Probabilistic Invasion Underlies Natural Gut Microbiome Stability

Abstract

SUMMARY Species compositions of gut microbiomes impact host health [1–3], but the processes determining these compositions are largely unknown. An unexplained observation is that gut species composition varies widely between individuals but is largely stable over time within individuals [4, 5]. Stochastic factors during establishment may drive these alternative stable states (colonized versus non-colonized) [6, 7], which can influence susceptibility to pathogens such as Clostridium difficile. Here we sought to quantify and model the dose-response, dynamics, and stability of bacterial colonization in the fruit fly (Drosophila melanogaster) gut. Our precise, high-throughput technique revealed stable between-host variation in colonization when individual germ-free flies were fed their own natural commensals (including the probiotic Lactobacillus plantarum). Some flies were colonized while others remained germ-free even at extremely high bacterial doses. Thus, alternative stable states of colonization exist even in this low complexity model of host-microbe interactions. These alternative states are driven by a fundamental asymmetry between the inoculum population and the stably colonized population that is mediated by spatial localization and a population bottleneck, which makes stochastic effects important by lowering the effective population size. Prior colonization with other bacteria reduced the chances of subsequent colonization, thus increasing the stability of higher diversity guts. Therefore, stable gut diversity may be driven by inherently stochastic processes, which has important implications for combatting infectious diseases and for stably establishing probiotics in the gut.

Chronic ethanol ingestion impairs Drosophila melanogaster health in a microbiome-dependent manner

“…This is comparable to previous studies of D. melanogaster (Blum et al 2013;Obadia et al 2017). While mean total bacterial abundance decreased 10 fold from 0% to 2.5% ethanol, we found (contrary to our expectations) that total load was still relatively constant from 2.5% up until the highest ethanol treatment (Figure 3).…”

“…On days 14, 21, 28, and 31, one to three individual flies from each replication and treatment were externally sterilized, homogenized, serially diluted, and plated onto MRS media (Obadia et al 2017). For the 12.5% and 15% ethanol treatments, we did not sample flies on days 31, and 28 and 31, respectively, because of fly death before the end of the experiment.…”

“…How these Drosophila-bacteria interactions affect the ecology and evolution of wild populations of flies is unknown: perhaps the transient nature of intestinal bacteria precludes a significant role of the microbiome in shaping Drosophila biology (Blum et al 2013;Broderick et al 2014)? However, because recent work has shown that certain strains of wild-collected bacteria stably colonize the D. melanogaster intestinal tract (Obadia et al 2017;Téfit et al 2017), there is the possibility of tight host-microbe associations that can significantly influence fitness under natural conditions.…”

Common structuring principles of the Drosophila melanogaster microbiome on a continental scale and between host and substrate

“…melanogaster to shape its associated microbiome might be limited (Blum et al ., ; Wong et al ., ). Instead, probabilistic processes contribute to gut colonization (Obadia et al ., ) and community structure in natural populations can be explained to a large extent by neutral ecological mechanisms (Adair et al ., ). As in mammals and other organisms, environmental factors, such as the time of collection (Adair et al ., ; Behrman et al ., ) or diet (Chandler et al ., ; Staubach et al ., ; Erkosar et al ., ; Wang and Staubach, ) have a strong effect on the Drosophila microbiome.…”

Fly foregut and transmission of microbes

“…In today's atmosphere of emerging infectious diseases and, the effect global warming will have on both vectors (i.e. flies- Nichols, 2005) and microbial pathogens, researchers, clinicians, and physicians must be aware of how these pathogens are obtained from the environment, how they remain/persist (Ma and Leulier, 2018;Obadia et al, 2017) within the vector/host, how they are transmitted to either our food products, our foods or to various hosts, and finally, how they might affect various tissues or organs of the host. Historically, and even recently, most pathogen research concerning adult dipterans has focused on the midgut (Lehane and Billingsley, 1996) and hindgut (Christofi and Apidianakis, 2013), ignoring the foregut.…”