Eukaryotic Symbionts Research Articles

Distinct microbial communities supported by iron oxidation.

Microbial biostalactites and streamers commonly grow at iron seepages in abandoned mines worldwide. This study addresses the diversity and composition of these simple prokaryotic communities, which thrive in pH ranges from 2.4 to 6.6 across six different mines. Our analysis of 85 communities reveals that a pH of approximately 3.2 is a critical threshold where alpha and beta diversity change discretely. Below this pH, the average number of ASVs per sample is 2.91 times lower than above this boundary. Autotrophs, heterotrophs, and symbionts of eukaryotes originate from nearly non-overlapping species pools in the two habitat types that differ only in pH. Communities below pH 3.2 further divide into two distinct groups, differing in diversity, taxonomic, and functional composition. Both types of communities coexist within the same stalactites, likely corresponding to zones where the capillary structure of the stalactite is either perfused or clogged. These findings indicate that microbial community structure can be significantly influenced by the intricate spatial organization of the ecosystem, rather than solely by measurable environmental parameters.

Exploring the functional roles of sustainable dietary patterns on gut microbiota composition and optimal health

The aging population presents a growing global challenge, due to increased risk of age-related diseases, leading to arising burden on healthcare systems and highlighting the need for effective interventions to promote healthy aging. Emerging evidence suggests that certain dietary patterns can influence the gut microbiome favorably, potentially mitigating age-related chronic diseases and metabolic dysfunction such as diabetes, obesity, and cardiovascular diseases. Gut microbiota dynamics, initially stable in early life, are disrupted with age, impacting both prokaryotic and eukaryotic symbionts, resulting in an adaptive response in the gut microbiota defined by an increase in composition and diversity over time. In addition to environmental and genetic factors, the impact of diet has been noted as a critical factor that influences these dynamics. In this review, we propose sustainable dietary patterns like the Mediterranean, vegetarian, ketogenic, and DASH diets as a suitable panacea to counteract deleterious feeding patterns by offering nutritious and environmentally sustainable options, potentially lowering the prevalence of chronic diseases and further explores their functional roles with respect to modulating the gut microbiota composition, and their overall impact on optimal health. Keywords: Aging; healthy diet; Gut microbiota; Mediterranean Diet; Plant-based diet; dietary intervention

The metatranscriptome of resident microbiota in the gut of blue mussels, Mytilus edulis, under standard laboratory conditions

Metatranscriptomic methods involving RNA sequencing (RNA-seq) are powerful tools for evaluating the gene expression profiles of transcriptionally-active microbes that inhabit the tissues of animals. Bivalve molluscs, like all invertebrates, are holobionts and sites of interactions between host animals and both prokaryotic and eukaryotic symbionts. The present communication describes the metatranscriptomic profile of the resident microorganisms that inhabit the gut of blue mussels, Mytilus edulis, under standard laboratory conditions. Each of the eight mussels described herein were housed in isolated microcosms with routine husbandry for 14 days before their gut tissues were sampled and subjected to RNA-seq. Subsequent mRNA reads that aligned to the mussel genome were removed, and the non-host reads were annotated for function and pathway analyses. Under laboratory conditions, the resident gut microbiota expressed genes associated mostly with aerobic energy processes, with other notable contributions from metabolism and protein processing genes. At the pathway level, the most abundant complete pathways expressed in the resident gut microbial communities were related to aerobic cellular respiration, nucleotide biosynthesis, and catabolism. These data represent novel, baseline microbial gene expression information from the gut of mussels, which are crucial for future research examining the mussel holobiont and bivalve microbial ecology. Public retrieval and secondary analyses of these metatranscriptomic profiles are highly encouraged.

Complex Endosymbioses I: From Primary to Complex Plastids, Serial Endosymbiotic Events.

