From @CNNAshley at @CNN: Why NASA is sending a superbug to the space station 

Just a quick post here.  There is a new CNN story that may be of interest.

An antibiotic-resistant superbug will launch from the same pad where the first manned mission to the moon lifted off to be studied on the International Space Station.

Source: Why NASA is sending a superbug to the space station –

I confess I am skeptical of some of the scientific claims being reportedly made by Dr. Anita Goel. For example  – see this:

I have this hypothesis that microgravity will accelerate the mutation patterns. If we can use microgravity as an accelerator to fast-forward and get a sneak preview of what these mutations will look like, then we can essentially build smarter drugs on Earth

We know lots of ways to accelerate mutation rates on earth – radiation, making mutations in DNA repair genes, other mutagens, and so on.  Why would using microgravity be worthwhile compared to those other methods?  I do not know.

Also – each agent that leads to an increase in mutation rate has it’s own spectrum of types of mutations that it accelerates.  Who is to say that microgravity will increase mutations in the same way that they would occur on earth with just an increase in speed?

And then there is this:

“If indeed we can use the ISS as an accelerator, an incubator, to know what future mutations of superbugs like MRSA will be, we use that info to develop better algorithms on Earth to inform drug discovery and faster ways to get to smarter drugs that are more personalized and more precisely targeted to a bug or strain at hand. We can have those drugs ready before the mutations even show up on Earth.”

Same issues I guess.  Even if microgravity led to an acceleration in the mutation rate, I just don’t see how that will help anticipate the mutations that will show up on Earth.

I am all for doing research on microbes in space, for many reasons (e.g., see  And certainly microgravity could be an interesting tool for studying some processes in microbes.  But I am skeptical of some of the claimed goals of this project.  Not that I object to this work – I think we can learn a lot from such experiments – just not what is being claimed here.  And to be honest – anything that gets the public to think more about microbes can potentially be a good thing, it just should be presented carefully.

I assume there is much more to the science here than is being reported in the news stories.  The basic science part of this sounds interesting.  I am just deeply skeptical of the claimed applied value (e.g., predicting future mutations of MRSA).

Investigating the antibiotic resistome of rural and peri-urban Latin America

For many years, efforts to profile the antibiotic resistome of the human gut focused exclusively on two extremes of human society: Western, industrialized cities and remote hunter-gatherers. While these studies were undoubtedly important, they overlooked the majority of the world’s population, which exists somewhere between the two extremes. Indeed, three-quarters of the world’s population lives in low- and middle-income countries [1-2], with almost a billion in slums (World Health Organization) [3]. In rural areas, though many have intermittent access to towns and cities, 16% of the population does not use improved drinking water sources, and 50% still lack access to improved sanitation facilities (United Nations Millennium Development Goals Report 2015) [4]. From an antibiotic resistance perspective, contact with both subsistence agriculture (including livestock and soil) and population centers (including processed foods and a dense, diverse population) could increase the diversity of bacteria and antibiotic resistance to which these populations are exposed. Furthermore, the high incidence of infectious disease and widespread availability of antibiotics without prescription, coupled with a lack of clean water, could contribute to the spread of bacteria and antibiotic resistance genes. In fact, industrializing countries were responsible for the majority of the worldwide 36% increase in antibiotic use between 2000 and 2010 [5]. To address this critical gap in our understanding of the human resistome, we recently published a large-scale study of the microbial communities and antibiotic resistance genes associated with the human gut, waste disposal systems, and the environment in a rural Salvadoran village and a Peruvian slum (“Interconnected microbiomes and resistomes in low-income human habitats”) [6]. I led this study along with Pablo Tsukayama as part of our respective PhD thesis projects in Gautam Dantas’s lab ( at Washington University in St Louis.

