Day 3 Round-up from the Nature Conference: Environmental Microbial Biofilms and Human Microbiomes: Drivers of Future Sustainability
Tuesday, 14 February, 2017 Theme 3: Human Micobiome: New Dimensions in Medical Microbiology
Background: Recently, human microbiome science has delivered new insights encompassing the huge microbial diversity revealed among individuals as well as among anatomic sites in a given individual.
Following the initial inescapable descriptive and correlative metagenomic studies, we now seek to consolidate information acquired by functional metagenomics to inform us on the actual role of microbiomes in human physiology, and the impact of altered microbiomes that have undergone changes in microbial composition and reduction in richness and diversity in pathology. Both bona fide in vitro and in vivo models as well as clinical studies in which the microbiome is altered are required.
David Relman, Stanford University, USA
Relman reiterated the need to focus on ecological landscapes when considering the processes that establish and maintain human microbiota throughout life. His address on Human Microbial Ecology in Health and Disease covered the nature of human-microbe interactions and underlying mechanisms, as well as determinants involved in recovery from disturbance.
Relman’s work involves investigating the microbiomes associated with pregnancy, considering the microbial community as a disease agent, rather than specific pathogens as agents of disease. Accordingly, the alternate microbial states associated with pregnancy are of interest. Comparing these to the microbiome relationships in other healthy states in women can inform on wellbeing and consequences for the foetus.
Relman advocates the need to describe the ecological adaptive landscape in individuals and consider the outcomes of a change to an alternate – less stable – ecological state. The maternal landscapes should be assessed prior to conception, as maternal microbiome transmission occurs over generations and it is important to know the state at the onset of pregnancy.
The state of the vaginal microbiome throughout pregnancy and at birth can predict the possibility of premature birth versus full term delivery. Microbiomes associated with premature birth are typically depleted in genera such as Lactobacillus, which is enriched in vaginal micorbiomes of women carrying to full term. In a longitudinal analysis of vaginal microbiomes in two cohorts, the association of interacting Lactobacillus and Gardnerella species strongly correlated with full term and pre-term births respectively.
A disturbed community in the mother is transferred to the baby during birth, and the duration of the inter-partum period in the mother correlates with risks associated with the subsequent pregnancy if a stable healthy community is not given time to restore.
Relman demonstrated the potential to predict pre-term births based on understanding the microbiome and the mechanisms that underlie stability. He suggested robust strategies for microbiome manipulation to maintain or restore health and avoid/mitigate complications. The ‘community as a pathogen’ concept needs further investigation to tease out more nuanced factors such as secondary interactions with pathogens.
Sven Pettersson, Lee Kiong Chian School of Medicine, NTU and Singapore Centre for Environmental Life Sciences Engineering, Singapore
Pettersson uses Use of Germ Free Mice as a Model System to Understand the Holobiont and the effect intimate microbial associations have on higher organisms. He describes the holobiont as the combined genomes of the host and associated microbial community, two entities that have been co-evolving for millennia and are considered to be an evolutionarily conserved functional unit. A constant cross-talk persists between the host and its microbiome. The host imparts an influence on the microbial communities and their functions through diet, exercise and circadian rhythms, while the microbes support host organs and regulate functions through the release of metabolites.
Pettersson uses a systems biology approach to the analysis several organs in the germ free (GF) mice involved in gut microbe and faecal transplant (coprophagy) assays, identifying a microbial component in diseases and disfunction associated with host tissue and organs, previously not connected to microbial activities. On closer inspection, we may find more diseases or disorders have connections to the host’s microbiome than previously imagined.
Martin Blaser, New York University School of Medicine, USA
Although adult microbiomes show considerable resilience, the microbiomes of young children are much more susceptible to change. Blaser’s presentation on Perturbing the Early Life Microbiota: Immediate Effects and Long-Term Consequences explores the ramifications for holistic wellbeing of perturbing the gut microbiome of young children, particularly with antibiotics.
The first years of a child’s life are characterised by massive changes, with the developing metabolic, immunological and cognitive functions, and now it has become evident that the gut microbiome is also in flux. The characteristic ‘adult’ microbiome does not begin to stabilise until after the age of three.
Microbiomes are vertically transmitted from mother to baby and co-evolved microbes form dynamic equilibria with the host. For post-industrialisation generations, however, the level of microbial diversity has been steadily declining in developed countries, to the extent that ~50% of faecal diversity has been lost, compared to ancestral microbiomes. This can be attributed to a number of 20th Century behavioural patterns, such as the increase in exposure to antibiotics, C-section births, bottle feeding babies, and the ‘sterilisation’ of our immediate environments.
