Friday, February 13, 2015

Unwanted effect of Antibiotic (ab)use - Effect on mitochrondrial gene expression!

Contributed by: Dr. Akilesh Ramasamy & Dr. Tamhankar

Antibiotic use has a profound influence on the gut flora. It's a well known effect. But a recent study reveals the effects could be more devastating and far reaching than previously known.
"Just in the past decade a whole new universe has opened up about the far-reaching effects of antibiotic use, and now we're exploring it. The study of microbiota is just exploding. Nothing we find would surprise me at this point." Prof. Morgan
Prof. Audrey Morgan and his colleagues have found that antibiotics have effect on many other things apart from the endogenous microflora. They seem to affect glucose metabolism, the immune system, food digestion and behaviour. They also suspect it is linked to obesity and stress. The researchers used the mouse model of microbiota depletion by a cocktail of antibiotics in this study.

Some of the alarming results they found apart from the direct effect of antibiotics on the gut microflora were:

  1. Antibiotics kill intestinal epithelium cells directly.
  2. Antibiotics inhibited mitochondrial gene expression.
Quoting the "result" section from their article abstract:
We found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments.
1: Morgun A, Dzutsev A, Dong X, Greer RL, Sexton DJ, Ravel J, Schuster M, Hsiao W, Matzinger P, Shulzhenko N. Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks. Gut. 2015 Jan 22. pii:gutjnl-2014-308820. doi: 10.1136/gutjnl-2014-308820. PMID: 25614621.

2. medicalnewstoday carries a feature about this study as well.