A prefabricated home in the rural village, El Salvador
(Photos courtesy of Giordano Sosa-Soto and Melissa Mejía-Bautista)

We began our study in 2011 with the help of Dr. Douglas Berg (Professor Emeritus, Washington University in St. Louis), who set up a collaboration with professors Maria Teresita Bertoli, William Hoyos-Arango, and Karla Navarrete at the Universidad Dr. José Matías Delgado (UJMD) in San Salvador to investigate the microbiota of rural Salvadorans. In parallel, we began a collaboration with the Universidad Peruana Cayetano Heredia (UPCH) in Lima, Peru, to study the microbiota of residents of urban slums. In retrospect, I had signed up for a uniquely challenging graduate experience. A mudslide destroyed the first village we had intended to study, and the village we finally selected was inaccessible during the rainy season when the mountainous dirt roads became impassable. There was exactly one manufacturer of dry ice in San Salvador, who was able to produce just enough dry ice in a single day for us to complete sample collection. Furthermore, though it may be difficult to believe, human feces was the easiest of the samples to import into the US: soil and animal feces, with their potential for the introduction of invasive species, are strictly regulated and required not only import permits but federal inspections of our laboratory space. To top it off, my Spanish was limited to one college semester and a year of frantic Rosetta Stone, and Gautam speaks no Spanish at all, which severely restricted our ability to communicate on the ground. Now in my postdoc, I am sometimes amazed that Gautam was willing, in his first five years as a PI, to invest serious resources in two such high-risk projects.

The insulated box that shipped samples between El Salvador and the US

Despite the challenges, we were able to successfully collect hundreds of samples from the village at multiple time points over two years, forming the basis for a longitudinal and cross-sectional profile of the microbiota of rural El Salvador. The lion’s share of the credit for this achievement goes to the Salvadoran team, whose creativity and dedication in solving the numerous obstacles that stood in the way of the project was outstanding. The primary responsibility of the faculty at UJMD is the teaching and practice of medicine. Unlike in the US, where we expect to be compensated for our research efforts, our collaborators advanced our research in their free time out of a passion for science and a desire to see the nascent Salvadoran research infrastructure grow. They used their experience treating people in rural locations to help decide which samples to collect, doggedly pursued regulatory officials to get the study protocol approved, and coordinated the sample collection with residents of the village. When a tree downed in a hurricane knocked out power for two weeks to the sole university laboratory where our samples were stored, they miraculously found alternate refrigeration sources. Two of the authors on the paper, medical students Melissa Mejía-Bautista and Giordano Sosa-Soto, even interrupted their medical education for a year to learn molecular biology in our lab, greatly contributing to the progress of the data production and introducing molecular biology techniques to their university.

Sterile containers lined up in preparation for fecal sample collection

In addition to our counterparts in El Salvador, I was shocked by the level of involvement and assistance we received from the village itself. Although most residents are subsistence farmers who are sometimes employed nearby, the village is extremely well-organized and headed by a mayor with a clear vision for their future. With the help of a local charitable organization, Epilogos Charities, Inc., the village had pursued a number of community improvement initiatives, including honey and fish farming co-operatives. The community also had prefabricated houses and composting latrines for each household, which use heat, dessication, and high pH to sterilize feces over the course of several months; the sterilized waste is then used as fertilizer for agricultural plots. The mayor was very proactive about checking in with us during each sample collection about any new information or benefits that had resulted from their participation in the study, and we sincerely hope that the information we gathered about the composition of their gut microbiota, as well as potential sources of antibiotic resistance genes, will lay the groundwork for future investigations and public health interventions.

Double-vault composting latrines

For example, studies such as ours may spur improvements in sanitation infrastructure in rural El Salvador, peri-urban Peru, and beyond. Given the enormous diversity of antibiotic resistance genes in the environment, the ready availability of antibiotics, and the rapid globalization and urbanization of our world, one of the best strategies for curbing the development of antibiotic resistance will be reducing the incidence of infectious disease before antibiotics become necessary. To do so, we will need creative sanitation solutions that can be deployed in places with limited income and limited water. Recently, a team of engineers at Washington University has begun work on improving the sterilization of human feces using composting latrines. Additionally, soon after our project began, El Salvador banned Intestinomicina, a cocktail of antibiotics available over-the-counter to treat gastrointestinal ailments. Although it was banned for unrelated health concerns, our research may draw attention to the ease of transfer of antibiotic resistance genes, leading to better stewardship of antibiotics.

