How Are You – and How’s Your Microbiome?
Exploration of the human body’s ‘second genome’ could transform health and medicine – and robust analytical methodologies are key.
Microbes are everywhere. They are present in our gut, on our skin, in our oral cavity – and we may even carry a ‘bacterial plume’ around us. Our microbiota (the term used to describe the plethora of species present in an ecosystem) does more than just reside in our body, responding to changes within as we mature; recent studies have shown that the compositional balance of the microbiota and its expressed genes – the ‘microbiome’ – has a significant effect on health and well-being of the individual. Many pathological conditions, including allergies, inflammatory bowel disease, immunological disorders, type 2 diabetes, obesity, cardiovascular disease as well as mental health conditions, are influenced by the microbiome. Researchers describe the microbiome as the ‘second genome’ of the body – and there is potential to manipulate it to address disease states.
Both academic and clinical researchers are keenly studying the microbiome and its interaction with the environment, using techniques such as metagenomics, meta-transcriptomics and metaproteomics. Metagenomics – which studies the taxonomy of the microbiota (genera and species) helps in understanding the composition of microbiome. More importantly, meta-transcriptomic (RNA expression) and metaproteomic (protein expression) studies yield an insight into genes expressed by the microbiota as a community. It offers a much deeper understanding of how the microbiome interacts within the host environment – and affects the host. Though nucleic acid-based metagenomics and meta-transcriptomics are more sensitive technologies, metaproteomics offers insight into enzymes responsible for catalyzing reactions that affect the host. The metaproteome changes of the community (estimated by the functional categories of proteins expressed) offer a better indication as to how microbiota react to a change in the environment (for example, a disease) than estimation of the taxonomic composition of the community, which may remain unaffected.
The most interesting insights on how microbiomes affect our bodies in response to dietary habits have come from studies on malnourished or obese twins and on “germ-free” mice. When the gut microbiota of germ-free mice were replaced with microbiota from malnourished children and fed a poor diet, the mice lost weight and exhibited malnourished phenotypes (1). In another study, when the gut microbiota from obese person were introduced into the germ-free mice, they gained weight. And when the microbiota of obese mice were replaced with those from lean subjects, they maintained a normal weight if provided with a healthy, fat-reduced diet (2). On the other hand, studies on the effect of antibiotics on the human microbiome during the treatment of infections show that microbiota from even mature adults can change profoundly after antibiotic treatment (3). In addition to the increased threat of antibiotic-resistance caused by overuse, antibiotics can also have drastic side effects on the normal gut microflora.
To restore normal healthy flora, live microorganisms are administered in adequate amounts in ‘probiotic’ treatments. The biggest success story in the area of probiotics has been the use of fecal microbiota transplants (FMT), wherein fecal microbes from a healthy person are used to treat recurrent diarrhea caused by an antibiotic-resistant Clostridium difficile infection in a patient. FMT treatment is under investigation as a cure for other gastric disorders.
Although the results show a lot of promise, many microbiome researchers are taking a cautious and deliberate approach before suggesting cures to diseases. After all, researchers have only just started to explore the diverse microbiome and its complex interaction with the host. For example, Helicobacter pylori – a bacterium previously shown to be a causative agent in adults for digestive diseases (such as duodenal ulcer and gastric cancer) – has also been shown to have a protective role in esophageal premalignant and malignant conditions of the esophagus and also an inverse association with asthma and allergy (4).
Given the plasticity of our own genome and early successes in manipulating our ‘second genome,’ I believe the field of medical microbiology has the potential to deliver new therapeutic strategies not only for prevention of disease but also promotion of health. And analytical science must, of course, play an essential role.
- Smith et al, “Gut microbiomes of Malawian twin pairs discordant for Kwashiorkor,” Science, 6119, 548-554 (2013).
- Riduara et al, “Gut microbiota from twins discordant for obesity modulate metabolism in mice,” Science, 6150 (2013).
- Dethlefsen and Relman, “Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation,” Proc. Natl. Acad. Sci. USA, 108, supp 1 (2011).
- Backert and Blaser. “The role of CagA in the gastric biology of Helicobacter pylori,” Cancer Res., 76 (2016).
Pratik Jagtap is a Research Assistant Professor at the Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis (USA). In 2000, he received his PhD at the Center for Cellular and Molecular Biology, Hyderabad (India). Later, during his post-doctoral research in Stefan Schuster Lab at Max-Planck Institute for Developmental Biology, Tuebingen (Germany) and Phil Andrews Lab at University of Michigan, Ann Arbor (USA), he worked on genomic and post-genomic analysis of Bdellovibrio - an endosymbiont bacterium. In 2008, he joined the Minnesota Supercomputing Institute (Minneapolis, USA) as a computational proteomics consultant and later in 2013 as a Managing Director of the Center for Mass Spectrometry and Proteomics (St. Paul, USA). His current research interest (along with Professor Tim Griffin) includes developing analytical workflows using Galaxy platform in the area of proteomics, especially in emerging area of metaproteomics, proteogenomics and data-independent acquisition (DIA) data analysis. He has authored over 20 peer-reviewed manuscripts including editing a Special issue on Microbiomes in Proteomics journal.