Abstract
Commensal microbes have mutualistic relationships with their host and mainly live in the host intestine. There are many studies on the relationships between commensal microbes and host physiology. However, there are inconsistent results on the effects of commensal microbes on host lifespan. To clarify this controversy, we generated axenic flies by using two controlled methods – bleaching and antibiotic treatment – and investigated the relationship between the commensal microbes and host lifespan in Drosophila melanogaster. The removal of microbes by using bleaching and antibiotic treatments without detrimental effects increased fly lifespan. Furthermore, a strain of flies colonized with a high load of microbiota showed a greater effect on lifespan extension when the microbes were eliminated, suggesting that commensal bacteria abundance may be a critical determinant of host lifespan. Consistent with those observations, microbial flora of aged fly gut significantly decreased axenic fly lifespan via an increase in bacterial load rather than through a change of bacterial composition. Our elaborately controlled experiments showed that the elimination of commensal microbes without detrimental side effects increased fly lifespan, and that bacterial load was a significant determinant of lifespan. Furthermore, our results indicate the presence of a deterministic connection between commensal microbes and host lifespan.
Highlights
Commensal microbes with symbiotic relationships with their hosts have been actively investigated in several fields of research in attempts to elucidate their interaction with the host
The 2G and 3G Ax flies had increased lifespans compared to that of Conv flies (Figure 1A and 1B, Supplementary Table 1; 2G Ax fly 68.52 ± 0.94 days, 14.35% increase, log-rank test, χ2 = 0.08, p = 0.77, Wilcoxon test, χ2 = 8.91, p < 0.005; 3G Ax fly 70.73 ± 0.85 days, 18.04% increase, log-rank test, χ2 = 8.20, p < 0.005, Wilcoxon test, χ2 = 18.93, p < 0.0001), suggesting that the bleaching method may have a detrimental effect on D. melanogaster, but the effect diminished over subsequent generations
To confirm whether the lifespan extension by egg bleaching is due to the absence of commensal microbes, we introduced microbes from 10-day-old Conv flies to 3day-old 3G Ax flies by using fecal transplantation
Summary
Commensal microbes with symbiotic relationships with their hosts have been actively investigated in several fields of research in attempts to elucidate their interaction with the host. Brummel et al observed that the lifespan of flies reared axenically following egg www.aging-us.com bleaching or antibiotic treatment was shorter than that of conventionally reared fly, and that effect could be recovered by exposure of the flies to microbes within 2–3 days from eclosion [11]. To clarify the reasons for these inconsistencies, we generated axenic flies using highly elaborate well-controlled methods and observed that elimination of commensal microbes without detrimental side effects increased host lifespan. To generate adult flies carrying a predetermined composition of bacteria (gnotobiotic flies), 100 μL of commensal bacterial cultures (103, 108, or 1014 CFUs) were added to sterilized food vials containing 2-day-old Ax flies. Every 2 days for 1 week, the flies were transferred to new sterile CSY food vials seeded with experiment-specific compositions of commensal bacteria. The abundances of colonized microbes were identified via CFU testing 10 days after the initial infection
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