A household agricultural plot


  1. The World Bank Group. Data: Countries: Middle Income. ( (2015)
  2. The World Bank Group. Data: Countries: Low Income. ( (2015)
  3. World Health Organization. Global Health Observatory (GHO) Data: Urban Health. ( (2015)
  4. United Nations. The Millennium Development Goals Report 2015. ( (2015)
  5. Van Boeckel, TP et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect. Dis. 14, 742–750. (2014)
  6. Pehrsson EC, Tsukayama P, Patel S, Mejía-Bautista M, Sosa-Soto G, Navarrete KM, Calderon M, Cabrera L, Hoyos-Arango W, Bertoli MT, Berg DE, Gilman RH, Dantas G. Interconnected microbiomes and resistomes in low-income human habitats. Nature 533: 212-216. (2016) (

Ants as (Possible) Vectors of Bacteria in Hospital Environments

Not really sure what to think about this article:  Ants as Vectors of Bacteria in Hospital Environments. Published in the Journal of Microbiology Research and authored by Bruna Rafaela Machado Oliveira, Luciano Ferreira de Sousa, Raquel Chalá Soares, Thiago César Nascimento, Marcelo Silva Madureira, Jorge Luiz Fortuna.

In a quick scan the science seems reasonable.  They collected ants, cultured microbes from them, screened the microbes for various resistances, and then analyzed the data.  And some of bacteria were identified as closely related to known pathogens

So that is certainly something to be aware of.  I am just not sure what the implications of this finding are.  Fortunately, the authors are at least somewhat cautious in their conclusions

The results show that the ants captured are possibly working as carriers of pathogenic bacteria. Transmission may take place directly, when ants crawl up a patient’s skin, or indirectly, when they run on medical devices. Besides the fact that these ants carry a significant number of clinically important bacteria in hospital settings, another relevant finding was the resistance to selected antimicrobials, which increases the risk of HAIs, especially in ICU inpatients who, in most cases, are immunodepleted.

The great importance of bacteria carried by ants in hospital environments lies in the resistance to antimicrobials they develop, highlighting the need for increased awareness in healthcare organizations as to the adoption of strict prevention measures. Such initiatives may be as simple as washing hands properly and as complex as devising sensible courses of antimicrobials to inpatients or conceiving efficient pest control programmes.

Despite the confirmation that ants carry microorganisms, our results have not afforded to clarify the precise role these insects have in HAIs. Further studies should be conducted to assess the risk of infection in hospital settings potentially colonized by ants.

So – don’t go out to kill at the ants everywhere based on this article.  But certainly it is worth keeping in mind that organisms other than humans may be involved in spreading microbes around in a hospital environment.


Worth a look: Special issue of @NYASAnnals on “Antimicrobial Therapeutics Reviews” 

Figure 2 from Guthrie and Gardy 2016.


There is a whole issue of the Annals of the NY Academy of Sciences that may be of interest.  The focus of the issue is on Antimicrobial Therapeutics Reviews.

Some of the papers are freely available.  These are

Definitely worth taking a look.

Worth a read: Post by @SharonJPeacock & Claire Chewapreecha on tracking pathogen/biothreat behind #melioidosis

Quick post here.  Nice short post in the On Health Blog at Biomed Central on studies of the population genomics of Burkholderia.

Melioidosis is a frequently fatal infectious disease caused by a bacterium (Burkholderia pseudomallei) found in soil in certain parts of the world. We have known about melioidosis for many years, but it’s only in the last 25 years that we have started to understand it better. So, what’s changed?

Source: Tracking the movement of a deadly pathogen and biothreat agent – On Health

Important story by @HelenBranswell in @statnews: Why the advice to take all your antibiotics may be wrong

Quick post. This is a very important read by Helen Branswell in STAT for those interested in antibiotic resistance.

Patients are told to finish their antibiotics, even if they feel better, but that guidance may be exacerbating antibiotic resistance, some experts say.

Source: Why the advice to take all your antibiotics may be wrong



From genomes to phenotypes: Traitar, the microbial trait analyzer

There is an increasing number of studies with a large number genomes recovered from isolate, metagenome, or single cell sequencing. To bridge the gap between the available genome sequences and available phenotype information, we have developed Traitar, a bioinformatics software to phenotype bacteria based on their genome sequence (see workflow below) . Traitar includes phenotype models for predicting 67 traits such as the use of different substrates as carbon and energy sources, oxygen requirement, morphology, and antibiotic susceptibility, and it provides the means to inspect the protein families (Pfams) that gave rise to these phenotype predictions.


In a paper recently published in mSystems (, we describe the application of Traitar to two novel Clostridiales species with partical genomes recovered from metagenome shotgun sequencing of commercial biogas reactors. Traitar could verify an expert  metabolic reconstruction and furthermore pinpoint additional traits that were missing in the manual metabolic reconstruction.

