In the absence of profound perturbation, bacterial communities living in the gut are mostly stable over time within an individual and between family members. However, the effect of exogenous dietary factors including both pre- and probiotics is generally variable and depends on individualized features of the background microbiota. In the complexity of gut ecology, understanding which factors drive exogenous strain engraftment may allow a better characterization of microbiome effects on host physiology.
A new study, led by Dr. Justin L. Sonnenburg from the Department of Microbiology and Immunology at Stanford University School of Medicine (USA), has found that diet specifically affects how strains of bacteria colonize and integrate into a complex microbiota in mice.
In order to study to what extent exogenous bacteria integrate into a pre-existing complex gut microbiota, the researchers used a group of mice that had conventional mouse microbiota and two groups of ex-germ-free mice colonized with the gut microbiota from a different healthy human donor. These three groups of mice received a rare strain of Bacteroides ovatus, which was previously isolated for its ability to utilize dietary fructans and marine polysaccharides found in seaweed. When three groups of mice received a custom diet supplemented with porphyrin-rich seaweed (a kind of microbiota-accessible carbohydrate (MAC) found in nori) seven days after inoculation with B. ovatus NB001, a robust increase of up to six orders of magnitude was detected in the strain’s density in feces, irrespective of background microbiota. However, inulin administration to the three groups of mice led to a variable response in the fecal microbiota. These data suggest that it is possible to prioritize the engraftment of one bacterial strain over others by manipulating diet, regardless of the context. The availability of the substrate porphyrin created a privileged niche within the gut that enhanced the engraftment of an exogenous strain competent in its use.
Next, the researchers studied whether varying the dietary substrate dosage influenced the porphyran-digesting bacteria population size and engraftment. When mice were fed the standard chow diet, the porphyran-digesting strain was able to engraft to a limited degree (indeed, one of the groups completely rejected the new strain). In contrast, B. ovatus NB001 engrafted robustly at similar levels in all the mice when they were fed a porphyran-rich diet in the context of a MAC-rich diet. Furthermore, strain abundance was also modified by varying the amount of porphyran supplemented in the diet.
The genes required to enable the digestion of porphyran were engineered into other Bacteroides strains and gave them the same engraftment advantage.
Finally, supplementing porphyran enabled the colonization of the colonic crypt niche by B. thetaiotaomicron harboring the genes involved in porphyran digestion, while germ-free mice were colonized with wild type B. thetaiotaomicron. The challenging strain did not overcome the early colonizer when no porphyran was administered. This challenging strain exclusion by an early colonizer (known as priority effects) highlights the role of specific nutrients in creating an exclusive metabolic niche that affects the gut ecosystem assembly.
In conclusion, these preliminary mice results show that nutrient availability exerts an impact on how new strains colonize a pre-existing complex gut microbiota in mice.
Shepherd ES, DeLoache WC, Pruss KM, et al. An exclusive metabolic niche enables strain engraftment in the gut microbiota. Nature. 2018; doi: 10.1038/s41586-018-0092-4.