Carl Yeoman

Assistant Professor of Microbiology
Department of Animal and Range Sciences
Montana State University

Arthritis and the Microbiome

Picking up some good press on a recent paper of ours describing the microbiome changes associated with rumatoid arthritis. A very interesting story where you see a loss of sex and age delineations of the gut microbiome in arthritis-susceptible mice. Their disease susceptibility is driven by human transplanted HLA genes. These HLA genes elicit the same phenotype in humans. Check it out the discussion in the Mayo clinic news, Healthcare Purchasing News (Article: Sick to Your Stomach), at Science daily, on MESORX, The UK Daily Mail, Business Standard and in various blogs.

Praise for Illumina

I recently purchased an Illumina MiSeq for the lab at MSU. So I was very happy to see the Illumina plug by one of my favorite researchers, Jonathan Eisen:

http://phylogenomics.blogspot.com/2012/07/is-illumina-duct-tape-of-sequencing.html

Whirlwind Start at MSU

Well I've been very quiet for the past couple of months as I kickstarted my track to tenure at MSU. In the past ~9 weeks, I have been in 4 countries, and several cities in montana. I was an invited speaker at the 5th annual Bertinoro Computational Biology meeting in Bertinoro, Italy (amazing place! with equally amazing people). I have been teaching Advanced Ruminant Nutrition to 8 very talented graduate students. I have written several grants (fingers crossed). Perhaps the majority of my time has been spent kicking off several research programs.

Goodbye, Columbus

A great analogy to the state of scientific funding this month in Genome Biology

Nature again triumphs over human intervention

It isn't so surprising is it? After-all nature has had 3.5 billion years of evolutionary tinkering since life emerged to optimize every little detail. Yet we in our infinite arrogance continue to believe we can do it better. Occasionally we can to some extent when we want to shift that optimum (i.e. domestication) but otherwise we have almost invariably failed. A classic example is formula vs. breast milk, which for the sake of brevity I won't go into here suffice to say I was stunned during a well child visit with my son earlier this year to hear our family doctor suggest formula as an option.

A report published this week in the archives of disease in childhood has found that children born by Cesarian section were at least twice as likely to become obese than those born by natural vaginal delivery. Now I'm not saying Cesarian section has no place as a medical option, in fact in a number of cases it is important to the safety and well being of mother and child, but the concept of elective Cesarian is both naive and selfish.  Lets talk microbiology, Maria Dominguez-Bello has already shown that neonates born naturally acquire the microbiota of their mothers vaginal canal, while those born via Cesarian acquire the microbiota of their mothers skin. The vaginal tract of healthy reproductive aged females are almost exclusively colonized by lactobacilli. In a recent analysis we performed, this ranged from ~60% - 99%. Lactobacilli have a long history of being associated with human health, being perhaps the best known probiotic and linked to the suppression of Atopic dermatitis, the prevention of Carcinogenesis, IBD and Cardiovascular disease, maturation of immune function and even brain development (many of these, however, remain to be proven beyond a reasonable doubt).  In contrast, common skin bacteria include Staphyloccus, Streptococcus, Neisseria and Esherichia, who have collectively been implicated in Septicemia, Infective endocarditis, Pneumonia, Toxic shock syndrome, Rheumatic fever, Otitis media, Conjuctivitis, Meningitis and Necrotizing fasciitis to name a few. I'm proud to say my wife not only gave birth to all three of our children naturally but she did so without any pain relief. She has also breast fed all of our children; all of this despite the pain, the restrictions and the bodily alterations. She is still the most beautiful women I have ever met and the best mother in the whole world and I am proud of her selflessness.

$45 million to the Global Agricultural Research Alliance

I have recently joined the Global Agricultural Research Alliance, an international collaboration of great scientists working towards common goals in Agriculture. The project is being led from New Zealand, with Dr Bill Kelly (Agresearch) heading an audacious effort to sequence the genomes of 1000 rumen bacteria and Dr's Peter Janssen and Gemma Henderson leading an effort to characterize the microbial diversity of ruminants. The NZL government has chipped in $45 million and Eddy Rubin (JGI) is providing sequencing power

Blog 0 I am going to Blog

I have been meaning to start blogging on my site for some time now and are finally making a commitment. My current thinking is weekly with room for more where necessary. I realize I have no followers, but I figure if I build it they may come? If not it'll help get my thoughts in order anyway. I follow a few blogs such as Jonathan Eisen's The Tree of Life and Elio Schaechter's Small things considered and in all cases I didn't start following them until well after they were operating. Both of those blogs are great by the way and if you don't follow them already you should. 

