Towards virtual physiological humans: integrating metabolism, physiology, and gut-microbiome

Science communication on a recently published paper

Precision Medicine

A milestone in precision medicine would be the ability to explore generative models that can capture the real-world complexity of human physiology. If computational models can successfully integrate physiology, metabolism, and host-microbiome data – thereby achieving personalization of predictive models of virtual physiological humans – this would be a key stepping-stone in yielding promising therapeutic targets that are both individual-specific and case-specific. Thus, the science (and art) of generating and exploring virtual physiological humans could be a boon to systems physiology and precision medicine.

Whole-body metabolic reconstructions

Towards this end, Thiele et al. recently published an intriguing paper. Thiele et al. demonstrate building and validation of sex-specific curated Whole-Body Metabolic (WBM) reconstructions. Computational models derived from such WBM reconstructions offer a novel molecular-level, anatomically and physiologically consistent, sex-specific genome-scale reconstructions of human physiology and metabolism. Thiele et al. further demonstrated that the WBM reconstructions can be ‘personalized’ via integration of quantitative physiological data with multi-omics such as metabolomics, and gut-microbiome. Thus, Thiele et al. introduce Harvey and Harvetta, the male and female WBM reconstructions, respectively. These reconstructions and the derived models and analysis enable novel assessment of, e.g., host-microbiome co-metabolism that is individual-specific and is resolved at an organ-level.


The extreme complexity of real-world metabolic modelling of host-microbiome in humans can hardly be overstated. Thiele et al. address this critical challenge via constraint-based reconstruction – their models account for the enormous diversity of microbiome-associated microbial genes that are meaningful both physiologically and is individual-specific such as in host-microbiome co-metabolism. Thus this approach allows case-specific investigation of human metabolism, such as for studying inherited metabolic diseases.


Previously the Thiele Lab , extensive metabolic modelling of metabolic and physiologically relevant pathways (curated algorithmically and manually) led to a comprehensive model that allows investigation via constraint-based reconstruction of over 80,000 pathways. Thiele et al. approached the problem into a smaller sub-problems that they have previously addressed. First – by compiling organ-specific information from previous literature and including experimental-omics data, Thiele Lab generated WBM reconstructions. Second – Thiele Lab imposed constraints the WBM reconstructions via (large-scale) physiology, dietary constraints and quantitative metabolomic data.


A key challenge that Thiele et al. addressed in this current 2020 paper is the integration of more than 80,000 biochemical reactions, that were both anatomically and physiologically consistent. These WBM reconstructions describe 26 organs and 6 blood cell types and capture whole-body organ-resolved metabolism. Importantly, these recapitulate previously known inter-organ metabolic cycles and energy use. Interestingly, WBM models can also predict biomarkers. This might, e.g., elucidate new pathways or targets that are implicated in heritable metabolic diseases.

Take-home-message and future ahead

Exploring such quantitative metabolic models could reveal new molecular insights pertaining to (co-dependence of host-microbiome) metabolism and overall human physiology and homeostasis – both in health and disease. The power of computational models is further exemplified if these allow addressing questions via novel hypothesis-testing that go beyond the scope of wet-lab experiments.

written by: Div Prasad

I’m interested in quantitative biology (at the intersection) of human genetics, machine learning, and host-microbiome interactions.

Twitter: @divyaePrasad
github: divprasad

November 2, 2019

Good Weekend morning for all!

Today’s digest is highly rich with plant and soil microbiome papers (notice a great Science paper regarding soil suppressiveness phenomena), as well as bacterial metabolism papers and more. Have a great and peaceful weekend!