A considerable part of the diversity of eukaryotic phototrophs consists of algae with plastids that evolved from endosymbioses between two eukaryotes. These complex plastids are characterized by a high number of envelope membranes (more than two) and some of them contain a residual nucleus of the endosymbiotic alga called a nucleomorph. Complex plastid-bearing algae are thus chimeric cell assemblies, eukaryotic symbionts living in a eukaryotic host. In contrast, the primary plastids of the Archaeplastida (plants, green algae, red algae, and glaucophytes) possibly evolved from a single endosymbiosis with a cyanobacterium and are surrounded by two membranes. Complex plastids have been acquired several times by unrelated groups of eukaryotic heterotrophic hosts, suggesting that complex plastids are somewhat easier to obtain than primary plastids. Evidence suggests that complex plastids arose twice independently in the green lineage (euglenophytes and chlorarachniophytes) through secondary endosymbiosis, and four times in the red lineage, first through secondary endosymbiosis in cryptophytes, then by higher-order events in stramenopiles, alveolates, and haptophytes. Engulfment of primary and complex plastid-containing algae by eukaryotic hosts (secondary, tertiary, and higher-order endosymbioses) is also responsible for numerous plastid replacements in dinoflagellates. Plastid endosymbiosis is accompanied by massive gene transfer from the endosymbiont to the host nucleus and cell adaptation of both endosymbiotic partners, which is related to the trophic switch to phototrophy and loss of autonomy of the endosymbiont. Such a process is essential for the metabolic integration and division control of the endosymbiont in the host. Although photosynthesis is the main advantage of acquiring plastids, loss of photosynthesis often occurs in algae with complex plastids. This chapter summarizes the essential knowledge of the acquisition, evolution, and function of complex plastids.

The Reemergence of Phycopathology: When Algal Biology Meets Ecology and Biosecurity.

Viruses, bacteria, and eukaryotic symbionts interact with algae in a variety of ways to cause disease complexes, often shaping marine and freshwater ecosystems. The advent of phyconomy (a.k.a. seaweed agronomy) represents a need for a greater understanding of algal disease interactions, where underestimated cryptic diversity and lack of phycopathological basis are prospective constraints for algal domestication. Here, we highlight the limited yet increasing knowledge of algal pathogen biodiversity and the ecological interaction with their algal hosts. Finally, we discuss how ecology and cultivation experience contribute to and reinforce aquaculture practice, with the potential to reshape biosecurity policies of seaweed cultivation worldwide.

The terrestrial isopod symbiont ‘Candidatus Hepatincola porcellionum’ is a potential nutrient scavenger related to Holosporales symbionts of protists

The order Holosporales (Alphaproteobacteria) encompasses obligate intracellular bacterial symbionts of diverse Eukaryotes. These bacteria have highly streamlined genomes and can have negative fitness effects on the host. Herein, we present a comparative analysis of the first genome sequences of ‘Ca. Hepatincola porcellionum’, a facultative symbiont occurring extracellularly in the midgut glands of terrestrial isopods. Using a combination of long-read and short-read sequencing, we obtained the complete circular genomes of two Hepatincola strains and an additional metagenome-assembled draft genome. Phylogenomic analysis validated its phylogenetic position as an early-branching family-level clade relative to all other established Holosporales families associated with protists. A 16S rRNA gene survey revealed that this new family encompasses diverse bacteria associated with both marine and terrestrial host species, which expands the host range of Holosporales bacteria from protists to several phyla of the Ecdysozoa (Arthropoda and Priapulida). Hepatincola has a highly streamlined genome with reduced metabolic and biosynthetic capacities as well as a large repertoire of transmembrane transporters. This suggests that this symbiont is rather a nutrient scavenger than a nutrient provider for the host, likely benefitting from a nutrient-rich environment to import all necessary metabolites and precursors. Hepatincola further possesses a different set of bacterial secretion systems compared to protist-associated Holosporales, suggesting different host-symbiont interactions depending on the host organism.

Multiple sclerosis and the microbiota: Progress in understanding the contribution of the gut microbiome to disease.