Blog 1 Are Designer Microbiomes in Our Future?

?2/25/12

I came across this article (click for link) the other day about a synthetic organism based on E. coli that researchers hope will produce different colors in response to various stimuli. The organism, called E. chromi, potentiates a number of diagnostic roles, but one in particular has caught the attention of biology bloggers. The idea that following an inoculation, E. chromi could evaluate your gut environment and report back by affecting the color of your feces. The idea, however comical it may appear, appealed to me but seems only the first step in a long line of biotechnological advances that could really revolutionize health.The most obvious second step is going from diagnosis to treatment. After all, if you can engineer an organism to respond to a stimuli by producing a dye, it doesn't seem such a dramatic step to respond to the same stimuli with a remedial action. 

         I had the pleasure of meeting Dr Clyde Hutchison III last month. For those who are unfamiliar with Dr Hutchison, he has been involved in a number of extremely notable research projects through the years, including sequencing the first genome (phage phi X174) with Fred Sanger. Now Dr Hutchison is a leading figure in the effort to construct synthetic genomes. Efforts to construct synthetic genomes have been ongoing a long time, for instance I recall discussing this research with a colleague shortly after graduating my BSc (~ 8 years ago). Recent advances by Dr Hutchison and colleagues suggest that this technology may be just around the corner. From there it would seem the logical next step is designer microbial ecosystems.

           Are designer microbiomes then in our future? As crazy as that prospect may seem today, it seems no more crazy than the idea of having cell phones, or video calling, or video calling on a cell phone seemed 30 years ago. Certainly there is a lot of work that has to be done, for one we have to design microbes that are not only fulfill all the beneficial roles currently carried out by our microbiomes (which means we have to elucidate the expanse of those roles), but we have to find ways to create microbes that are both stable and out-compete traditional gut flora. That being said imagine just how revolutionary this would be to health, a gut microbiome that regulated weight, negated pathogens, prevented diseases like IBD, Celiacs disease, perhaps even colon cancer, delivered insulin for diabetics. A vaginal/penile microbiome that prevented STDs, cervical cancer. An oral microbiome that prevented periodontal disease, or even controlled asthma. No more vaccines, no more antibiotics....... I know I'm getting carried away but moving into an age of synthetic genomes presents enormous possibilities and as a young scientist immersed in host-associated microbial ecology I'm excited to be a part of it!!!

Blog 2 Science 1:Commercialization 0

3/4/12

Perhaps the biggest news this week was the shelving of the so-called 'Research Works Act'. The RWA sought to prevent funding agencies, most prominently NIH, requiring fundees to publish their findings in open-access journals. Now don't get me wrong, I'm a fan of freedom of choice but when research is funded with public money surely the public should have free access to it. It is clear that open access journals are the way of the future, they have been around for some time now and proven they are financially viable. They benefit authors through greater exposure and improve scientific quality because they are accessible to all. There is nothing more frustrating to me when seeking scholarly information to come across a title and/or abstract that indicate an answer to my question but when I try to check the evidence having a stupid box pop up telling me I have to pay $30 - $50 just to read the article. Anyway common sense prevailed!! 

Keystone Meeting 2012 - Day 1

3/4/12

Ruslan Medzhitov:

Talked about immunity, or more specifically 'Avoidance', 'Resistance', and 'Tolerance', in an evolutionary sense. For me these were the most interesting points:

* Maximum immune response is not equal to optimal immune response, because the immune response becomes more damaging to self as it becomes more aggresive

* Loss of one form of immune response causes hyper activity of the others (i.e. multiple immune responses are modulatory to each response). This is why immunodeficient individuals often get autoimmune diseases

* Negative pre-conditioning - where exposure to one pathogen enhances virulence of another - the concept is interesting but the only data shown was on co-infection which likely overwhelms the immune system, i.e. there was no actual preconditioning (both pathogens were present at the same time).  

