Translating the Microbiome

Last week, the Wellcome conference “Exploring Human Host-Microbiome Interactions in Health and Disease” took place. This was an excellent opportunity for microbiome researchers, from either a basic research or medical background, to exchange ideas on the next steps for taking science from the bench to bedside. Editorial Community Manager Sam Rose @rosenovich reports on some of the highlights from #HMIHD17.

Last week I was pleased to have to chance to visit the Wellcome Genome Campus in Hinxton (UK). A number of meetings attracting top-notch researchers from across the globe happen at this stunning institute. These conferences focus on the hottest areas in genomics, and so the program would not be complete without our friend (/foe), the microbiome (i.e., the microorganisms that inhabit the human body).

All the session themes had a strong focus on translation. Coming from a biology background myself, it was impressive to see such progress in moving microbiome research into the clinic; the potential applications certainly went beyond probiotics (though this is a hot area of research), to topics such as personalized medicine, fecal transplantation, and other more surprising topics.

The introductory talk was by Patricia Hibberd (Boston University, USA). Facts we know about the microbiome were first listed, such as that the human microbiome composition stabilises by age 3, and that it varies by age and geography. Dr Hibberd then discussed what we don’t know, such as much of how the microbiome functions beyond the gut, the non-bacterial microbiome (i.e., viruses, fungi, archaea, and protists in the human body), and local vs. distant effects.

In addition, there are still many big questions that need answering:

  • What are the unclassifiable sequences getting picked up?
  • What is the cause and effect of the microbiome in disease?
  • How can we change the microbiome in a safe and predictable way?
  • Does diet affect everything?

Dr Hibberd went on to describe the probiotics and prebiotics market, which is forecasted to be worth $45 billion globally in 2018. While there is increased investment in this area, it is incredibly hard to get products to market due to FDA restrictions and procedures. This frustration seemed to be echoed throughout the room, though many were surprised at just how restrictive it was in the USA compared to other countries.

The first session, chaired by Karen Scott (University of Aberdeen, Scotland), was on one of my favourite topics – fecal microbiome transplatation! Known at FMT, or stool transpantation, this process involves the transplantation of fecal bacteria from a healthy individual into a recipient.

Gillian Gardner (Waterford Institute of Technology, Ireland) talked about her research on pigs, which are generally a good model for humans. FMT was administered orally, and, interestingly, effects from the procedure were observed in offspring of mothers who had been given FMT. This indicates that changes to the microbiome can cause effects at least one generation down.

In terms of actual effects, FMT caused a decrease in beneficial microbes, and an increase in potentially pathogenic microbes. Furthermore, early-life intestinal microbiota impacted the lifetime phenotype, including decreased pig growth. While the mechanism here is unknown, this is clearly an example of FMT having unfavorable effects.

In the next session “Beyond the micobiome: local and distant effects”, Gary Borisy (The Forsyth Institute, USA) discussed his fascinating work on understanding biofilm structure. He demonstrated how microbiome biogeography can be revealed through spectral imaging and genomics, showing beautiful images of “who sits where” in terms of microbial species. Often very different species live alongside each other, which makes sense, since similar species would be likely to outcompete each other.

The challenge now is to interpret the functional significance of the microbiome structures, then understand how they work, and how they are formed and maintained.

Karen Scott (University of Aberdeen, UK) gave a comprehensive background on what we know about probiotics and prebiotics, and proposed redefining these to not just refer to gut microbiota as they often do.

Prebiotics provide substrates for bacteria that are already present in the body. There are known prebiotics in foods such as onions and leeks. They are also added as ingredients, such as xylitol in chewing gum, which provides a substrate for beneficial bacteria to outcompete “bad” bacteria.

Charu Kaushic (McMaster University, Canada) discussed her research on microbiota in the female genital tract. Her team looked at the contraceptive DMPA in Kenyan women, which is an extremely popular drug among African, to the point where it was difficult to find women not on DMPA for the control group.

Dr Kaushic showed that DMPA is associated with increased bacterial species diversity. Diverse flora is in turn associated with negative reproductive outcomes and higher susceptibility to sexually transmitted infections, including HIV. This important research warrants further investigation.

Joanne Pennock (University of Manchester, UK) gave a nice talk on the involvement of Staphylococcus aureus in eczema. Her study showed that the bacteria were found deep in the skin barrier, and induced cytokine release that caused symptoms of atopic dermatitis.

The gut-brain axis is an intriguing subject that several groups are currently researching. Carolina de Weerth (Radbound University, Netherlands) showed that gut disbiosis (i.e., microbial imbalance) is associated with psychopathology. Environment and early-life stress are associated with colonization, and there may be sensitive periods for effects of microbiota on development. However, most data are from animal models and not currently proven in humans, warranting further studies before we can draw solid conclusions.

The negative impact of antibiotics on society are increasingly being realised in terms of antibiotic resistance. Jon Widding Fjalstad (University of North Norway Hospital, Norway) presented a systematic review on the impact of antibiotics on neotnatal gut microbiota. In addition to promoting resistance, he showed that antibiotic exposure potentially induces disease-promoting microbiota. More high-quality data are needed to confirm this hypothesis.

It was fascinating to learn more about how our resident microbes may potentially be involved in human health and disease in ways that we previously never considered; though as Patricia Hibberd noted, cause and effect still needs to be established in many cases. In addition, issues such as reproducibility are highly important to consider before making assertions based on metagenomic data. There is still a lot we don’t understand and many results are still quite preliminary.

Nevertheless, great steps have been taken in this field to date, and the microbiome is certainly catching the attention of medical professionals.

The text and illustration in this blog post are by Hindawi and are distributed under the Creative Commons Attribution License (CC-BY). All photos: Sam Rose (also CC-BY).