Laura C. Bridgewater

Diet, Gut Microbiome, and Mental Health Interactions

Dietary patterns affect the composition of the gut microbiota, and a growing body of
evidence suggests that the gut microbiota can influence mental health by means of connections
between the enteric nervous system and the brain. As this project proceeded, anxiety emerged
as the primary focus of our behavioral studies as it seemed to be most responsive to dietary
changes in our mouse models. We purchased a video tracking and analysis software system with
capital equipment funds (not from this MEG), and designed the following behavioral testing
arenas and mazes which have been constructed by the BYU Instrument Shop: open field arena,
elevated plus maze, open slopes tests, marble burying test, and three-chamber social interaction
arena. My students have developed expertise in administering all of these tests and are
continuing to collect data on the way diet affects both anxiety behaviors and the composition of
the gut microbiota. We have also added a new angle to the study—inducing autism in mouse
pups by maternal immune activation and then testing the ability of dietary changes to alter the
gut microbiota and anxiety behaviors. This project is ongoing with at least two publications still
in the data collection phase, as well as the publications listed below from studies that are
completed. We have developed new expertise in the bioinformatic analysis of 16S metagenomic
DNA sequencing data, and we are continuing to develop new strengths in this area. I expect that
this new research focus on diet, the gut microbiota, and anxiety will be a major focus of research
in my lab for the forseeable future.
Below are lists of papers published and of posters presented at scientific meetings, which
have resulted from mentoring in my lab since this MEG grant was awarded in 2014. BYU student
authors are in bold to emphasize the number of students who have benefited from mentoring in
the Bridgewater Lab.

Publications
1. Bridgewater, L.C., Zhang, C., Wu, Y., Hu, W., Zhang, Q., Wang, J., Li, S., Zhao, L. “Genderbased
differences in host behavior and gut microbiota composition in response to high fat
diet and stress in a mouse model.” (under review at the ISME Journal).

2.

Cordner, R.D., Friend

, L.N., Mayo, D., Badgley, C., Wallmann, J.L., Stallings, C., Young, P.,
Miles, A., Edwards, J.G., & Bridgewater, L.C. “The BMP2 nuclear variant, nBMP2, is
expressed in mouse hippocampus and impacts memory.” (under review at Scientific
Reports).

3.

Beatty, A.

, Bowden, A.E., Bridgewater, L.C. “Design and validation of a complex loading
whole spinal segment bioreactor.” Journal of Biomechanical Engineering, in press (2016).

4. Long, W., Xue, Z., Zhang, Q., Feng, Z., Bridgewater, L.C., Wang, L., Zhao, L., Pang, X.
“Differential responses of gut microbiota to the same prebiotic formula in oligotrophic
and eutrophic batch fermentation systems.” Scientific Reports 5:13469 doi:
10.1038/srep13469 http://www.nature.com/articles/srep13469 (2015).

5.

Olsen, D.S., Goar, W.A., Nichols, B.A., Bailey, K.T.

, Christensen, S. L., Merriam, K.R.,
Reynolds, P.R., Wilson, E., Weber, K.S., Bridgewater, L.C. “Targeted mutation of nuclear
bone morphogenetic protein 2 (nBMP2) impairs secondary immune response in a mouse
model.” BioMed Research International vol. 2015, Article ID 975789,
doi:10.1155/2015/975789 http://www.hindawi.com/journals/bmri/2015/975789/
(2015).

6. Zhang, C., Yin, A., Li, H., Wang, R., Wu, G., Shen, J., Zhang, M., Wang, L., Hou, Y., Ouyang,
H., Zhang, Y., Zheng, Y., Wang, J., Lv, X., Wang, Y., Zhang, F., Zeng, B., Li, W., Yan, F., Zhao,
Y., Pang, X., Zhang, X., Fu, H., Chen, F., Zhao, N., Hamaker, B.R., Bridgewater, L.C.,
Weinkove, D., Clement, K., Dore, J., Holmes, E., Xiao, H., Zhao, G., Yang, S., Bork, P.,
Nicholson, J.K., Wei, H., Tang, H., Zhang, X., Zhao, L. “Dietary modulation of gut
microbiota contributes to alleviation of both genetic and simple obesity in children.”
EBioMedicine 2:966-982. http://dx.doi.org/10.1016/j.ebiom.2015.07.007 (2015).

