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

Abstract

The microbiome can modulate the interaction between animals and their environment. In particular, intestinal microbes play a strong role in shaping how animals respond to their diets, and especially dietary toxins. In this study, we investigated how the microbiome affects the interaction between the fruit fly Drosophila melanogaster and ingested ethanol. D. melanogaster naturally feeds on fermenting fruits and therefore commonly ingests ethanol. This dietary ethanol is generally considered to be a toxin, but its effect on adult fly fitness has yet to be shown. We found that the reproductive output of bacterially-colonized flies remains high with low amounts of dietary ethanol, while that of bacteria-free flies decreases precipitously after ethanol ingestion. This shows that bacteria protect D. melanogaster from the damaging effects of ingested ethanol, which has important implications for fitness under natural conditions. We also observed that bacterial colonization and ethanol both negatively affect fly lifespan. In particular, bacteria play a dominant role on fly lifespan and therefore the negative effects of ethanol are only observed in bacteria-free flies. We next asked how the bacterial microbiota changes in response to dietary ethanol. Contrary to our expectations, we found that total bacterial abundance stays relatively constant with increasing ethanol. In vivo survival of bacteria was well above the in vitro toxic dose of ethanol, demonstrating that the host is shielding the microbiome from the negative effects of ethanol. Next, we investigated several aspects of host physiology that may underlie bacterially-modulated fitness changes. We found that regardless of bacterial colonization, ethanol ingestion decreases the prevalence of intestinal barrier failure and increases fly body fat content, suggesting these mechanisms are not directly responsible for bacteria-dependent fitness differences. Finally, measurements of dietary ethanol content suggest that bacterial metabolism can only partially explain the observed fitness effects. Overall, we found significant bacteria-byethanol interactions on D. melanogaster and that bacteria ameliorate the negative effects of ethanol on host fecundity. Because of the central role of ethanol in the ecology of D. melanogaster, these results have important implications for our understanding of fruit fly natural history. More generally, they underscore the importance of the microbiome in shaping an animal's interaction with its environment.

The Microbiota-Gut-Brain Axis

“…The impact of substance abuse on the microbiota has been most extensively studied in alcohol abuse. Research has linked alterations in gut microbiota during alcohol consumption to increased intestinal permeability and hepatic inflammation (168,227,273,914,925,1086,1087,1641), but a reduced gut microbiome can also protect from alcohol-induced neuroinflammation resulting in the alteration of intestinal and brain inflammasome expression (926). Preclinical supplementation with L. rhamnosus GG has been shown to lessen the severity of alcoholic hepatitis (227).…”

Reports from a Healthy Community: the 7th Conference on Beneficial Microbes

“…Chandler observed that dietary ethanol leads to a dose-dependent decrease of life span in germfree flies, while conventionally reared flies have stable life spans at low and moderate ethanol concentrations. Chandler found that ethanol also alters some immune markers but only in conventionally reared flies (31), which may parallel findings in humans that ethanol-induced inflammation and alcoholic liver disease are influenced by the microbiome. Reed Stubbendieck (University of Wisconsin-Madison, Madison, WI) presented "Bacterial Competition Mediated by Siderophore Production among the Human Nasal Microbiota."…”