Multiple sclerosis (MS), a neurological autoimmune disorder, has recently been linked to neuro-inflammatory influences from the gut. In this review, we address the idea that evolutionary mismatches could affect the pathogenesis of MS via the gut microbiota. The evolution of symbiosis as well as the recent introduction of evolutionary mismatches is considered, and evidence regarding the impact of diet on the MS-associated microbiota is evaluated. Distinctive microbial community compositions associated with the gut microbiota of MS patients are difficult to identify, and substantial study-to-study variation and even larger variations between individual profiles of MS patients are observed. Furthermore, although some dietary changes impact the progression of MS, MS-associated features of microbiota were found to be not necessarily associated with diet per se. In addition, immune function in MS patients potentially drives changes in microbial composition directly, in at least some individuals. Finally, assessment of evolutionary histories of animals with their gut symbionts suggests that the impact of evolutionary mismatch on the microbiota is less concerning than mismatches affecting helminths and protists. These observations suggest that the benefits of an anti-inflammatory diet for patients with MS may not be mediated by the microbiota per se. Furthermore, any alteration of the microbiota found in association with MS may be an effect rather than a cause. This conclusion is consistent with other studies indicating that a loss of complex eukaryotic symbionts, including helminths and protists, is a pivotal evolutionary mismatch that potentiates the increased prevalence of autoimmunity within a population.

Evolutionary genomics of APSE: a tailed phage that lysogenically converts the bacterium Hamiltonella defensa into a heritable protective symbiont of aphids

BackgroundMost phages infect free-living bacteria but a few have been identified that infect heritable symbionts of insects or other eukaryotes. Heritable symbionts are usually specialized and isolated from other bacteria with little known about the origins of associated phages. Hamiltonella defensa is a heritable bacterial symbiont of aphids that is usually infected by a tailed, double-stranded DNA phage named APSE.MethodsWe conducted comparative genomic and phylogenetic studies to determine how APSE is related to other phages and prophages.ResultsEach APSE genome was organized into four modules and two predicted functional units. Gene content and order were near-fully conserved in modules 1 and 2, which encode predicted DNA metabolism genes, and module 4, which encodes predicted virion assembly genes. Gene content of module 3, which contains predicted toxin, holin and lysozyme genes differed among haplotypes. Comparisons to other sequenced phages suggested APSE genomes are mosaics with modules 1 and 2 sharing similarities with Bordetella-Bcep-Xylostella fastidiosa-like podoviruses, module 4 sharing similarities with P22-like podoviruses, and module 3 sharing no similarities with known phages. Comparisons to other sequenced bacterial genomes identified APSE-like elements in other heritable insect symbionts (Arsenophonus spp.) and enteric bacteria in the family Morganellaceae.ConclusionsAPSEs are most closely related to phage elements in the genus Arsenophonus and other bacteria in the Morganellaceae.

Improved high throughput protocol for targeting eukaryotic symbionts in metazoan and eDNA samples.

Eukaryote symbionts of animals are major drivers of ecosystems not only because of their diversity and host interactions from variable pathogenicity but also through different key roles such as commensalism and to different types of interdependence. However, molecular investigations of metazoan eukaryomes require minimising coamplification of homologous host genes. In this study we (1) identified a previously published “antimetazoan” reverse primer to theoretically enable amplification of a wider range of microeukaryotic symbionts, including more evolutionarily divergent sequence types, (2) evaluated in silico several antimetazoan primer combinations, and (3) optimised the application of the best performing primer pair for high throughput sequencing (HTS) by comparing one‐step and two‐step PCR amplification approaches, testing different annealing temperatures and evaluating the taxonomic profiles produced by HTS and data analysis. The primer combination 574*F – UNonMet_DB tested in silico showed the largest diversity of nonmetazoan sequence types in the SILVA database and was also the shortest available primer combination for broadly‐targeting antimetazoan amplification across the 18S rRNA gene V4 region. We demonstrate that the one‐step PCR approach used for library preparation produces significantly lower proportions of metazoan reads, and a more comprehensive coverage of host‐associated microeukaryote reads than the two‐step approach. Using higher PCR annealing temperatures further increased the proportion of nonmetazoan reads in all sample types tested. The resulting V4 region amplicons were taxonomically informative even when only the forward read is analysed. This region also revealed a diversity of known and putatively parasitic lineages and a wider diversity of host‐associated eukaryotes.

