Symbiosis: Emerging Reconceptualizations and Theories

We organize in Bordeaux, France (UTC+2), an international conference on symbiosis, with a focus on the very concept of symbiosis and the many emerging theoretical approaches to symbiosis and host-microbiome interactions. Numerous perspectives (biology, medicine, philosophy of science, science studies) and models will be considered. This conference will gather world-leading experts on symbiosis.

Speakers

• Charlotte Brives (Centre Emile Durkheim, CNRS Bordeaux, France), “Thinking through pluribiosis: the case of phage/bacteria relationships”
• Gérard Eberl (Institut Pasteur, Paris, France), “How the immune system makes the difference between pathogens and mutualists… or not”
• Hannah Kaminski (ImmunoConcept, University of Bordeaux, France), “Are damage and repair the features that microbiota and host develop to promote a stable association leading to symbiosis?”
• Sarkis Mazmanian (Caltech, USA), “The Gut Microbiome Modulates Brain Pathologies in Parkinson’s Disease”
• Margaret McFall-Ngai (Caltech, USA), “Symbiosis brings together communities of different expertise: Retaining rigor in developing this frontier”
• Spencer V. Nyholm ( University of Connecticut, USA), “Illuminating interactions between the immune system and symbiotic bacteria of the Hawaiian bobtail squid”
• Ned Ruby (Caltech, USA): Comments.

Schedule

Abstracts

Charlotte Brives, “Thinking through pluribiosis: the case of phage/bacteria relationships”

While bacteriophage viruses are most often presented as obligatory parasites, “snipers” of bacteria, phages and bacteria in fact maintain long and complex co-evolutionary relationships, difficult to reduce to parasitism.  In this presentation, I’ll focus on this complexity to develop the concept of pluribiosis. I will then show some of the implications of this concept for the use of scientific knowledge in society.

Gérard Eberl, “How the immune system makes the difference between pathogens and mutualists… or not”

It is often stated that, somehow, the immune system makes the difference between mutualists and pathogens in the microbiota, in order to avoid infection or kill harmless symbionts. Our investigations into the microbiota-host interaction rather suggest that the immune system reacts to microbes like a spring to an extensive force in order to maintain equilibrium. We find that the vigor of that spring is determined early in life during weaning, and sets the reactivity of the immune system in the long term. This phenomenon of neonatal immunological imprinting is regulated at the epigenetic level in many cells types, including hematopoietic stem cells in the bone marrow, and defines the nature and impact of microbes on the host.

Hannah Kaminski, “Are damage and repair the features that microbiota and host develop to promote a stable association leading to symbiosis?”

The immune response to the microbiota has initially been excluded from the general theory of immunity or classified as avoidance, ignorance, or tolerance. In this project, we aim to evaluate, from both a conceptual and an experimental perspective, how the microbiota and the immune system interact and contribute to a stable symbiotic relationship. Our claim will be two-fold: i) The microbiota closely resembles other bacteria considered as pathogens, leading to tissue damage, but with a lower degree of intensity; ii) this type of response, including tissue repair, contributes to symbiosis. We explore the work of Polly Matzinger, Ruslan Medzhitov, Yasmine Belkaid, and other authors to understand how the microbiota has been described as involved in tissue damage. We will also present an experimental mouse model of the establishment of the microbiota-immune system relationship during the weaning period, representing the temporal window during which the relationship between the microbiota and the immune system becomes stable, and its maintenance during adulthood.

Sarkis Mazmanian, “The Gut Microbiome Modulates Brain Pathologies in Parkinson’s Disease”
The number of people living with Parkinson’s disease (PD) is projected to double by 2040 to over 20 million worldwide. PD symptoms include severe movement disorders that are likely caused by aggregation of the neuronal protein α-synuclein (αSyn) which promotes deficits in cellular processes including autophagy, proteasome, and lysosomal function. Approximately 15% of PD incidence is attributed to a monogenic cause, suggesting a strong role for the environment in most cases. Interestingly, 70% of PD patients experience gastrointestinal (GI) symptoms that usually manifest years or decades before a PD diagnosis. αSyn aggregation may initiate in peripheral tissues such as the GI tract and eventually reach the brain. Our laboratory was the first to discover that the gut microbiome regulates PD symptoms and pathology in mouse models, and that specific bacterial species or diets impact motor deficits and neuroinflammation. We now show that αSyn overexpression in mice, a risk factor for PD, reshapes the gut microbiome and impairs its beneficial functions. Further, gut bacterial alterations induce mitochondrial dysfunction, a hallmark of human PD. Remarkably, fecal microbiota transplant (FMT) from healthy mice into a PD mouse model reverses αSyn pathology in the brain and improves motor symptoms, suggesting that genetic predisposition is not sufficient for disease and that microbiome status contributes to gene-environment interactions. We propose the bold concept that PD-associated genetics shape microbiome composition to adopt pathogenic functions, and that restoring a healthy microbial community in the gut represents potential new therapies for PD.

