Ketogenic Diet-Associated Worsening of Osteoarthritis Histologic Secerity- Increased Pain Sensitivity and Gut Microbiome Dysbiosis in Mice

Authors
Gabby Dyson, Montana Barrett, Leoni Schlupp, Emmaline Prinz, Nicholas Hannebut, Aleksander Szymczak, Cindy Miranda Brawner, Matlock A. Jeffries


Lab

Journal
ACR Open Rheumatology

Abstract
Our laboratory has compiled mouse gut microbiome data sets relating to OA in the context of sex and MRL/B6 transplantation12,13; when we compare our current findings to these data sets we identified 31 overlaps (Supplementary Table3). Among these, 25 were of concordant direction (with respect to OA outcome or OA risk) and 6 were discordant; for example, classCoriobacterialeswas decreased with KD in both DMM and sham mice and was also decreased in male animals versus female controls (in our sex-microbiome study) and in B6 mice compared to MRL mice (in our MRL-B6 transplantation study). Thus, we now have evidence from three independent observational/interventional mouse OA studies that specific gut microbiome clades are consistently correlated with improved OA outcomes (Coriobacteriia,Lactobacillales,Burkholderiales), whereas certain clades are correlated with worsened OA outcomes (Bacteroidaceae,Dehalobacteriaceae). Furthermore, in our present microbiome analysis we found all microbiome clades (n = 8) that were significantly correlated both with histology and mechanical allodynia were of concordant direction; that is, positively correlated with histology and allodynia (evidenced by negative correlation with withdrawal threshold). Finally, although our current study was not designed to detect gut microbiome changes induced by DMM compared to sham surgery, we nonetheless did find 11 clade differences in KD and 9 clade differences in chow-fed mice that were altered in DMM. Of these, eight overlapped between the two diets, and all of these were in concordant direction (Staphylococcusincreased in DMM,Clostridialesand variousProteobacteriareduced in DMM; Figure4B); this is the first evidence of gut microbiome changes occurring with OA development in the DMM model. Taken together, this body of data suggests that the gut microbiome in general and these clades in particular may play a bona fide role in OA development in mice.

Keywords/Topics
diet; pain

BIOSEB Instruments Used:
SMALGO: SMall animal ALGOmeter - Wireless (BIO-SMALGO-WRS)

Source :

https://acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/acr2.11794

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