TY - JOUR
T1 - Age matters
T2 - Microbiome depletion prior to repeat mild traumatic brain injury differentially alters microbial composition and function in adolescent and adult rats
AU - Sgro, Marissa
AU - Iacono, Giulia
AU - Yamakawa, Glenn R.
AU - Kodila, Zoe N.
AU - Marsland, Benjamin J.
AU - Mychasiuk, Richelle
N1 - Funding Information:
This work was supported by grants from the National Health and Medical Research Council (NHMRC) to Richelle Mychasiuk (#1173565) and Benjamin Marsland (#1154344) as well as a fellowship from the Victorian Endowment for Science, Knowledge, and Innovation (VESKI) to Benjamin Marsland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022 Sgro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/11
Y1 - 2022/11
N2 - Dysregulation of the gut microbiome has been shown to perpetuate neuroinflammation, alter intestinal permeability, and modify repetitive mild traumatic brain injury (RmTBI)induced deficits. However, there have been no investigations regarding the comparative effects that the microbiome may have on RmTBI in adolescents and adults. Therefore, we examined the influence of microbiome depletion prior to RmTBI on microbial composition and metabolome, in adolescent and adult Sprague Dawley rats. Rats were randomly assigned to standard or antibiotic drinking water for 14 days, and to subsequent sham or RmTBIs. The gut microbiome composition and metabolome were analysed at baseline, 1 day after the first mTBI, and at euthanasia (11 days following the third mTBI). At euthanasia, intestinal samples were also collected to quantify tight junction protein (TJP1 and occludin) expression. Adolescents were significantly more susceptible to microbiome depletion via antibiotic administration which increased pro-inflammatory composition and metabolites. Furthermore, RmTBI induced a transient increase in ‘beneficial bacteria’ (Lachnospiraceae and Faecalibaculum) in only adolescents that may indicate compensatory action in response to the injury. Finally, microbiome depletion prior to RmTBI generated a microbiome composition and metabolome that exemplified a potentially chronic pathogenic and inflammatory state as demonstrated by increased Clostridium innocuum and Erysipelatoclostridium and reductions in Bacteroides and Clostridium Sensu Stricto. Results highlight that adolescents are more vulnerable to RmTBI compared to adults and dysbiosis prior to injury may exacerbate secondary inflammatory cascades.
AB - Dysregulation of the gut microbiome has been shown to perpetuate neuroinflammation, alter intestinal permeability, and modify repetitive mild traumatic brain injury (RmTBI)induced deficits. However, there have been no investigations regarding the comparative effects that the microbiome may have on RmTBI in adolescents and adults. Therefore, we examined the influence of microbiome depletion prior to RmTBI on microbial composition and metabolome, in adolescent and adult Sprague Dawley rats. Rats were randomly assigned to standard or antibiotic drinking water for 14 days, and to subsequent sham or RmTBIs. The gut microbiome composition and metabolome were analysed at baseline, 1 day after the first mTBI, and at euthanasia (11 days following the third mTBI). At euthanasia, intestinal samples were also collected to quantify tight junction protein (TJP1 and occludin) expression. Adolescents were significantly more susceptible to microbiome depletion via antibiotic administration which increased pro-inflammatory composition and metabolites. Furthermore, RmTBI induced a transient increase in ‘beneficial bacteria’ (Lachnospiraceae and Faecalibaculum) in only adolescents that may indicate compensatory action in response to the injury. Finally, microbiome depletion prior to RmTBI generated a microbiome composition and metabolome that exemplified a potentially chronic pathogenic and inflammatory state as demonstrated by increased Clostridium innocuum and Erysipelatoclostridium and reductions in Bacteroides and Clostridium Sensu Stricto. Results highlight that adolescents are more vulnerable to RmTBI compared to adults and dysbiosis prior to injury may exacerbate secondary inflammatory cascades.
UR - http://www.scopus.com/inward/record.url?scp=85143180399&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0278259
DO - 10.1371/journal.pone.0278259
M3 - Article
C2 - 36449469
AN - SCOPUS:85143180399
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 11
M1 - e0278259
ER -