Given the relationship between the gut microbiome and the functioning of its host, it does not seem surprising that disturbing microbial communities might have consequences for both parties. For example, the rise in obesity in modernised countries coincides with the availability of antibiotics. Animal studies suggest that although the effects of antibiotics were transient in faecal microbiomes, the induced phenotype that predisposes an individual to maximum nutrient acquisition and obesity remains (hence an increase in feeding efficiency in livestock fed therapeutic antibiotics). Thus, both therapeutic and chronic exposure to antibiotics affects the microbiome, but also impart long-term immunological effects for the host, especially in young children.
Liping Zhao, Rutgers University, Shanghai Jiao Tong University, Shanghai China
The importance of the gut microbiome to ensuring public health and wellbeing was reiterated in Zhao’s presentation on Gut Microbiome: A New Window for Human Gut Health. Humans and their associated microbiomes form a superorganism with more than a million genes working together to dictate phenotypes. We need to understand the roles of the various parties in the association, and correlate changes in the microbiome with changes in metabolites. With a proof of principle study, Zhao demonstrated the transition from association to causality for gut microbiomes and obesity. Due to interactions of this superorganism, molecular profiling (e.g. of urine metabolites) can be used to inform on physiological functions of the gut microbiome. Changes in the microbiome and metabolites can quantitatively assess and monitor health based on the whole system, and not just host genomics. Predictive pre-disease biomarkers can thus be generated and preventative measures such as specifically designed diets can be taken.
He introduced the concept of functional guilds (defined as different species working together to provide ecosystem service to the host) to overcome taxonomic ambiguities such as strain specificity, and grouping according to function. For example, a guild of microbes associated with obesity phenotypes.
During question time, he expressed the need to promote more open interactions in clinical trials, where research teams could complement each other by sharing data and analysing different components, based on their areas of interest and expertise.
Gary Wu, University
of Pennsylvania, USA
Wu’s discussion of Diet, the Gut Microbiome, and its Metabolome in Inflammatory Bowel Disease: Therapeutic Opportunities approaches host microbiome interactions from the perspective of disease and dysbiosis. In addition to the role of microbiomes in maintaining host health, they have also been implicated in numerous immune-mediated or metabolic diseases, such as inflammatory bowel disease (IBD), which have become more prevalent since industrialisation. A dysbiotic microbiota is characterised by altered community structure and loss of diversity due to environmental factors such as diet, and plays a role in disease pathogenesis. Diet has been implicated in IBD and the microbiome structure/function that affects the development of intestinal inflammation and can restructure the gut lumen. Complex three way interactions between the host, the microbiome and the environment confound therapeutic approaches to minimise/eradicate IBD symptoms. Therapies to alleviate IBD are not always successful. Exclusion diets work, but are not sustainable over the long term. Similarly, antibiotic treatments and faecal transplants are effective, but do not work consistently.
Wu outlined the Food and Resulting Microbial Metabolites (FARMM) study, designed to understand the relationship between diet, microbiomes and metabolomes to identify new therapeutic approaches. He likened the use of metabolomes as diagnostic tools to assessing the function of organs by testing urine or stool samples. Certain signature metabolomes will indicate disfunction in a particular organ, and follow-up exploratory investigations can be undertaken.
Ting Zhu, Tsinghua University, China
Zhu discussed Inhalable Microorganisms in Beijing’s Particulate Matter Pollutants and the implications for health and longevity of the city’s resident population. Beijing’s chronic air pollution is responsible for increases in respiratory diseases such as bronchitis, influenza and pneumonia. Coarse particulate matter (PM10 ≤ 10 μm) is deposited in the upper respiratory tract of humans, whereas fine particulate matter (PM2.5 ≤ 2.5 μm) makes its way into the bronchia and alveoli. Particulate pollutants comprise non-biological material such as soil, dust and fly ash, or biological components: bacteria, fungi, and viruses.
Airborne microbial metagenomic sequencing was conducted to assess the biological component of fine particulate matter suspended in a sample of Beijing’s air. Of the 1300 microbial species were identified, most were associate with soil and were non-pathogens. Many of these were, however, considered to be allergens that might result in respiratory inflammation and secondary infections.