7.

Stolworthy, D.K.

, Bowden, A.E., Roeder, B.L., Robinson, T.F.,

Holland, J.G., Christensen, S.L., Beatty, A.M.

, Bridgewater, L.C., Eggett, D.L., Wendel, J.D., Stieger-Vanegas, S. “MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.”
Journal of Orthopaedic Research http://onlinelibrary.wiley.com/doi/10.1002/jor.22968/full (2015).

8. Xue, Z., Zhang, W., Wang, L., Hou, R., Zhang, M., Fei, L., Zhang, X., Huang, H., Bridgewater,
L., Jiang, Y., Jiang, C., Zhao, L., Pang, X., and Zhang, Z.
“The bamboo-eating giant panda harbors a carnivore-like gut microbiota, with excessive
seasonal variations.” mBio 6:3, doi: 10.1128/mBio.00022-15
http://mbio.asm.org/content/6/3/e00022-15.full (2015).

9. Chen, H., Liu, Y., Zhang, M., Wang, G., Qi, Z., Bridgewater, L.C., Zhao, L., Tang, Z, Pang, X.
“A Filifactor alocis-centered co-occurrence group associates with periodontitis across
different oral habitats.” Scientific Reports 5:9053, doi: 10.1038/srep09053
http://www.nature.com/articles/srep09053 (2015).

10.

Stolworthy, D.K., Fullwood, R.A., Merrell, T.M.

, Bridgewater, L.C., & Bowden, A.E.
“Biomechanical comparison of the camelid and human intervertebral disc.” Journal of
Orthopaedic Translation 3:34-43, http://dx.doi.org/10.1016/j.jot.2014.12.001 (2014).

Posters

1. Bowden, A.E., Beatty, A.M., Bridgewater, L.C. “Design and validation of a complex
loading whole spinal segment bioreactor.” Philadelphia Spine Research Symposium, held
in conjunction with the Orthopaedic Research Society. Philadelphia, Pennsylvania (2015).

2. Hancock, J., Cook, M., Grose, J., Bridgewater, L.C., and Weber, K.S. “Role of PAS kinase
and metabolism on immune cells.” Autumn Immunology Conference. Chicago, Illinois
(2015).

3. Rees, A., Franson, J., White, J., Ong, K.L., Choksi, N., Hilton, A., Grose, J., and
Bridgewater, L.C. “The role of PAS kinase and the gut microbiome in metabolism and
diabetes onset in mice. American Society for Microbiology. New Orleans, Louisiana
(2015).

4. Yates, J.D. Bridgewater, L.C. “Evidence for a nuclear variant of decapentaplegic (dpp).”
Southwest Regional Meeting of the Society for Developmental Biology. Aurora, Colorado
(2014).

5. Mayo, J.L., Nichols, B.A., Olsen, D.S., Cordner, R.D., Hancock, C.R., Weber, K.S., Wilson,
E., Edwards, J.G., Barrow, J.R., and Bridgewater, L.C. “The nBMP2 mutant mouse shows
defects in intracellular calcium transport-regulated pathways.” Southwest Regional
Meeting of the Society for Developmental Biology. Aurora, Colorado (2014).

Summary of Spending

The budget for this project was spent as follows:
• Animal care costs, LSB mouse facility ($10,000)
• PCR enzymes and primers for genotyping the mice ($2,000)
• High fat/high sugar diet ($1600)
• Screw-capped test tubes for storing fecal samples ($400)
• Student wages ($6000)