Detecting Reactive Oxygen Species Generation and Stem Cell Proliferation in the Drosophila Intestine

Luo, Liping; Reedy, April R.

doi:10.1007/978-1-4939-3603-8_10

Cited by 9 publications

(9 citation statements)

References 26 publications

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“…Generation of germ-free Drosophila larvae, and immunostaining and detection of cell proliferation in the intestine of third instar Drosophila larvae Germ-free Drosophila larvae were generated, and ROS-detected using the hydro Cy3 dye, using methods previously described (Luo et al, 2016). Briefly, Drosophila embryos were harvested and transferred to a cell strainer.…”

Section: Fly Strains and Bacteriamentioning

confidence: 99%

Commensal microbiota-induced redox signaling activates proliferative signals in the intestinal stem cell microenvironment

2019

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A distinct taxon of the Drosophila microbiota, Lactobacillus plantarum, is capable of stimulating the generation of reactive oxygen species (ROS) within cells, and inducing epithelial cell proliferation. Here, we show that microbial-induced ROS generation within Drosophila larval stem cell compartments exhibits a distinct spatial distribution. Lactobacilli-induced ROS is strictly excluded from defined midgut compartments that harbor adult midgut progenitor (AMP) cells, forming a functional 'ROS sheltered zone' (RSZ). The RSZ is undiscernible in germ-free larvae, but forms following monocolonization with L. plantarum. L. plantarum is a strong activator of the ROS-sensitive CncC/Nrf2 signaling pathway within enterocytes. Enterocyte-specific activation of CncC stimulated the proliferation of AMPs, which demonstrates that pro-proliferative signals are transduced from enterocytes to AMPs. Mechanistically, we show that the cytokine Upd2 is expressed in the gut following L. plantarum colonization in a CncC-dependent fashion, and may function in lactobacilli-induced AMP proliferation and intestinal tissue growth and development.

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Section: Fly Strains and Bacteriamentioning

confidence: 99%

Commensal microbiota-induced redox signaling activates proliferative signals in the intestinal stem cell microenvironment

2019

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“…Lifespan assays. For gnotobiotic experiments with Drosophila, germ-free flies were prepared as previously described (60). Briefly, Drosophila embryos were collected and transferred to a cell strainer.…”

Section: Methodsmentioning

confidence: 99%

Indoles from commensal bacteria extend healthspan

Sonowal

Swimm

Sahoo

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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147

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Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan often reduce healthspan and increase frailty. The question arises as to whether factors or mechanisms exist that uncouple these processes and extend healthspan and reduce frailty independent of lifespan. We show that indoles from commensal microbiota extend healthspan of diverse organisms, including Caenorhabditis elegans, Drosophila melanogaster, and mice, but have a negligible effect on maximal lifespan. Effects of indoles on healthspan in worms and flies depend upon the aryl hydrocarbon receptor (AHR), a conserved detector of xenobiotic small molecules. In C. elegans, indole induces a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging. Moreover, in older animals, indole induces genes associated with oogenesis and, accordingly, extends fecundity and reproductive span. Together, these data suggest that small molecules related to indole and derived from commensal microbiota act in diverse phyla via conserved molecular pathways to promote healthy aging. These data raise the possibility of developing therapeutics based on microbiota-derived indole or its derivatives to extend healthspan and reduce frailty in humans.C. elegans | aging | frailty | aryl hydrocarbon receptor | microbiota R ecent advances in health care have contributed to a significant increase in life expectancy of individuals, especially in developed countries, which predict an expansion of geriatric populations by as much as 350-fold over the next 40 y (1). However, extension of lifespan is often accompanied by increased frailty, and attendant increases in global healthcare expenditures are expected to be both massive and unsustainable (2). Such data highlight the need to develop means to extend healthspan, which is broadly defined as the length of time that an individual remains healthy and free of age-related infirmities (3, 4).Healthspan has often been convolved with lifespan, and extended healthspan has been associated with slowed onset of normal age-related changes (e.g., sarcopenia). Thus, mutations that extend lifespan might be expected to likewise extend healthspan. Recent studies in Caenorhabditis elegans indicate that, relative to wild-type animals, mutations that extend lifespan do indeed extend the period of youthfulness, in which animals are motile and resistant to bacterial infection (healthspan), but also extend the period of decrepitude or frailty, where animals are relatively immobile (5, 6) Other studies in C. elegans that take into account multiple measures of health, each normalized to maximal lifespan, indicate that mutations or conditions that extend lifespan minimally impact or ev...

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“…Previous studies have shown that the aging gut has high ROS levels (Buchon et al, 2009;Guo et al, 2014;Hochmuth et al, 2011). We used a previously established ROS sensitive dye to measure the levels of ROS in the aged gut (Luo et al, 2016). We found that there is a dramatic increase in ROS in the older fly intestine ( Figure 4C).…”

Section: The Aged Microbiota Increases Susceptibility To Enteric Infementioning

confidence: 73%

Aging-associated dysbiosis increases susceptibility to enteric viral infection inDrosophila

Sansone

Cohen

Gold

et al. 2017

Preprint

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Age is associated with increased susceptibility to enteric infections, but the molecular mechanisms are unclear. We find that aged Drosophila are more susceptible to enteric viral infections and that this increase in susceptibility is due to the aged microbiota, since depletion of the microbiota or reconstitution with a young microbiome suppressed infection. Metagenomic analysis of the aged microbiome revealed dysbiosis with an increased abundance in reactive oxygen species (ROS) producing pathways. This aged microbiota drives intestinal ROS production and we could restore immune function in old flies by reducing ROS genetically or pharmacologically. Moreover, we found that reconstitution of old flies with a cocktail of commensals, including L. fructivorans and heat-killed A. pomorum, could fully restore immunity. Altogether, these findings provide a mechanistic link between age-dependent dysbiosis and antiviral immunity and show that we can restore innate protection in aged animals, suggesting that this is a treatable and reversible state. Paraquat Control

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Detecting Reactive Oxygen Species Generation and Stem Cell Proliferation in the Drosophila Intestine

Cited by 9 publications

References 26 publications

Commensal microbiota-induced redox signaling activates proliferative signals in the intestinal stem cell microenvironment

Commensal microbiota-induced redox signaling activates proliferative signals in the intestinal stem cell microenvironment

Indoles from commensal bacteria extend healthspan

Aging-associated dysbiosis increases susceptibility to enteric viral infection inDrosophila

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