Don’t put all your eggs in one basket. Investors who were all in on Enron Corporation or Pets.com could warn you of that. Same goes for how our bodies invest in the microbiome. Investing in the microbiome? Is that a thing? In a way, yes. The microbiome requires investments of all sorts – those investments keep the microbiome ecosystem on a leash, as Kevin Foster and colleagues have described.
The adaptive immune system involves complex system of inputs that may have evolved to manage the microbiome portfolio. One apparent goal of the immune system is to encourage a diverse microbiome.
It is clear that for the gut microbiome throughout most of our lives, having a diverse assemblage of microbes is optimal for our health. Can we think of these as investments, though? Actually we can. We invest in secretory IgA that coat various bacteria. We expend resources on complex carbohydrates that feed various members of the microbiome. We provide mucus habitat for phages, and so on.
Having a diverse gut microbiome (microbiome richness) is protective against a great many disorders – from inflammatory bowel disease to lifetime cardiovascular disease risk. Lower diversity is associated with aging, nursing home residence, low fiber diet high in processed food, and in hospitalized patients. Like an investor seeking to minimize risk, keeping a diverse microbial portfolio can, in some cases, prevent losses. In the long term, as in investing, it can be the strategy that pays off the most.
Sometimes having a concentrated portfolio pays higher dividends. As Warren Buffet says, selecting a few high performing stocks from well run companies is the best way to invest, for experts like him. Human life history includes life stages where a concentrated microbiota portfolio seems to be the way to go. Infancy is one such life stage – the gut microbiota of breast milk fed babies is dominated by one microbial taxon: Bifidobacteria spp. This requires a very specialized investment from the mother in the form of breast milk. Breast milk has evolved to preferentially feed very specific species and strains of Bifidobacteria – breve, longum subspecies infantis, and so on.
Provision of breast milk is akin to being an angel investor. Angel investors make early stage bets in enterprises that are not yet self sustaining, like infants! That costly, well targeted, investment is necessary to propel the enterprise to the next stage – weaning and toddlerhood.
The breast-fed microbiota shows that when all of the nutrient input can be controlled, a greater degree of control over the microbial portfolio is possible. After weaning, such specialized investment is impossible, and nutrient input cannot be so carefully controlled, so we adopt the long term investor strategy of diversification – mostly.
Diversification is not typical in all body site microbiomes during adulthood. In the adult female reproductive tract, a low diversity microbiome dominated by Lactobacillus species is associated with health. This adult exception proves the rule however. Here too, a concentrated portfolio only happens with very targeted investments. The vaginal epithelial cells secrete specialized carbohydrates that preferentially feed protective species of Lactobacillus. This would not happen without strict control of the nutrient milieu in the vagina, and without an investment in secreted carbohydrates that comes with a metabolic cost to the host.
When the nutrient environment can no longer be controlled, for instance during diabetes when high blood sugar causes secretions in the body to be elevated in glucose, the body loses control of its microbial investment portfolio. In the female reproductive tract, a concentrated portfolio of Lactobacillus gives way to overgrowth of pathogenic species. Bacterial vaginosis is a dysbiosis of the vaginal microbiome, one associated with lower fertility, and with uncomfortable symptoms. This higher diversity state can be thought of as a hostile takeover by pathogenic species.
Hostile takeovers happen in the gut microbiota too. Clostridium difficile overgrowth happens when antibiotics disrupt the microbial ecosystem, replacing a high diversity state with a very low diversity state. Similar takeovers happen in the intensive care unit, when antibiotic resistant strains of gram negative bacteria and Candida replace the preexisting diverse microbiota. These are ultra low diversity states associated with higher mortality.
Can you think of other analogies between investment strategies and how our bodies cultivate the microbiome? Please comment below.
Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine
Hi Joe: This is great! I am teaching med students, and am wondering if I can include a lecture slide summary and link to this page (with proper attribution)? I will call it the “Alcock Analogy.” Thanks!, Randy
You bet. I am glad you like the analogy. I have more I intend to write about this. It will be interesting to hear your your students respond to these ideas.