The fungus Leptosphaerulina persists in Anopheles gambiae and induces melanization.

Anopheles mosquitoes are colonized by diverse microorganisms that may impact on host biology and vectorial capacity. Eukaryotic symbionts such as fungi have been isolated from Anopheles, but whether they are stably associated with mosquitoes and transmitted transstadially across mosquito life stages or to subsequent generations remains largely unexplored. Here, we show that a Leptosphaerulina sp. fungus isolated from the midgut of An. gambiae can be stably associated with An. gambiae host and that it imposes low fitness cost when re-introduced through co-feeding. This fungus is transstadially transmitted across An. gambiae developmental stages and to their progeny. It is present in field-caught larvae and adult mosquitoes at moderate levels across geographical regions. We observed that Leptosphaerulina sp. induces a distinctive melanotic phenotype across the developmental stages of mosquito. As a eukaryotic symbiont that is stably associated with An. gambiae Leptosphaerulina sp. can be explored for paratransgenesis.

Behavior of eukaryotic symbionts in large benthic foraminifers Calcarina gaudichaudii and Baculogypsina sphaerulata under exposure to wastewater

Large benthic foraminifers (LBFs) are significant contributors to coral island formation in the Pacific Ocean. In recent years, the population of LBFs has decreased because of the increase in anthropogenic influences, such as wastewater (WW) discharge. To implement efficient mitigation measures, pollution tolerance in LBFs should be understood. However, the effects of WW on LBFs and their symbionts have not yet been demonstrated. This study examined the changes in the photosynthetic efficiency (Y[II]) of Calcarina gaudichaudii and Baculogypsina sphaerulata in response to WW by using a pulse-amplitude-modulation fluorometer. These LBFs were exposed to WW with different dilution levels for 22 days. The Y(II) values of the LBFs were found to deteriorate within 1–2 days. However, the Y(II) values both deteriorated and were enhanced in the experiments, thus indicating that WW contains both harmful and beneficial components. Baculogypsina sphaerulata showed an earlier response and greater sensitivity to WW and a higher epibiont infestation than C. gaudichaudii. This result can be attributed to the differences in the physiological and morphological responses of distinct LBFs. A sequencing analysis of 18S rDNA confirmed that the dominant eukaryotic symbionts in the two LBFs studied were Ochrophyta and Labyrinthulomycetes. These eukaryotic symbionts were released and attached as epibionts onto LBFs that were exposed to WW, thus leading to an increase in inactive LBFs. The Shannon–Weaver and Simpson diversity indices revealed that eukaryotic symbiont communities decreased in biodiversity after exposure to WW because of the abundance of algal symbionts. On the basis of these results, we conclude that WW, even with 10,000 × dilution, causes a decrease in active LBF populations owing to the release of eukaryotic symbionts, the decrease in biodiversity, and the infestation of epibionts even though Y(II) is temporarily enhanced. These responses are more significant in B. sphaerulata than in C. gaudichaudii.

Origin of Mutualism Between Termites and Flagellated Gut Protists: Transition From Horizontal to Vertical Transmission

