Revealing Time of Death: The Microbiome Edition

Forensic analysts have long sought precision when determining time of death. While on crime scene investigation television shows, the presence of insects always seems to reveal when a person died, there are many elements to account for, and the probable date may still not be accurate. Insects arrive days after death if at all (e.g., if the body is found indoors or after burial), and the stage of insect activity is influenced by temperature, weather conditions, seasonal variation, geographic location and other factors. All this makes it difficult to estimate the postmortem interval (PMI) of a body discovered an unknown time after death. One way to make estimating PMI less subjective would be to have calibrated molecular markers that are easy to sample and are not altered by environmental variabilities.

Bacterial communities called microbiomes have been frequently in the news. The influence of these microbes encompass living creatures and the environment. Not surprisingly, research has focused on the influence of microbiomes on humans. For example, changes in gut microbiome seem to affect human health. Intriguingly, microbiomes may also be a key to determining time of death. The National Institute of Justice (NIJ) has funded several projects focused on the forensic applications of microbiomes. One focus involves the necrobiome, the community of organisms found on or around decomposing remains. These microbes could be used as an indicator of PMI when investigating human remains. Recent research published in PLOS ONE examined the bacterial communities found in human ears and noses after death and how they changed over time. The researchers were interested in developing an algorithm using the data they collected to estimate of time of death. Continue reading

Unexpected connections: Gut bacteria influence immunotherapy outcomes

Over the last few years, human microbiome studies have revealed fascinating connections between our colonizing microorganisms and ourselves—including associations between gut bacterial populations and obesity, disease susceptibility, and even mood. The relationship between us and our microbial colonists—once considered completely benign, is now being revealed as an intricate, complicated partnership with the potential to redefine who “we” are in fundamental ways.

Two papers published back-to-back in the November 27 issue of Science add further to this growing body of knowledge—reporting a new and unexpected connection between gut bacterial species and the effectiveness of cancer immunotherapies in mice. The work suggests one reason why such treatments are effective in some circumstances, but not others. Both papers report that the presence of specific bacterial populations may be required for the efficacy of certain treatments, and raise the intriguing question “Could the composition of bacteria in the gut be manipulated to enhance the effectiveness of cancer treatments?” Continue reading

Manipulating Microbiota: A Synthetic Biology Exploration of the Gut

33553646_lMicrobial cells outnumber the cells of our own bodies approximately 10:1, these microbes that live on our skin and along the epithelial linings of our internal tubes make up our microbiota*, and they can have major effects on our health. Most of our microbiota are commensal organisms, living in harmony with our body, but if you suppress our immune system or greatly reduce their populations with large doses of antibiotics, and you will soon see the effects of disrupting our microbiota.

There is much interest in the microbiota that inhabit our bodies. For instance several studies have indicated that intestinal microbes can play a big part in obesity, with changes in the makeup of the microbiota being a major risk factor (1). But many of these organisms are hard to learn about—the ones that inhabit the deep folds of our gut thrive in moist, warm, anaerobic conditions with lots of specialized nutrients, conditions that are very hard to replicate in the laboratory. For that reason, we don’t know much about many of the microbes that are the most abundant within us.

The Human Microbiome Project begun in 2008 by the National Institutes of Health (2) seeks to understand human microbiota and their relationship to human health. To do this, the researchers leading the project took a metagenomic approach—using advanced DNA sequencing technologies to sequence the genomes of human microbiota and get a look at the human microbiome—without culturing the microbes.

But to truly understand their biology, and to perhaps exploit what we learn to enhance human health we need to be able to manipulate these organisms. In particular, biologists who are interested in synthetic biology would like to use these micro-organisms to monitor what is going on in our bodies, particularly our guts. What better monitor for these hard-to-access places than an organism that is already well adapted to live there?  Continue reading

Mining Genomes for Antimicrobials

searching for new antibioticsWhile looking through some “Top Ten” lists of the various science stories and discoveries of 2014, I came across a paper, published in Cell in September, describing a new approach to the search for antimicrobials. The paper’s authors screened the vast amount of genomic data from the human microbiome project against known sequences to find genes with homology to existing small molecule drug candidates.

