Answer by Tirumalai Kamala:
Recently, several studies have compared gut microbiota composition between obese and lean humans.
- Goodrich, Julia K., et al. “Human genetics shape the gut microbiome.” Cell 159.4 (2014): 789-799.
- Ridaura, Vanessa K., et al. “Gut microbiota from twins discordant for obesity modulate metabolism in mice.” Science 341.6150 (2013): 1241214.
- Vijay-Kumar, Matam, et al. “Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.” Science 328.5975 (2010): 228-231.
- Turnbaugh, Peter J., et al. “A core gut microbiome in obese and lean twins.” nature 457.7228 (2009): 480-484.
These studies showed the following:
- That they are different between obese and lean individuals.
- The obese-associated gut microbe families tend to maximize energy extraction from food.
- Fecal transplant from humans to germ-free mice tends to recapitulate the human donor weight in the mouse recipient, namely, mice that get fecal microbiota from obese showed greater weight (fat) gain while those that got it from lean tended to stay lean.
Why did this woman need a fecal transplant in the first place? She had Clostridium difficile (C.diff) infection, one of the most serious and difficult-to-treat GI tract infections. A healthy gut is stably colonized by various commensal microbes. Ensconced in their niches, they perform a great variety of functions conferred by their residential needs. C.diff does not colonize a healthy gut. Its presence indicates a greatly disturbed GI tract, where these microbial niches are no longer stably colonized by commensal gut microflora. Unlike a healthy gut, when donor gut microbiota are transferred to such a gut, they would find many niches readily available for occupation. Such gut commensal microbe instability and niche openings dictate that post-fecal transplant, the recipient gut microflora would mirror the donor gut microflora, and if the latter predominated in obese-associated microbial species, so would the former.
In a series of landmark studies in the 1960s, the great Humanist and Renaissance scientistshowed that fecal transplant alone is sufficient to stably transfer, from a donor to a recipient, traits that then persist for the life of the recipient. In these experiments, newborn (2-day old) mouse pups received adult mouse fecal matter from a mouse strain that greatly differed in its growth rate, body size and gut microbiota composition. A single such fecal matter transplant alone was sufficient to transfer for life, key donor mouse strain traits, namely, growth rate, body weight and resistance to infections ( ).
What’s the relevance of Dubos’ observation to this case study? They both have in common the most important variable, recipient gut microbial composition instability, in Dubos’ case, the instability of the newborn mouse gut not yet stably colonized by commensals, in the case study, instability due to unknown reasons but instability nevertheless given the hallmark signature of C. diif infection. As a result, in both cases, the recipient gut has niches available for stable colonization by donor microbes, microbially speaking a blank slate if you will, and the recipients thus tend to recapitulate the hallmark metabolic features of the donors. In the case study, the recipient weighed 136 pounds at the time of request. At her request, her donor was her 16-year old daughter, approx. 140 pounds at the time of the transplant, and 170 pounds later (not specified when). Recipient’s weight gain mirrors the donor’s suggesting a role for the donor gut microbiota.