Next Generation Probiotics

As we look to the future for probiotics, one thing seems clear: what we see as probiotics today will morph into a much wider range of microbes used for broader purposes. Probiotic yogurt will certainly still be an important product, but drugs targeting human, plant and animal health or disease conditions are sure to emerge.

These ‘next generation probiotics’ are likely to include non-‘traditional’ microbes. Whereas today, probiotic products typically use species of Bifidobacterium, Lactobacillus, Saccharomyces or Bacillus, next generation probiotics will tap novel microbes associated with health from the myriad of human commensals. Other likely next generation probiotics are genetically modified microbes targeting specific therapeutic capabilities and defined consortia designed to cure a disease or restore a depleted microbiota. Targets will include microbiota-impacted physiological functions extending beyond the gut.

Numerous startup companies are underway, dedicated to microbiome-modulating therapies and/or diagnostics (Olle, 2013.Medicines from microbiota. Nature Biotechnology 31:309-15). One of these, Evolve BioSystems Inc , was started by UC Davis scientists and targets probiotics for infant health. It focuses on probiotic bacteria possessing gene systems that will recognize specific prebiotic oligosaccharides derived from human breastmilk. Probiotic bacteria optimized for at-risk infants will be a welcome development from their efforts.

A recent paper (Dao et al. 2016) moves the field a step forward to use of Akkermansia muciniphila as a next generation probiotic to promote metabolic health. The authors previously found in mice a causative role for A. muciniphila in “lowering body fat mass, improving glucose homoeostasis, decreasing adipose tissue inflammation and increasing gut integrity.” But results in humans were inconsistent. The authors therefore looked at A. muciniphila levels in human fecal samples from a previous study, whereby obese or overweight subjects were placed on a calorie restricted diet and after a weight loss period were tracked during a weight stabilization maintenance phase. The subjects separated into two groups, based on high or low abundance of A. muciniphila in feces. The high abundance group was different from the low abundance group in some important ways: The high abundance group had:

  • lower waist-to-hip ratio, leptin and surrogates of insulin sensitivity
  • lower fasting blood glucose and insulin
  • higher insulin sensitivity
  • a greater improvement of total and LDL cholesterol
  • continued decrease in waist circumference during the weigh stabilization period

Overall, the authors observed that the higher abundance group was characterized by a healthier metabolic profile.

The authors also measured microbial gene richness in the fecal samples. Gene richness measures the number of different microbial genes. Subjects with both high gene richness and high A. muciniphila had the best metabolic status. It is not possible to conclude from this study that increasing gene richness and A. muciniphila abundance would improve metabolic status of overweight or obese people, although this is an attractive hypothesis. That question can only be answered by a properly controlled intervention trial that can increase A. muciniphila levels and seeing if health parameters also improve.  A prebiotic-type substrate that selects for A. muciniphila and/or direct administration of A. muciniphila are possible approaches. Using this microbe as an oral probiotic would require a safety assessment for this mucin-degrading species.