The authors reasoned that any genes that were common across many species would be more likely to affect conserved microbe:host or microbe:microbe interactions. Having identified a large group of these gene clusters, they then homed in on a subset that was commonly found in the microbiome of healthy individuals. As a proof-of-concept, they then identified and characterized a thiopeptide molecule produced by the bacterium Lactobacillus gasseri  and showed that it had the expected antimicrobial activity. The Cell paper was the first report of the characterization of any small molecule drug candidate isolated from the human microbiome. Continue reading

Christensenellaceae—A Natural Way to Stay Thin?

microbiome studies show how bacterial colonists influence healthA study published in the Nov 6 issue of Cell outlined results suggesting that an obscure family of bacteria colonizing the human gut may be inherited and may also have a direct influence on body weight. The paper is the first to identify such an association and to link a particular microbial colonist with lower BMI. Continue reading

About the Wild Life in Our Homes (at least the single-celled kind)

The initial paper from the Wild Life in Our Homes study by Dunn et al. found a correlation between the presence of dogs and specific bacterial communities on pillowcases and TV screens.

The initial paper from the Wild Life in Our Homes study by Dunn et al. found a correlation between the presence of dogs and specific bacterial communities on pillowcases and TV screens.

Back in the fall, I received a sampling kit, an Informed Consent form and instructions for collecting samples for the Wild Life In Our Homes citizen science project. I carefully swabbed the requested surfaces: exterior and interior door trim, kitchen counter tops, pillowcases, etc., and sent my samples in. I later received confirmation that my samples had been received and again later confirmation that they were being analyzed.

The first paper from this project has been published by Dunn et al. in PLOS ONE (Home Life: Factors Structuring the Bacterial Diversity Found within and between Homes). This initial report covers the first 40 homes sampled, all from the Raleigh-Durham, NC, USA area. Volunteers sampled their homes in the Fall of 2011, collecting specimens from nine areas: cutting boards, kitchen counters, refrigerator, toilet seat, pillowcase, door handle, TV screen, and interior and exterior door trim. The scientists used direct PCR and high-throughput sequencing to sequence the bacterial 16S rRNA gene from the submitted samples. By doing this they were able to estimate the diversity within each sample—they did not distinguish between live and dead organisms, and they did not sequence anything other than the bacterial 16SrRNA, so this study is limited to bacteria. Continue reading

My Microbiome Made Me Do It

When I was in school I learned that there were two different kinds of bacteria, the nasty ones (pathogens) that could make you sick and the nice ones (commensals), which simply colonized you and did nothing much except occupy a spot that could otherwise be taken up by a pathogen. Any role for those commensal bacteria in health and disease was assumed to be no more than that of a harmless squatter. In recent years, studies of this benign microbial population (microbiome studies) have begun to reveal many more intriguing details about how they affect our health and wellbeing. Maybe it’s not so surprising that “good” bacteria could be good for our health—but could they actually affect how we behave? This month, a review in Science summarized new findings that indicate that this is indeed the case—at least for certain animal populations. Could it be true for humans as well? Could our colonizing organisms actually influence how we feel and what we do? Continue reading

Dark Matter, Rosetta Stones and Hordes of Beasties

Key regulatory roles are being identified for non-coding DNA sequences, once considered "junk".

The more you know, the more you find out about how much you still don’t know. So goes the old saying. A recent New York Times article nicely illustrated the practical outworking of this phenomenon in the context of cancer research. The article highlighted several recent papers and reviews showing how much progress has been made over the last ten years, and illustrating how the focus has changed to incorporate not only research on protein-coding sequences, but also the “dark matter” of noncoding RNAs and the potential contributions of genes from the millions of bacteria that colonize the human body.

In 2000, a review describing six key traits of cancer cells was published in the journal Cell, it is one of the most cited papers from that journal. In March of this year, the same authors published an update entitled Hallmarks of Cancer: The Next Generation describing current knowledge of the mechanisms underlying the same six traits, and adding two new ones. Continue reading