Human and animal microbiome

Studying the gut virome in the metagenomic era: challenges and perspectives, Sanzhima Garmaeva, BMC Biology

Cortisol-induced signatures of stress in the fish microbiome, Tamsyn M Uren Webster, bioRxiv

Influence of pig gut microbiota on Mycoplasma hyopneumoniae susceptibility, Meera Surendran Nair, Veterinary Research

Natural variation in the contribution of microbial density to inducible immune dynamics, Derrick Jent, Molecular Ecology


The ecology and evolution of microbial metabolic strategies, Djordje Bajic & Alvaro Sanchez, Curr. Opin. In. Biotechnology

Is the enzymatic hydrolysis of soil organic phosphorus compounds limited by enzyme or substrate availability?, K.A. Jarosch ,SBB

Plant and Soil microbiome

Pathogen-induced activation of disease-suppressive functions in the endophytic root microbiome, Victor J. Carrio, Science

Drivers of the composition of active rhizosphere bacterial communities in temperate grasslands, Selma Vieira, ISME

Analysis of soil bacterial communities associated with genetically modified drought-tolerant corn, Jose G. Ibaraa ,Applid Soil Ecology

Phyllosphere of Submerged Plants in Bathing Lakes as a Reservoir of Fungi Potential Human Pathogens, Anna Biedunkiewicz, Microbial Ecology

Bacterial microbiome associated with the rhizosphere and root interior of crops in Saskatchewan, Canada, Jorge Cordero, Can. J. of Microbiology

Comparative metagenomics of two distinct biological soil crusts in the Tengger Desert, China, Jin-Yu Li , SBB

In planta bacterial multi-omics analysis illuminates regulatory principles underlying plant-pathogen interactions, Tatsuyas Nobori, bioRxiv

Air microbiome

Microbial communities in the tropical air ecosystem follow a precise diel cycle, Elena S. Gusareva, PNAS


Evaluating Bioinformatic Pipeline Performance for Forensic Microbiome Analysis, Kierra F. Kaszubinski, J. o. Forensic Sci.

October 11, 2019

Good morning everyone!

Today’s digest is full of great reviews paper, among else- from the gut microbiome to bacterial metabolic modelling. Also featured is a lovely paper regarding vaginal microbiome transplantation (with interesting translational meaning!) and a food-for-thought paper about microbiology past, present and furture (1st in the list down).

Have a great weekend and happy Jewish New year!

Food for Thought

Shift in the paradigm towards next-generation microbiology, Blaz Sterz & Luka Kronegger, FEMS Microbiology Letters

Human microbiome

** Re‐assessing microbiomes in the low‐biomass reproductive niche, Jessica L. O’Callaghan, BJOG

** Incorporating functional trade-offs into studies of the gut microbiota, Aspen T Reese, Curr. Opi. Microbiology

** Gut microbial metabolites in depression: understanding the biochemical mechanisms, Giorigia Caspani, microbial cell

** Vaginal microbiome transplantation in women with intractable bacterial vaginosis, Ahinoam Lev-Sagie, Nature Medicine

Gut microbiome diversity is associated with sleep physiology in humans, Robert P. Smith, PLOS One

Microbial Interactions in Oral Communities Mediate Emergent Biofilm Properties, P.I. Diaz, J. Dental Research

Animal microbiome

A wild microbiome improves mouse modeling of the human immune response, Sara E. Hamiltion, Lab Animal

Gut Microbiota of Migrating Wild Rabbit Fish (Siganus guttatus) Larvae Have Low Spatial and Temporal Variability, Duy Le, Microbial Ecology

Environmental microbiome

** Implications of indoor microbial ecology and evolution on antibiotic resistance, Sarah Ben Maamar, J. Exp. science & Env. Epid.

A microcosm approach highlights the response of soil mineral weathering bacterial communities to an increase of K and Mg availability, O. Nicolitch, Scientific Reports

Preceding crop and tillage system affect winter survival of wheat and the fungal communities on young wheat roots and in soil, Hanna Friberg, FEMS Microbiology Letters

Viral microbiome

A review on viral metagenomics in extreme environments, Sonia Davila-Ramos, Frontiers in Microbiology

Methods in microbiology

Multi-faceted approaches to discovering and predicting microbial nutritional interactions, Sebastian Gude, Curr. Opi. Biotechnology

Artificial neural network-assisted Fourier transform infrared spectroscopy for differentiation of Salmonella serogroups and its application on epidemiological tracing of Salmonella Bovismorbificans outbreak isolates from fresh sprouts, Helene Obereuter, FEMS Microbioogy Letters