Margaret McFall-Ngai, “Symbiosis brings together communities of different expertise: Retaining rigor in developing this frontier”

Next-generation sequencing became widely used around 2008. This technology rendered sequencing quick and inexpensive. One major fallout of this advance was the democratizing of the use of sequencing to determine the constituents of the microbial world in any given habitat. Programs such as the EMBL Tara Oceans expeditions, the Human Microbiome Project of the US National Institutes of Health, and the Earth’s Microbiome Project of Pacific Northwest National Lab and UC San Diego, have dramatically changed our view of the biosphere. We now know that the microbial world encompasses the vast diversity of the organisms on earth and that most, if not all, animals and plants require interactions with the microbial world for a healthy ontogeny. However, the mechanistic studies of these phenomena are challenged by strong intellectual silos of the field of biology. Ironically, these silos developed with the discovery of DNA as the genetic material back in the 1950s.  The persistence of silos is reflected in university-department and funding-agency structures.  Importantly, microbiology has been most often balkanized away from the rest of biology, so macrobiologists may receive an undergraduate degree in biology with only one or a few lectures on the microbial world during their ~4 years of university education. Similarly, microbiologists are rarely trained in the biology of animals and plants. This lecture will consider how these deficiencies are affecting the quality of data emerging from studies of symbiosis and what measures might be fostered to improve rigor in the field.

Spencer Nyholm, “Illuminating interactions between the immune system and symbiotic bacteria of the Hawaiian bobtail squid”
Most animal hosts must distinguish between resident microbiota and pathogens. The Hawaiian bobtail squid, Euprymna scolopes, forms a specific association with the bioluminescent bacterium, Vibrio fischeri, that is housed in a specialized light organ. The cellular innate immune system of E. scolopes consists of one type of blood cell, the hemocyte. These cells can migrate to the light organ where they directly interact with V. fischeri. Our work demonstrates that light organ colonization influences hemocyte gene expression and protein production along with the ability of these cells to specifically bind and phagocytose V. fischeri. Live cell imaging revealed that hemocytes from wild-caught or symbiotically raised hosts bound and then subsequently released significantly more V. fischeri than non-symbiotic bacteria. This ability to avoid hemocyte binding was lost when hosts were raised without the symbiont, suggesting that light organ colonization by V. fischeri leads to changes in hemocyte development. Binding assays using V. fischeri mutants suggest that bacterial lipopolysaccharide and an outer membrane protein OmpU, mediate recognition by host hemocytes. We are currently using single-nuclei RNA sequencing and infrared spectroscopic imaging to further understand the cellular and molecular mechanisms that mediate hemocyte-bacteria interactions.
Female E. scolopes have a second symbiotic organ, the accessory nidamental gland (ANG) that contains a bacterial consortium and is also infiltrated by host hemocytes. To understand how the host maintains and regulates distinct microbiota, we used transcriptomics to identify immune-related genes that are uniquely and similarly expressed in the ANG and light organ compared to tissues without a microbiota. Peptidoglycan recognition proteins EsPGRP2 and EsPGRP3, cathepsin-Z, alkaline phosphatase, and acidic phospholipase exhibited significant upregulation in both symbiotic organs compared to other tissues. However, specific members of the antimicrobial galaxin protein family were differentially expressed in the ANG and light organ and partial peptides from two of these proteins varied in their inhibition of symbiotic and non-symbiotic bacteria. In summary, our findings identify a conserved repertoire of innate immunity genes with tailored expression patterns for regulating distinct symbiotic communities in the same host.