Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality

Abstract

Summary Alterations in the composition of the intestinal microbiota have been correlated with aging and measures of frailty in the elderly. However, the relationships between microbial dynamics, age-related changes in intestinal physiology and organismal health remain poorly understood. Here, we show that dysbiosis of the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, is tightly linked to age-onset intestinal barrier dysfunction in Drosophila. Indeed, alterations in the microbiota precede and predict the onset of intestinal barrier dysfunction in aged flies. Changes in microbial composition occurring prior to intestinal barrier dysfunction contribute to changes in excretory function and immune gene activation in the aging intestine. In addition, we show that a distinct shift in microbiota composition follows intestinal barrier dysfunction leading to systemic immune activation and organismal death. Our results indicate that alterations in microbiota dynamics could contribute to and also predict varying rates of health decline during aging in mammals.

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

“…Bacterially-colonized flies showed a shorter lifespan than germ-free flies (Pairwise t-test, corrected P = 1.0 x 10 -12 ), in agreement with previous studies (Ridley et al 2012;Clark et al 2015;Steinfeld 1927). However, the shorter lifespan in bacterially-colonized flies was robust to dietary ethanol, with no significant ethanol-linked decrease in lifespan observed except at very high (and unnatural) levels of 12.5% ethanol or greater ( Figure 2; Table 2; Data for individual flies is shown in Figures S2; Lifespan curves are shown in Figure S3).…”

Friend, foe or food? Recognition and the role of antimicrobial peptides in gut immunity and Drosophila –microbe interactions

“…In the absence of microbiota, stem cell proliferation and immune and homeostatic gene expression is more similar to young flies, and axenic flies live longer than their conventionally reared counter parts [42,63,98]. One paradox is that as flies age they express higher levels of AMPs, which is attributed to the loss of negative regulators [42,64] and epithelial barrier dysfunction linked to microbiota dysbiosis [96,99], yet are colonized with a higher density of bacteria. One explanation is that the higher levels of antimicrobial peptides select for resistant bacteria that are capable of persisting in the gut [35].…”

“…Comparison between wild-type and Imd mutant flies has shown that the gut immune response is an important regulator of microbiota composition and density, as flies lacking Imd, and thus a functional AMP response, have higher bacterial loads, altered microbiome composition, and lack spatial organization of the microbiota in the gut [42]. As flies age, the loss of normal immune and homeostatic regulation and aberrant gut microbiota can exacerbate these effects [63,64,96]. Older flies are associated with higher densities of gut bacteria, but also express higher levels of AMPs.…”

Gut microbiota, healthy ageing and age-associated intestinal diseases: Drosphila intestine as a good model

“…Likewise, dysbiosis of the intestinal microfora, characterized by an expansion of the Gammaproteobacteria, is strongly correlated to intestinal barrier dysfunction with ageing in Drosophila. Changes in microbial composition occurring prior to or following intestinal barrier dysfunction contribute to alteration of the immune responses in the ageing flies (13). Altogether, alterations in the composition and quantity of microbiota can contribute to and also predict various rates of health decline during ageing in mammals.…”

“…Altogether, alterations in the composition and quantity of microbiota can contribute to and also predict various rates of health decline during ageing in mammals. In this regard, establishing a casual link between dybiosis and dysplasia is critical in studying ageing-associated diseases and intestinal diseases, including inflammatory bowel disease, autoimmune diseases, allergic diseases, diabetes, obesity and cancer (13)(14)(15).…”