Comparative Analysis of Original and Replaced Gut Microbiomes within Same Individuals Identified the Intestinal Microbes Associated with Weight Gaining

The precise mechanisms of action of the host’s gut microbiome at the level of its constituting bacteria are obscure in most cases despite its definitive role. To study the precise role of the gut microbiome on the phenotypes of a host by excluding host factors, we analyzed two different gut microbiomes within the same individual mouse after replacing the gut microbiome with a new one to exclude the host factors. The gut microbiome of conventional C57BL/6 mice was randomly reestablished by feeding fecal samples from obese humans to the mice, and depleting their original gut microbiome with an antibiotic and antifungal treatment. Comparison of body weight changes before and 3 months after the replacement of the gut microbiome showed that the gut microbiome replacement affected the body weight gain in three different ways: positive, medium, and negative. The differences in body weight gain were associated with establishment of a different kind of gut microbiome in each of the mice. In addition, body weight gaining was negatively associated with the Firmicutes/Bacteroidetes ratio, which is consistent with previous recent findings. Thorough statistical analysis at low taxonomic levels showed that uncultured bacteria NR_074436.1, NR_144750.1, and NR_0421101.1 were positively associated with body weight gain, while Trichinella pseudospiralis and uncultured bacteria NR_024815.1 and NR_144616.1 were negatively associated. This work shows that replacement of the gut microbiome within the same individual provides an excellent opportunity for the purpose of gut microbiome analysis by excluding the host factors.