The software is easy to install and run. It only requires a nucleotide or protein FASTA file per sample as input. Users can inspect the phenotyping results of  from Traitar  for their genome sequences of two prediction modes (phypat and phypat+PGL) through heatmaps (see example of Traitar applied to single-assembled genomes below; Fig 5 in Traitar paper) and flat text files. For phenotyping a single genome, Traitar only requires a couple of minutes. Computation is multithreaded (parallelized) and scales to data sets with hundreds of genomes. We also offer a web service for data sets of up to around ten genomes. If you have larger data sets and troubles running the Traitar stand-alone tool get in touch with us (contact details below).

To build and validate the phenotype models in Traitar, we have used phenotype data from the Global Infectious Disease and Epidemiology Online Network (GIDEON) and Bergey’s Systematic Bacteriology. Internally, the models were created using a machine learning method, namely L1 regularized L2 loss support vector machine trained on information about the presence and absence of protein families as well as ancestral protein family gains and losses.

Some word of advice when applying Traitar for phenotyping your genomes:
The training data from GIDEON and Bergey’s does not cover all known bacterial taxa and some with more data than others. Thus, some of the phenotypes might be realized with different protein families in taxa that are less well represented here and classification accuracy for these taxa be less than for others. Since Traitar provides the Pfam families responsible for your phenotype prediction, you could cross reference the phenotypes predicted by Traitar and the associated protein families with a targeted metabolic reconstruction approach.

We are currently working on incorporating new phenotypes and on further extending the existing phenotype models. For instance, we will apply Traitar to several hundred isolate genomes of the pathogen Pseudomonas aeruginosa to learn phenotype models of antibiotic resistance. We will keep updating the software and models, so please regularly check out our GitHub or Twitter. Traitar is designed to easily incorporate new prediction models. If you have data for phenotypes of interest please get in touch with us. We’re  also preparing a stand-alone software to allow users to train their own phenotype models.

Aaron Weimann: @aaron_weimann
Andreas Bremges: @abremges
Alice C. McHardy: @alicecarolyn

Web service:
Web service and general BIFO software support:

Legionella bacteria in Parliament showers 

So in searching for news stories about bacteria in buildings I found another one with some political connections:

Source: Legionella bacteria spread into Parliament showers –

This follows on my post from earlier: “Derelict White House” contaminated by leptospirosis causing bacteria #WhiteHouse

As with that post, my headline here is not the whole story.  Yes Legionella was found in the showers in Parliament.  But this was in the Parliament in Malta not (as I assume people would assume) the UK.  Still this may have some impact on the EU since Malta will be hosting many EU meetings as part of it’s “six month EU presidency. “

Of possible interest: Biosafety Design Initiative courses and more

Got pointed to this Biosafety Design Initiative on Twitter

It may be of interest to some. They have courses and other activities connected to microbes in the built environment.  From their site:

The Biosafety Design Initiative brings together experts at University College London from the UCL Centre for Clinical Microbiology for biomedical research and UCL Faculty of the Built Environment for architecture, construction and project management.

With our partners in microbial engineering and infection control we work together in designing the most successful interventions and supporting systems for the control and reduction in transmission of infectious diseases – wherever they occur in the world.

The aim is to support an interdisciplinary community of practice from the fields of clinical microbiology, design, engineering and project management. We provide online and interactive series of short courses that cover principles of biosafety design, measurement of infectious diseases, evaluation of clean and controlled environments and the design of transformative diagnostics processes, space and infrastructure.



The concept of hygiene and the human microbiome.

(This post was written by Roo Vandegrift at the University of Oregon)

I was recently asked to spearhead the writing of a review centered around the interaction between the concept of hygiene and our increasingly nuanced understanding of the human skin microbiome for the Biology and the Built Environment (BioBE) Center at the University of Oregon.

This review began with an invitation from Dyson to conduct an impartial review of hand drying studies, which have been mired in competing interests and faulty methods. We saw an opportunity to not only provide an unbiased review of the literature, but also to ask a more fundamental question: how should hygiene be defined in light of our evolving perspective of the human and indoor microbiome?  We delivered a brief summary to Dyson (here) and then built upon that work to develop this question.  

