Gut flora

from Teresa Binstock

http://www.sciencedaily.com/releases/2011/04/110419214734.htm

This study used a single high dose of streptomycin orally in one arm, and low doses of several antibiotics in drinking water in another arm. The results are quite dramatic:

"The most profoundly altered pathways involved steroid hormones, eicosanoid hormones, sugar, fatty acid, and bile acid"

Antibiotics Disrupt Gut Ecology, Metabolism

ScienceDaily (Apr. 19, 2011) — Humans carry several pounds of microbes in our gastro-intestinal tracts. Recent research suggests that this microbial ecosystem plays a variety of critical roles in our health. Now, working in a mouse model, researchers from Canada describe many of the interactions between the intestinal microbiota and host, and show that antibiotics profoundly disrupt intestinal homeostasis. The research is published in the April 2011 issue of the journal Antimicrobial Agents and Chemotherapy.

"Intestinal microbes help us digest our food, provide us with vitamins that we cannot make on our own, and protect us from microbes that make us sick, amongst other things," says L Caetano M. Antunes of the University of British Columbia, a researcher on the study. In this study, the investigators used powerful mass spectrometry techniques to detect, identify, and quantify more than two thousand molecules which they extracted from mouse feces. They then administered antibiotics to the mice, to kill off most of their gut microbiota, and analyzed the feces anew.

The second round of mass spectroscopy revealed a very different metabolic landscape. The levels of 87 percent of the molecules detected had been shifted up or down by factors ranging from 2-fold to 10,000-fold.

The most profoundly altered pathways involved steroid hormones, eicosanoid hormones, sugar, fatty acid, and bile acid. "These hormones have very important functions in our health," says Antunes. "They control our immune system, reproductive functions, mineral balance, sugar metabolism, and many other important aspects of human metabolism."

The findings have two important implications, says Antunes. "First, our work shows that the unnecessary use of antibiotics has deleterious effects on human health that were previously unappreciated. Also, the fact that our gut microbes control these important molecules raises the possibility that manipulating these microbes could be used to modulate diseases that have hormonal or metabolic origins (such as inmmunodeficiency, depression, diabetes and others). However, further studies will be required to understand exactly how our microbial partners function to modulate human physiology, and to devise ways of using this information to improve human health."

(L.C.M. Antunes, J. Han, R.B.R. Ferreira, P. Lolic, C.H. Borchers, and B.B. Finlay, 2011. Effect of antibiotic treatment on the intestinal metabolome. Antim. Agents Chemother. 55:1494-1503.)
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Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by American Society for Microbiology, via EurekAlert!, a service of AAAS.

Journal Reference:

L. C. M. Antunes, J. Han, R. B. R. Ferreira, P. Lolic, C. H. Borchers, B. B. Finlay. Effect of Antibiotic Treatment on the Intestinal Metabolome. Antimicrobial Agents and Chemotherapy, 2011; 55 (4): 1494 DOI: 10.1128/AAC.01664-10

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Antimicrobial Agents and Chemotherapy, April 2011, p. 1494-1503, Vol. 55, No. 4
0066-4804/11/$12.00+0 doi:10.1128/AAC.01664-10
Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Effect of Antibiotic Treatment on the Intestinal Metabolome

L. Caetano M. Antunes,1 Jun Han,2 Rosana B. R. Ferreira,1 Petra Loli

,1,3 Christoph H. Borchers,2, and B. Brett Finlay1,3*

Michael Smith Laboratories, The University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada,1 University of Victoria Genome BC Proteomics Centre, University of Victoria, Victoria, British Columbia V8Z 7X8, Canada,2 Department of Microbiology and Immunology, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada3

Received 1 December 2010/ Returned for modification 8 January 2011/ Accepted 21 January 2011

The importance of the mammalian intestinal microbiota to human health has been intensely studied over the past few years. It is now clear that the interactions between human hosts and their associated microbial communities need to be characterized in molecular detail if we are to truly understand human physiology. Additionally, the study of such host-microbe interactions is likely to provide us with new strategies to manipulate these complex systems to maintain or restore homeostasis in order to prevent or cure pathological states. Here, we describe the use of high-throughput metabolomics to shed light on the interactions between the intestinal microbiota and the host. We show that antibiotic treatment disrupts intestinal homeostasis and has a profound impact on the intestinal metabolome, affecting the levels of over 87% of all metabolites detected. Many metabolic pathways that are critical for host physiology were affected, including bile acid, eicosanoid, and steroid hormone synthesis. Dissecting the molecular mechanisms involved in the impact of beneficial microbes on some of these pathways will be instrumental in understanding the interplay between the host and its complex resident microbiota and may aid in the design of new therapeutic strategies that target these interactions.