Jeff Gordan:

* Jeff has ~30 Ph.D's / Post-Docs in his arsenal - no wonder he maintains a strong presence in the area (of course it takes some direction also). Its clear from his praise he is a good leader.

* Comparative mammalian metagenomics revealed a switch between amino acid biosynthesis in herbivores to amino acid degradation in carnivores.

* Shows microbiome development over first 17 y of life in a large cohort of North American, South American and Malawi populations. Exponential curve in alpha diversity toward adult microbiome peaking ~1-2y (probably reflects switch from breast/bottle to solid foods).

 - Metagenomically finds enrichment for folate biosynthesis in microbiome in infants and an increase in cobalamin (vit B12) in older children.

 - Genes for starch/arabinoxylan utilization increased in Malawian children.

 * Was able to culture ~50% of the diversity of fecal microbiome by diluting cultures to give ~1 cell / 3 cultures (performed on 96 well plate) - This being a technique pioneered by my good friend Peter Janssen (another great scientist).

Jeff is funded by the Gates foundation for research into malnutrition

Keystone Meeting 2012 - Day 2

Ruth Ley:

Day 2 got off to a great start with Ruth Ley talking about the importance of context in defining the aberrant microbiome. It was the first time I had met Ruth or heard her speak in person and I have to admit she exceeded expectation. Her talk focused on  TLR5 -/- mice and pregnant women who both show increases in fat tissue and inflammation and reductions in insulin sensitivity. But where as one was considered undesirable the other may be an important adaptation. The story behind the TLR5 -/- mice was by far the more intriguing with a nice line of evidence from Unifraq differences in 16S profiles that were indistinguishable, metagenomic profiles that showed functional availability was indifferent but metatranscriptomics revealed increases in the expression of motility genes in the TLR5 -/- mice, and reductions in the expression of CHO metabolic genes. I struggle to make sense of the CHO downreg in the TLR5 -/- mice, but the motility genes were validated using a variety of techniques that revealed increased flagellation in microbial inhabitants and a nice in-vitro study showing E. coli downregs flagellin when abundant resources are available and when anti-flag ab's are introduced.

Rob Knight:

Was as entertaining as always - that good old kiwi sense of humor! He gave a good series of vignettes exhibiting the plethora of research he is involved in over the past few years. I'm not sure I was able to swallow his suggestion that you could get a robust measure delineating microbial ecosystems using just 10 reads per sample. But you have to respect where Prof Knight has been and what he has achieved, here are the points I thought notable:

* The oral cavity is the least variable microbiome, the skin is the most variable

* There are more compositional differences between sites than within sites

* There is more variation between individuals than within an individual

* Samples taken 3 days apart are more similar than samples 3 months apart

Forrest Rohwer:

One of my favorite presenters and one of the most knowledgeable people on viral communities. I had the pleasure of talking to Forrest about his research and my impending move to MSU and unlike some in the field he is a very approachable, enthusiastic and humble individual raising my personal impression of Forrest exponentially. Here are some highlights:

* Viral communities are so diverse, rarefaction analyses on any sampling effort conducted previously has never approached an asymptote

* Healthy human blood is inhabited by a range of viruses

    - Anelloviruses are the most common - present in the blood of all tested animals

* Biogeography in viral distributions in cystic fibrosis lungs (devoid in upper lobe, pleantiful in lower portions)

Colin Hill:

Another great and very friendly researcher from Cork Ireland. I spoke to Collin at dinner and discovered a number of connections: His sisters friend married one of my Ph.D. supervisors, his colleague, another great scientist Paul O'Toole, was one of my undergrad mentors and he used to work with a friend and former colleague of mine Sinead Leahy. His talk provided some great insight into alternative and more defined interventions than fecal transplants in the treatment of  C. difficile infections. The work focused on lactocins (bacteriocins produced by Lactobacillus species. They tested a broad-spectrum lactocin that was, as you may expect, effective but highly perturbing to the mcrobiome, and then a narrow-spectrum lactocin that was able to cure infection without perturbing the residual microbiome.