Lower termites, as well as their sister group, the subsocial wood-feeding cockroach Cryptocercus, rely on flagellated eukaryotic symbionts in the hindgut to cooperatively digest their wood diet. In Cryptocercus these flagellates undergo encystment cycles tightly coordinated with the molting cycle of their host, yet the resultant cysts play no demonstrated role in their transmission to neonates; the trophozoite stage of the flagellates is passed directly from parents to offspring via hindgut fluids (proctodeal trophallaxis). This pattern suggests that encystment is a vestige from a gregarious cockroach ancestor, when the flagellates had a functional, two-stage life cycle and the cysts were horizontally transmitted among hosts via coprophagy. The strong integration between flagellate encystment cycles and host developmental physiology in Cryptocercus indicates that the relationship of the flagellates with their proposed gregarious cockroach ancestor was not commensal, but parasitic, with flagellates likely obtaining benefits by taking advantage of host gut metabolites and ingested plant debris. When vertical transmission evolved the parasites were ‘captured’, and their fitness became inescapably embedded in the fitness of their host. The vertical transmission of gut flagellates and the origin of host subsociality via proctodeal trophallaxis can be considered two sides of the same coin. From the host point of view proctodeal trophallaxis marks the origination of parental care by provisioning neonates with nourishment, metabolites and beneficial microbiota. From the flagellate point of view, proctodeal trophallaxis was a shift from horizontal to vertical transmission, pushing them from the parasitic to the mutualistic end of the symbiotic spectrum, arguably making this host behavioral change the most critical juncture in the evolutionary trajectory of the termite lineage.

The Significance of Microbial Symbionts in Ecosystem Processes.

It is increasingly accepted that the microbial symbionts of eukaryotes can have profound effects on host ecology and evolution. However, the relative contribution that they make directly to ecosystem processes, like energy and nutrient flows, is less explicitly acknowledged and, in many cases, only poorly constrained. Here, I explore the idea that, in some habitats, host-associated microbes may have an outsized role in ecosystem processes relative to functionally equivalent free-living microbes due to key aspects of the physiology, ecology, and evolution of symbiotic interactions. My research quantifying symbiont metabolism has shown that microbial symbionts have the potential to make a substantial impact on carbon and sulfur cycling. It is my perspective that direct measurement of symbiont activity and comparison to free-living counterparts will expand our understanding of the significance of microbial symbioses and, more broadly, the role of microbial processes in ecosystems.

The state of art and prospects for development of symbiogenetics

The modern stage of development of symbiogenetics, a biological discipline that addresses the formation of super-species genetic systems, is associated with the study of molecular mechanisms and environmental consequences of combining the hereditary factors of prokaryotes and eukaryotes into functionally integrated symbiogenomes, which, as partners lose their ability to autonomous existence, are transformed into structurally integrated hologenomes. The loss by intracellular symbionts of eukaryotes of their genetic individuality, determined by the ability to independently maintain and express the genome, representing a key step in symbiogenesis which results in the transformation of bacteria into cellular organelles. Genetic reconstruction of symbiogenesis provides the broad prospects for its artificial reproduction aimed at the synthesis of new organisms and biosystems possessing the predetermined sets of practically significant features.

Unprecedented Symbiont Eukaryote Diversity Is Governed by Internal Trophic Webs in a Wild Non-Human Primate

Research on host-associated microbiomes has highlighted major divisions between the role of eukaryotes in free-living and symbiont systems. These trends call into question the relevance of macroecological processes to host-associated systems and the relative importance of parasitism, commensalism, and mutualism as evolutionary patterns across the domains of life. However, it is unclear as to whether these apparent differences reflect biological realities or methodologies in community characterization: free-living eukaryotes tend to be characterized using metabarcoding whereas symbiont eukaryotes are typically characterized with microscopy. Here, we utilize an Illumina high-throughput metabarcoding approach to characterize the diversity and dynamics of eukaryotic symbiont communities in the feces of a wild non-human primate, Macaca fascicularis, revealing functionally and taxonomically diverse communities of eukaryotes hitherto unreported from any vertebrate. Importantly, community assembly was consistent with top-down and bottom-up trophic food web dynamics, highlighting the applicability of macroecological principles to these communities. Ultimately, our findings highlight vertebrate-associated symbiont communities of the gut that are much more similar to free-living systems than previously realized. Additionally, our results support a role for symbiosis as a major recurrent life strategy among eukaryotes and highlight the potential for vertebrates to host vast reservoirs of unexplored eukaryotic diversity.