As we started digging into the body of literature on hand hygiene, two things struck us as peculiar: the first was that in the hundreds of studies explicitly examining hygiene, the concept was never explicitly defined; the second was that there seemed to be a clear division between skin microbiological investigations coming from clinically and ecologically informed perspectives, with clinical research generally relying on older cultivation-dependent techniques. These two issues became the drivers for our review, and our goal was to provide an explicit definition of hygiene that would help to bridge the gap between the clinical skin microbiology literature and the newer human-associated microbial ecology literature. We were then able to use the body of literature on hand drying as a case-study to examine the implications of using a microbial ecology-based approach to defining hygiene.

You can read the full review as a preprint on bioRxiv now:

You can read the shorter, white page summary of the review on the BioBE blog:

Our review is broadly split into three sections: one section summarizing previous work on hygiene, one section briefly outlining previous work on human-associated microbial communities (including those found on the skin and in the built environment), and one section attempting to synthesize the two.

In the first section, we start seeing some of the limitations of cultivation-dependent methods, and how those limitations combine with implicit assumptions about the concept of hygiene. One thing that stands out to me from a thorough reading of clinical literature on hand hygiene is how often the idea of sterilization is used as a stand-in for the idea of hygiene — one result of the complete adoption of the germ theory of disease is the common misconception that “all microbes are germs”. This is apparent in the majority of studies of hygiene, particularly reflected in the focus on bulk reduction in microbial load, regardless of the identities of those microbes. I would, however, like to acknowledge Allison Aiello and Elaine Larson’s careful 2002 review, “What is the evidence for a causal link between hygiene and infections?“, which goes considerably beyond thinking of all microbes as germs and examines hundreds of studies, pulling out those that actually examine health outcomes as a dependent variable. Their review lays the conceptual foundations for what we are trying to do in our review.

In bridging into the second section, which outlines human-associated microbial ecology, we wanted to clearly illustrate the advances in techniques that the field utilizes. We put together this simple, but hopefully informative, conceptual figure to help:

Figure 1: Cultivation-dependent methods (A) are commonly used to study aspects of hand hygiene; many microbes are not detectable using this methodology (represented in grey). Handwashing reduces bulk microbial load, and cultivation yields data showing changes in the numbers of colony-forming units (counts); some studies identify colonies using morphological or molecular methods, yielding limited taxonomic information. Cultivation-independent methods (B), including high-throughput DNA sequencing, are commonly used to study the microbial ecology of the skin. Using these methods, it is possible to quantify alterations in relative abundance of bacterial populations with treatment (such as handwashing), obtain deep, comprehensive taxonomic diversity estimates; depending on technique, it may be possible to also obtain information on functional metabolic pathways (using metagenomics), assessment of proportion of the community that is active (using rRNA / rDNA comparisons, or live/dead cell assays), among other things.

It is clear that hygienic practices may interact significantly with human-associated microbial ecology. We highlight and summarize some of the important ecological factors that may interact with hygienic practice in a second conceptual figure:

Figure 2: Conceptual illustration of important ecological factors impacted by hygienic practice. Dispersal (a) is the movement of organisms across space; a patch of habitat is continuously sampling the pool of available colonists, which vary across a variety of traits (dispersal efficiency, rate of establishment, ex host survivability, etc.) (Vellend 2010); high dispersal rates due to human behaviors (e.g., microbial resuspension due to drying hands with an air dryer) have the potential to disperse both beneficial and harmful bacteria alike. Protective mutualisms (b) function through the occupation of niche space; harmful microorganisms are excluded from colonization via saturation of available habitat by benign, non-harmful microbes (Poisot et al. 2014). Host/microbe feedbacks (c) occur via the microbiota’s ability to activate host immune response, and the host immune system’s ability to modulate the skin microbiota (Chehoud et al, 2013; Garcia-Garcera et al, 2012; Oh et al, 2013) — multiple pathways, including IL-1 signalling (Naik et al 2012) and differential T-cell activation (Seneschal et al 2012), are involved — such feedbacks between host immune response and the skin microbiota are thought to be important to the maintenance of a healthy microbiota and the exclusion of invasive pathogenic microbes (Zhang et al 2015). Environmental filtering (d) works on the traits of dispersed colonists — microbes that can survive in a given set of environmental conditions are filtered from the pool of potential colonists (Vellend 2010): the resources and conditions found there permit the survival/growth of some organisms but not others. The importance of diversity of the microbiota to each of these ecological factors should not be underestimated; interactions between taxa may modulate their ecological roles, and community variation across a range of ecological traits may be altered by changes in community membership or structure (HMPC, 2012).