 

Keystone Meeting 2012 - Day 3

3/6/12

Jeremy Nicholson:

I was very excited about this talk, Prof Nicholson is someone who is really leading the way in microbiome studies as they pertain to health. His talk was great using systems biology approaches to integrate multiple data sources (metabolomics, community composition and disease states) to develop new and powerful insights into disease processes.Highlights:

* A study of ~250,000 people in Europe found 32 genes that were significantly correlated with obesity. These genes collectively explained <1.5 % of the disease (i.e. Genetics is not a major factor in obesity  

* Microbial composition may change slowly but metabolic responses are rapid.

  Prof Nicholson also had a quote that I really liked, highlighting the interdependence between host and microbiome:

"If the microbiome gets sick we feel it, if we get sick the microbiome feels it"

Jens Walter:

The next talk was a late replacement, but contained my moment of the conference. So I talked with Jens after the conference and it was nice to hear he shared similar frustrations at the misinformation permeating through parts of the literature in this area. His talk focused on host-specific adaptations of Lactobacillus reuterii strains. Showing that any strain could colonize a germ free animal, but its ability to out compete other L. reuterii strains or a conventional microbiome and thrive in hosts that are different from its origin are nill. The moment I enjoyed came from a question in response to a statement Jens made regarding the inability of host-derived L. reuterii strains to persist outside of their host (a closed system permitting co-evolution among host and microbe). A member of the audience took great offense at this saying that probiotics disproved all that he was saying (i.e. Lactobacilli grow in yoghurt). Jens responded "yes, but these isolates have never existed in a gut microbiome, instead probiotics manufacturers should target host adapted strains if they want them to be metabollically active and persist" - This fits with a great abundance of data showing the inability of probiotics to colonize a host without prior antibiotic treatment. Other highlights:

* Breast milk contains many carbohydrate components not able to be used by the neonate but are prebiotic (promote beneficial microbiota).   

Thaddeus Stappenbeck:

Works with another researcher I have gotten to know over the years (Eric Martens).

*   In epithelial mucus-production-impaired mice, Bacteroidetes thetaiotiomicron is the most effective at eliciting collitis. A trait shared by many Bacteroidetes sp. and relates to their host glycan forraging capabilities

A Great Time at ABRF

3/22/12

The ABRF conference was a blast, it was great to meet the people that really underpin research advancement. As I stated in my presentation, our research programs depend on them, we expect a lot from them and they always deliver. In return we often forget just how integral they are to our research success. They are the unsung heroes of biological advancement. 

 The talk went well and a small snippet of it found its way into the media (see here) on the genome web site (A site that I did subscribe to before the shout out). I'm also being interviewed tomorrow for Genome Technology - I will post the link when it is available 

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Recent Publications

(16.) Gomez AM, Luckey D, Yeoman CJ, Marietta EV, Berg Miller ME, Murray JA, White BA, Taneja V. (2012) Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible *401 mice but not arthritis-resistant *402 mice. PLoS One In press

(15.) Yeoman CJ. (2012) Simian Metagenomics. In, Encyclopedia of Metagenomics, Animals. Ed. Karen E Nelson (Editor in Chief), Bryan A White, Sarah Highlander, Francisco Rodriguez-Valera (Volume editors). Springer; refworks.springer.com/mrw/index.php?id=3638.

(14.) Berg Miller ME, Yeoman CJ, Chia N, Tringe SG, Edwards RA, Flint HJ, Lamed R, Bayer EA, White BA. (2012) Phage-bacteria relationships and CRISPR elements revealed by a metagenomic survey of the rumen microbiome. Environmental Microbiology 14(1) 207-227

(13.) White BA, Gomez AM, Ho M, Berg Miller M, Thomas S, Yeoman CJ, Yildirim S, Creedon DJ, Goldberg T, Leigh SR, Nelson KE, Stumpf RM, WilsonBA. (2011) Comparative analysis of the vaginal microbiome in health and disease. Genome Biology 11: S1  4