Mosquito vector-associated microbiota: Metabarcoding bacteria and eukaryotic symbionts across habitat types in Thailand endemic for dengue and other arthropod-borne diseases.

Vector‐borne diseases are a major health burden, yet factors affecting their spread are only partially understood. For example, microbial symbionts can impact mosquito reproduction, survival, and vectorial capacity, and hence affect disease transmission. Nonetheless, current knowledge of mosquito‐associated microbial communities is limited. To characterize the bacterial and eukaryotic microbial communities of multiple vector species collected from different habitat types in disease endemic areas, we employed next‐generation 454 pyrosequencing of 16S and 18S rRNA amplicon libraries, also known as metabarcoding. We investigated pooled whole adult mosquitoes of three medically important vectors, Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus, collected from different habitats across central Thailand where we previously characterized mosquito diversity. Our results indicate that diversity within the mosquito microbiota is low, with the majority of microbes assigned to one or a few taxa. Two of the most common eukaryotic and bacterial genera recovered (Ascogregarina and Wolbachia, respectively) are known mosquito endosymbionts with potentially parasitic and long evolutionary relationships with their hosts. Patterns of microbial composition and diversity appeared to differ by both vector species and habitat for a given species, although high variability between samples suggests a strong stochastic element to microbiota assembly. In general, our findings suggest that multiple factors, such as habitat condition and mosquito species identity, may influence overall microbial community composition, and thus provide a basis for further investigations into the interactions between vectors, their microbial communities, and human‐impacted landscapes that may ultimately affect vector‐borne disease risk.

Transcriptomic Resilience of the Montipora digitata Holobiont to Low pH

Ocean acidification is considered as one of the major threats for coral reefs at a global scale. Marine calcifying organisms, including stony corals, are expected to be the most affected by the predicted decrease of the surface water pH at the end of the century. The severity of the impacts on coral reefs remains as a matter of controversy. Although previous studies have explored the physiological response of stony corals to changes in pH, the response of the holobiont (i.e., the coral itself plus its symbionts) remains largely unexplored. In the present study, we assessed the changes in overall gene expression of the coral Montipora digitata and its microalgal symbionts after a short (3 days) and a longer (42 days) exposure to low pH (7.6). The short-term exposure to low pH caused small differences in the expression level of the host, impacting mostly genes associated with stress response in other scleractinians. Longer exposure to low pH resulted in no significant changes in gene expression of treated vs. control coral hosts. Gene expression in the eukaryotic symbionts remained unaltered at both exposure times. Our findings suggest resilience, in terms of gene expression, of the M. digitata holobiont to pH decrease, as well as capability to acclimatize to extended periods of exposure to low pH.

Genotype specificity among hosts, pathogens, and beneficial microbes influences the strength of symbiont-mediated protection.

The microbial symbionts of eukaryotes influence disease resistance in many host‐parasite systems. Symbionts show substantial variation in both genotype and phenotype, but it is unclear how natural selection maintains this variation. It is also unknown whether variable symbiont genotypes show specificity with the genotypes of hosts or parasites in natural populations. Genotype by genotype interactions are a necessary condition for coevolution between interacting species. Uncovering the patterns of genetic specificity among hosts, symbionts, and parasites is therefore critical for determining the role that symbionts play in host‐parasite coevolution. Here, we show that the strength of protection conferred against a fungal pathogen by a vertically transmitted symbiont of an aphid is influenced by both host‐symbiont and symbiont‐pathogen genotype by genotype interactions. Further, we show that certain symbiont phylogenetic clades have evolved to provide stronger protection against particular pathogen genotypes. However, we found no evidence of reciprocal adaptation of co‐occurring host and symbiont lineages. Our results suggest that genetic variation among symbiont strains may be maintained by antagonistic coevolution with their host and/or their host's parasites.

The symbiotic life of Symbiodinium in the open ocean within a new species of calcifying ciliate (Tiarina sp.).

