Active Machine learning for formulation of precision probiotics.

ABSTRACT

It is becoming clear that the human gut microbiome is critical to health and well-being, with increasing evidence demonstrating that dysbiosis can promote disease. Increasingly, precision probiotics are being investigated as investigational drug products for restoration of healthy microbiome balance. To reach the distal gut alive where the density of microbiota is highest, oral probiotics should be protected from harsh conditions during transit through the stomach and small intestines. At present, few probiotic formulations are designed with this delivery strategy in mind. This study employs an emerging machine learning (ML) technique, known as active ML, to predict how excipients at pharmaceutically relevant concentrations affect the intestinal proliferation of a common probiotic, Lactobacillus paracasei. Starting with a labelled dataset of just 6 bacteria-excipient interactions, active ML was able to predict the effects of a further 111 excipients using uncertainty sampling. The average certainty of the final model was 67.70% and experimental validation demonstrated that 3/4 excipient-probiotic interactions could be correctly predicted. The model can be used to enable superior probiotic delivery to maximise proliferation in vivo and marks the first use of active ML in microbiome science.