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CeMbio - The C. elegans microbiome resource

Philipp Dirksen, Adrien Assié, Johannes Zimmermann, Fan Zhang, Adina-Malin Tietje, Sarah Arnaud Marsh, Marie-Anne Félix, Michael Shapira, Christoph Kaleta, Hinrich Schulenburg, Buck S. Samuel

Preprint posted on 24 April 2020 https://www.biorxiv.org/content/10.1101/2020.04.22.055426v1

Article now published in G3: Genes|Genomes|Genetics at http://dx.doi.org/10.1534/g3.120.401309

Are your C. elegans fed up of eating E. coli? Get the CeMbio kit and give them the good stuff. Check out the new preprint from Dirksen, Assié and colleagues to find out about the C. elegans microbiome resource.

Selected by Miguel V. Almeida

Categories: microbiology

 

Background

The song that goes “you’ll never walk alone” got it absolutely right. No multicellular organism exists in a vacuum. We are literally never walking alone, as we carry on us, and within us, an enormous number of other organisms, a majority of which are bacteria. Altogether, these comprise the microbiome, an important component influencing our development and physiology. Dissection of microbiome-host interactions is highly complex, due to the difficulty of controlling for distinct effects of genetics and environment for both hosts and microbiota. Recent studies have revealed the composition of the natural gut microbiome of the popular nematode model organism Caenorhabditis elegans. With these new insights, and combined with a great diversity of genetic tools and easiness of manipulation, C. elegans is becoming a fascinating animal system for microbiome studies. An important step is reported in a recent preprint by Dirksen, Assié and colleagues, describing CeMbio, the C. elegans microbiome resource.

 

Key findings

  • First, the authors selected 12 bacteria strains representative of the natural elegans microbiome. These strains encompass the diversity of bacteria colonizing the C. elegans gut and are easy to grow and maintain in laboratory conditions.
  • Then, they verified that these strains are able to colonize the gut of elegans separately and in combination (as a community). Also, the authors described gut colonization dynamics using two C. elegans strains and distinct plating conditions.
  • Comparisons of developmental rate of elegans animals grown on different bacteria showed that worms grew faster when fed with the community of CeMbio bacterial strains versus E. coli OP50. Individually, CeMbio strains promoted distinct growth dynamics: nine strains promoted faster growth than OP50, one strain similar growth, and two strains slower growth. This demonstrates that CeMbio strains are beneficial for their host as a community, when compared to commonly used E. coli, but have distinct effects on their host individually.
  • To provide as complete a resource as possible, the authors sequenced the genomes of the CeMbio strains, with a combination of short- and long-read sequencing. Subsequent 16S rRNA phylogenies allowed the identification of the bacterial species in 8/12 strains, and of the bacterial genera in the remaining four strains. The genomic information also informed on the metabolic competences of the CeMbio strains.

 

What I like about this preprint

Microbiome research is a bit off my main research interests, but I do find it fascinating. I came to know about this preprint a couple of days before it was posted online, by attending Buck Samuel’s talk at the recent TAGC 2020 online conference*. I got immediately hooked. I like that this resource, the result of a highly collaborative effort involving several labs (Samuel, Félix, Schulenburg, and Shapira), is made for the C. elegans community. Not only microbiome researchers will benefit from this work. With access to these strains (available from the Caenorhabditis Genetics Center), experimental protocols for colonization, and whole-genome sequences, researchers can now test, in a streamlined manner, whether their favorite biological paradigm is influenced in any way by the microbiome. Many crucial aspects of how host‑microbial interactions regulate host health and disease can now be tested in C. elegans, with the CeMbio resource.

 

Open questions

  • The effect of the CeMbio bacteria strains on host developmental rate was measured in this work. However, fecundity is also a critical measure of fitness. Did you quantify the brood sizes of elegans animals grown with the CeMbio community (in combination and separately)? This could prove an important measure to ensure that germline development is not compromised.
  • Model organisms adapt to laboratory growth conditions. It’s fascinating to me that N2 worms grown for so many generations in the lab, feeding on OP50, have no problem going back to their natural archetypal microbiome and even grow better in most of these CeMbio strains. Can you comment on this plasticity? How come the development of N2 strains is positively affected by CeMbio strains, although N2 animals haven’t encountered these bacteria for thousands of generations?
  • The principal component analysis of metabolic profiles of BiGb0170 and JUb44, the bacteria strains which promoted slower developmental rate, are similar. What do you think they have in common that affects elegans development?

 

Want to know more?

Caenorhabditis elegans responses to bacteria from its natural habitats, Samuel et al., 2016

https://www.pnas.org/content/113/27/E3941.short

 

Host-Specific Functional Significance of Caenorhabditis Gut Commensals, Berg et al., 2016

https://www.frontiersin.org/articles/10.3389/fmicb.2016.01622/full

 

The native microbiome of the nematode Caenorhabditis elegans: gateway to a new host-microbiome model, Dirksen et al., 2016

https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0258-1

 

Caenorhabditis elegans as a Model for Microbiome Research, Zhang et al., 2017

https://www.frontiersin.org/articles/10.3389/fmicb.2017.00485/full

 

 

*TAGC2020 online was a very successful experiment. TAGC 2020 organizers swiftly turned what was a huge conference in an even bigger virtual conference. And for free! Many thanks to GSA for organizing! A list of preprints discussed at TAGC2020 available here: https://prelights.biologists.com/prelists/tagc-2020/

 

Tags: bacteria, c. elegans, cembio, microbiome, resource, synthetic communities

Posted on: 14 May 2020 , updated on: 15 May 2020

doi: https://doi.org/10.1242/prelights.20648

Read preprint (1 votes)

Author's response

Hinrich Schulenburg & Buck Samuel shared

 

Hinrich Schulenburg:

Here is a brief reply to your questions. Buck may add some more information.

1) Worm brood size and/or worm population growth rate has been assessed in the presence of some of the CeMBio bacteria and also some mixtures. Part of these results are published in the early papers from our groups. In general, both characteristics increased on CeMBio bacteria, but not on all. These two characteristics clearly deserve further assessment and this is something that can now be done with the CeMBio resource.

2) Based on the current data, we cannot really say why N2 is still able to benefit from naturally associated microbes, even though it should have adapted to a life without a microbiome. A more detailed understanding of this aspect could be obtained by exploring variation in the response of N2 versus more recent natural isolates of C. elegans to these bacteria. Several labs are indeed currently looking into this.

3) Again, it is imppossible to say with only the current data at hand what is causing the lower developmental rate on BiGb0170 and JUb44. This is one of many aspects that can now be studied with the CeMBio resource. This is one of the reasons why we developed this resource: To encourage research of this fantastic model organism in the presence of its microbiome and thus a more natural context than that used in most current studies.

 

Buck Samuel:

Thanks again for the highlight and I agree with the responses that Hinrich has provided, and would just add a couple points.

The main goal of this resource was not to answer all of the questions, but really to provide a foundation that places this robust model system in a more natural (microbial) context.  There almost certainly are differences among the microbes that have bearing on any aspect of C. elegans biology, including reproduction. Similarly, the role of the Bacteroidetes (JUb44 and BIGb0170) could result from absence of a key metabolite given their more limited complements of (known) metabolic pathways, by production of some as yet to be recognized unique metabolites that delay growth or some completely different way. We previously noted that mixing JUb44 with as little as 5% of an Enterobacteriaceae tempers most of the growth delay [Samuel, PNAS 2016]. So, the real fun begins when we as researchers and as a community move beyond binary microbe-by-host interactions and embrace the complexity of microbiomes. This is where the exciting discoveries to be made!

 

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