challenge "High Value Nutrition", Auckland, New Zealand.



Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space.


Using public domain literature mining and an in silico reverse metabolic approach, we constructed probiotic-prebiotic-food associations, which can guide targeted feeding of immune health-beneficial microbes by weaning food; analyzed competition and synergy for (prebiotic) nutrients between selected microbes; and translated this information into designing an experimental complementary feed for infants enrolled in a pilot clinical trial ( ).


In this study, we applied a benefit-oriented microbiome research strategy for enhanced early-life immune health. We extended from "classical" to molecular nutrition aiming to identify nutrients, bacteria, and mechanisms that point towards targeted feeding to improve immune health in infants around weaning. Here, we present the systems biology-based approach we used to inform us on the most promising prebiotic combinations known to support growth of beneficial gut bacteria ("probiotics") in the infant gut, thereby favorably promoting development of the immune system.


Complementary feeding; Infant gut microbiome; Infection; Knowledge extraction; Prebiotic; Probiotic; Reverse ecology; Systems biology

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