Are Researchers Making the Most of Germ-Free Models?

"All of this indicates that the study of germ-free life has reached a certain maturity."
- James A. Reyniers, 1959
In the years immediately following Reyniers optimistic statement on the maturity of germ-free technology, there was a burst of publications, which leveled off (with oscillations around a value) to a steady stream of activity in the following years. This leveling off indicates that, yes, interest in germ-free mice has matured—growth is happening at the same rate as the general growth of literature in PubMed.

Germ Free Mouse Fraction Chart
Figure 1. Fraction of papers retrieved with the PubMed search—("germ-free" OR gnotobiotic) mice—versus all papers.

At Taconic Biosciences, we think this situation needs to change. And it has everything to do with the microbiome.

Interest in the microbiome has been rapidly increasing (Figure 2) due to a clearer understanding of the microbiome's impact on a number of different physiological systems, as well as a realization that microbial communities can vary widely from person-to-person. A look at recent reviews on microbiome research shows studies on the immune system,2 glucose metabolism, and other metabolic pathways,3 and cancer.4

Given the importance of these systems, we were expecting to see an increase in the number of recent papers published using germ-free mice, but the fraction remains the same (Figure 1). Is this just an artifact of the way we're doing our search? Are researchers only just starting to use more germ-free mice and we'll see an uptick in publications in the coming years? Are researchers not interested in germ-free systems? Or is there just not enough funding right now?

Microbiome Fraction Chart
Figure 2. Fraction of papers retrieved with the PubMed search—microbiome—versus all papers.
  1. J.A. Reyniers. Germ-free vertebrates: present status. Ann NY Acad Sci. 1959. May 8; 78(1):1-16.
  2. P.P. Ahern, et al. Mining the Human Gut Microbiota for Effector Strains that Shape the Immune System. Immunity. 2014 Jun 19; 40(6):815-823.
  3. P.D. Cani, et al. Glucose metabolism: Focus on gut microbiota, the endocannabinoid system and beyond. Diabetes Metab. 2014 Mar 13; pii: S1262-3636(14)00038-X. doi: 10.1016/j.diabet.2014.02.004.
  4. S.J. Bultman. Emerging roles of the microbiome in cancer. Carcinogenesis. 2014 Feb; 35(2):249-55.