Symbiotic partnerships between heterotrophic hosts and intracellular microalgae are common in tropical and subtropical oligotrophic waters of benthic and pelagic marine habitats. The iconic example is the photosynthetic dinoflagellate genus Symbiodinium that establishes mutualistic symbioses with a wide diversity of benthic hosts, sustaining highly biodiverse reef ecosystems worldwide. Paradoxically, although various species of photosynthetic dinoflagellates are prevalent eukaryotic symbionts in pelagic waters, Symbiodinium has not yet been reported in symbiosis within oceanic plankton, despite its high propensity for the symbiotic lifestyle. Here we report a new pelagic photosymbiosis between a calcifying ciliate host and the microalga Symbiodinium in surface ocean waters. Confocal and scanning electron microscopy, together with an 18S rDNA-based phylogeny, showed that the host is a new ciliate species closely related to Tiarina fusus (Colepidae). Phylogenetic analyses of the endosymbionts based on the 28S rDNA gene revealed multiple novel closely related Symbiodinium clade A genotypes. A haplotype network using the high-resolution internal transcribed spacer-2 marker showed that these genotypes form eight divergent, biogeographically structured, subclade types that do not seem to associate with any benthic hosts. Ecological analyses using the Tara Oceans metabarcoding data set (V9 region of the 18S rDNA) and contextual oceanographic parameters showed a global distribution of the symbiotic partnership in nutrient-poor surface waters. The discovery of the symbiotic life of Symbiodinium in the open ocean provides new insights into the ecology and evolution of this pivotal microalga and raises new hypotheses about coastal pelagic connectivity.

Abstract PL01-02: Influence of the microbiota on cellular proliferation and survival

Abstract The resident prokaryotic microbiota of the mammalian intestine influences diverse homeostatic functions of the gut, including maintenance of barrier function, modulation of immune responses, as well as energy and nutrient extraction. Additionally, through studies of germ free mice, it has become apparent that commensal prokaryotic organisms are involved in the regulation of growth and survival in the intestinal epithelia, and thus may play fundamental roles in the pathogenesis of colon cancers. However, the molecular mechanisms of growth control by prokaryotes in the gut are largely unknown. It is increasingly recognized that physiologically generated reactive oxygen species (ROS) function as signaling secondary messengers that influence cellular proliferation and differentiation in a variety of biological systems. We have shown that commensal bacteria, particularly members of the genus Lactobacillus, can activate NADPH oxidase 1 (Nox1)-dependent ROS generation and modulate multiple cellular pathways, including NF-kB, ERK-MAPK and focal adhesion kinase, that are involved in control of epithelial cellular survival, proliferation, and migration. ROS inducing commensal bacteria can rapidly stimulate consequent cellular proliferation in intestinal stem cells upon initial ingestion into the murine or Drosophila intestine, illustrating the highly conserved nature of this host microbe interaction. Additionally, a well-studied and evolutionarily highly conserved system for transducing exogenous stimuli into eukaryotic host tissues is Nrf2 signaling. Nrf2 pathway activation upregulates a regulon of genes including those involved in xenobiotic and ROS detoxification, as well as pro-restitutive function. This pathway has attracted considerable attention because small molecule inducers of Nrf2 have cytoprotective and growth modulatory effects. We show cellular ROS generated in response to contact with lactobacilli have cytoprotective effects in the intestinal epithelium through the activation of Nrf2 responsive cytoprotective genes. These data suggest that the Nrf2 pathway, and perhaps other highly conserved pathways that respond to environmental alterations, have been adapted as signaling conduits between eukaryotic host and prokaryotic symbiont, and highlight the role the microbiota plays in eukaryotic cytoprotective pathways. Characterization of these pathways may have significant implications in the delineation of a eubiotic microbiota, and in the identification of probiotic microbes with potential to influence epithelial growth and survival. Citation Format: Andrew Scott Neish. Influence of the microbiota on cellular proliferation and survival. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr PL01-02.