(12.) Brulc JM, Yeoman CJ, Wilson MK, Berg Miller ME, Jeraldo P, Jindou S, Goldenfeld N, Flint HJ, Lamed R, Borovok I, Vodovnik M, Nelson KE, Bayer EA, White BA. (2011) Cellulosomics, a gene-centric approach to investigating the intraspecific diversity and adaptation of Ruminococcus flavefaciens within the rumen. PLoS One 6(10) e25329

(11.) Kabel MA, Yeoman CJ, Han Y, Dodd D, Abbas CA, de Bont JA, Morrison M, Cann IK, Mackie RI. (2011) Biochemical characterization and relative expression levels of multiple carbohydrate esterases by the xylanolytic rumen bacterium Prevotella ruminicola 23 grown on an ester-enriched substrate. Applied and Environmental Microbiology 77(16) 5671-5681

(10.) Amato K, Yeoman CJ, Righini N, Kent A, Estrada A, Munoz D, Stumpf RM, White BA, Nelson KE, Torralba M, Gillis M, Leigh SR. (2011) Gastrointestinal microbial community composition and habitat structure in howler monkeys (Alouatta pigra).  American Journal of Physical Anthropology 144(S52): 75.

(9.) Yildirim S, Rivera AJ, Leigh SR, Yeoman CJ, White BA, GoldbergTL, Wilson BA, Stumpf RM. (2011) Vaginal microbial community structure and maternal ecology in primates. American Journal of Physical Anthropology 144(S52): 315-316.

 (8.) Yeoman CJ, Kelly WJ, Rakonjac J, Leahy SC, Altermann E, Attwood GT. (2011) The large episomes of Butyrivibrio proteoclasticus B316(T) have arisen through intragenomic gene shuttling from the chromosome to smaller Butyrivibrio-specific plasmids. Plasmid 66(2) 67-78

(7.) Yeoman CJ, Chia N, Yildirim S, Berg Miller ME, Kent A, Stumpf R, Leigh SR, Nelson KE, White BA, Wilson BA. (2011) Towards an Evolutionary Model of Animal-Associated Microbiomes. Entropy 13(3) 570 - 594

(6.) Yildirim S, Yeoman CJ, Sipos M, Torralba M, Wilson BA, Goldberg TL, Stumpf RM, Leigh SR, White BA, Nelson KE. (2010) Characterization of the fecal microbiome from non-human wild primates reveals species specific microbial communities. PLoS One 5(11) e13963

(5.) Yeoman CJ, Yildirim S, Thomas SM, Durkin AS, Torralba M, Sutton G, Buhay CJ, Ding Y, Dugan-Rocha SP, Muzny DM, Qin X, Gibbs RA, Leigh SR, Stumpf R, White BA, Highlander SK, Nelson KE, Wilson BA. (2010) Comparative genomics of Gardnerella vaginalis strains reveals substantial differences in metabolic and virulence potential. PLoS One 5( 8 ): e12411 [research applauded at http://f1000.com/10923958]

(4.) Kelly WJ, Leahy SC, Altermann E, Yeoman CJ, Dunne JC, Kong Z, Pacheco DM, Li D, Noel SJ, Moon CD, Cookson AL, Attwood GT. (2010) The glycobiome of the rumen bacterium Butyrivibrio proteoclasticus B316(T) highlights adaptation to a polysaccharide-rich environment. PLoS One 5( 8 ): e11942

(3.) Leahy SC, Kelly WJ, Altermann E, Ronimus RS, Yeoman CJ, Pacheco DM, Li D, Kong Z, McTavish S, Sang C, Lambie SC, Janssen PH, Dey D, Attwood GT. (2010) The genome of the rumen methanogen Methanobrevibacter ruminantium reveals new possibilities for controlling ruminant methane emissions. PLoS One 5(1): e8926

(2.) Yeoman CJ, Han Y, Dodd D, Schroeder CM, Mackie RI, Cann IK. (2010) Thermostable enzymes as biocatalysts in the biofuel industry. Advances in Applied Microbiology 70: 1 - 55

(1.) Brulc JM, Yeoman CJ, Nelson KE, White BA. (2010) Emerging methods in rumen microbiology. Proc. Graz. Livestock Nutr. Conf. Hess BW, DelCurto T, Bowman JGP, Waterman RC. (eds) Proceedings of the Western Section of the American Society of Animal Science.

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