Coming to the third and final section, it should be clear to the reader that future work on hygiene would benefit from integrating modern techniques and an ecological perspective from recent human microbiome research. To facilitate that, we believe that it would be helpful to have a clear, concise definition of hygiene from which to work. This is probably the most important moment from our paper:

The evidence that microbes are essential for maintaining a healthy skin microbiota supports the idea that hygienic practices aimed at the simple removal of microbes may not be the best approach. Rather, hygienic practices should aim to reduce pathogenic microorganisms and simultaneously increase and maintain the presence of beneficial microorganisms essential for host protection. It is clear that microbial colonization of the skin is not deleterious, per se. Humans are covered in an imperceptible skim of microbial life at all times, with which we interact constantly. We posit that the conception of hygiene as a unilateral reduction or removal of microbial load has outlived its usefulness and that a definition of hygiene that is quantitative, uses modern molecular biology tools, and is focused on disease reduction is needed. As such, we explicitly define hygiene as ‘those actions and practices that reduce the spread or transmission of pathogenic microorganisms, and thus reduce the incidence of disease’.

Let me repeat that last part: we explicitly define hygiene as ‘those actions and practices that reduce the spread or transmission of pathogenic microorganisms, and thus reduce the incidence of disease’. We feel that it is incredibly important to define hygiene in terms of health outcomes, not just in terms of reduction in number of microbes. This allows for research (consider, for example, probiotics research) to address the root of hygienic practice: cleanliness in pursuit of improved health.

From the hand drying example, it is clear that a standard definition of hygiene would be helpful: it turns out the vast majority of research on the hygienic aspects of hand drying has been funded by either the paper towel industry or the blow drier industry as advertising tools. There appears to be something of a feud going on between these two competing industries. Sadly, there is much about the current state of hand drying literature that is clearly partisan, and it is difficult to evaluate claims from either side because they define hygiene differently.

The hand drying literature can be separated into two opposing divisions: one attempting to demonstrate that the newer air dryers are as hygienically efficacious as paper towels, and the other attempting to discredit the newer technology in favor of paper towels. While both divisions utilize bulk reduction in microbial load as a proxy for hand hygiene, research from the first division largely focuses on the potential of wet hands to transfer microbes and the ability of air dryers (whether warm or jet) to effectively dry hands: the hypothesis in this case is drying is hygienically efficacious if hands are dry and new microbes are not acquired through the process. Research from the second division tends to focus on the risk of air dryers to spread microbes throughout the environment by aerosolizing moisture from the hands: the hypothesis in this case is drying is hygienically efficacious if new microbes are not acquired through the process and if production of aerosols are minimized. It is difficult to compare the two divisions because many of these studies include methodological issues (e.g., variation in protocols, lack of appropriate controls or statistical analyses) that make it difficult to compare results across studies.

Despite there being an obvious interplay between these two divisions, many of the concerns on either side remain unaddressed. Utilizing a definition of hygiene that explicitly relies on reduction in disease spread would address concerns on both sides of the debate: there is currently no evidence linking aerosolization of residual moisture (and associated microbes) with the actual spread of disease. Likewise, despite demonstrations that wet hands allow for increased bacterial transmission, there does not seem to be evidence linking wet hands after washing to deleterious health outcomes. The complex ecological context of the hand microbiota may modulate effects of both aerosolization and prolonged moistening. Additionally, the majority of hand drying research largely ignores the relative hygienic contribution of the hand washing step; understanding the relative contribution of washing to hygienic efficacy is necessary to put the hand drying literature in proper context.

The experience of working on this review has been incredibly positive: I’ve gotten to read deeply in corners of the scientific literature that I would not have expected I would be delving into even six months ago, I’ve learned a number of beautiful and startling things, and I believe that we have been able to contribute something necessary and worthwhile to the scientific discussion of hygiene. There is a gradual paradigm shift occurring right now in the clinical sciences, with germ theory being gently replaced by a more nuanced theory of disease that takes into account the beneficial role that our symbiotic microbiome plays; this review, I hope, will be a helpful building block for that new paradigm.