Microbial Reprogramming Inhibits Western Diet-Associated Obesity
A recent epidemiological study showed that eating ‘fast food’ items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in t...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2013
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| Online Access: | http://hdl.handle.net/1721.1/80742 https://orcid.org/0000-0001-8294-9364 https://orcid.org/0000-0002-8202-5222 https://orcid.org/0000-0002-8033-8380 https://orcid.org/0000-0003-4378-9542 |
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| author | Poutahidis, Theofilos Kleinewietfeld, Markus Levkovich, Tatiana Bhela, Siddheshvar Chatzigiagkos, Antonis Hafler, David A. Alm, Eric J. Erdman, Susan E. Varian, Bernard Ibrahim, Yassin Lakritz, Jessica Kearney, Sean Michael Smillie, Chris Scott Perrotta, Allison Rose |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Poutahidis, Theofilos Kleinewietfeld, Markus Levkovich, Tatiana Bhela, Siddheshvar Chatzigiagkos, Antonis Hafler, David A. Alm, Eric J. Erdman, Susan E. Varian, Bernard Ibrahim, Yassin Lakritz, Jessica Kearney, Sean Michael Smillie, Chris Scott Perrotta, Allison Rose |
| author_sort | Poutahidis, Theofilos |
| collection | MIT |
| description | A recent epidemiological study showed that eating ‘fast food’ items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in this process. Here we examined human subjects and mouse models consuming Westernized ‘fast food’ diet, and found CD4[superscript +] T helper (Th)17-biased immunity and changes in microbial communities and abdominal fat with obesity after eating the Western chow. In striking contrast, eating probiotic yogurt together with Western chow inhibited age-associated weight gain. We went on to test whether a bacteria found in yogurt may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC 6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy alone was sufficient to change the pro-inflammatory immune cell profile and prevent abdominal fat pathology and age-associated weight gain in mice regardless of their baseline diet. These beneficial microbe effects were transferable into naïve recipient animals by purified CD4[superscript +] T cells alone. Specifically, bacterial effects depended upon active immune tolerance by induction of Foxp3[superscript +] regulatory T cells (Treg) and interleukin (Il)-10, without significantly changing the gut microbial ecology or reducing ad libitum caloric intake. Our finding that microbial targeting restored CD4[superscript +] T cell balance and yielded significantly leaner animals regardless of their dietary ‘fast food’ indiscretions suggests population-based approaches for weight management and enhancing public health in industrialized societies. |
| first_indexed | 2024-09-23T16:11:58Z |
| format | Article |
| id | mit-1721.1/80742 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:11:58Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/807422022-10-02T07:00:10Z Microbial Reprogramming Inhibits Western Diet-Associated Obesity Poutahidis, Theofilos Kleinewietfeld, Markus Levkovich, Tatiana Bhela, Siddheshvar Chatzigiagkos, Antonis Hafler, David A. Alm, Eric J. Erdman, Susan E. Varian, Bernard Ibrahim, Yassin Lakritz, Jessica Kearney, Sean Michael Smillie, Chris Scott Perrotta, Allison Rose Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Varian, Bernard Ibrahim, Yassin Lakritz, Jessica Kearney, Sean Michael Erdman, Susan E. Poutahidis, Theofilos Levkovich, Tatiana Hafler, David A. Alm, Eric J. Smillie, Chris Scott Perrotta, Allison Rose A recent epidemiological study showed that eating ‘fast food’ items such as potato chips increased likelihood of obesity, whereas eating yogurt prevented age-associated weight gain in humans. It was demonstrated previously in animal models of obesity that the immune system plays a critical role in this process. Here we examined human subjects and mouse models consuming Westernized ‘fast food’ diet, and found CD4[superscript +] T helper (Th)17-biased immunity and changes in microbial communities and abdominal fat with obesity after eating the Western chow. In striking contrast, eating probiotic yogurt together with Western chow inhibited age-associated weight gain. We went on to test whether a bacteria found in yogurt may serve to lessen fat pathology by using purified Lactobacillus reuteri ATCC 6475 in drinking water. Surprisingly, we discovered that oral L. reuteri therapy alone was sufficient to change the pro-inflammatory immune cell profile and prevent abdominal fat pathology and age-associated weight gain in mice regardless of their baseline diet. These beneficial microbe effects were transferable into naïve recipient animals by purified CD4[superscript +] T cells alone. Specifically, bacterial effects depended upon active immune tolerance by induction of Foxp3[superscript +] regulatory T cells (Treg) and interleukin (Il)-10, without significantly changing the gut microbial ecology or reducing ad libitum caloric intake. Our finding that microbial targeting restored CD4[superscript +] T cell balance and yielded significantly leaner animals regardless of their dietary ‘fast food’ indiscretions suggests population-based approaches for weight management and enhancing public health in industrialized societies. National Institutes of Health (U.S.) (Grant P30-ES002109) National Institutes of Health (U.S.) (Grant RO1CA108854) National Institutes of Health (U.S.) (Grant P01 AI045757) National Institutes of Health (U.S.) (Grant U19 AI046130) National Institutes of Health (U.S.) (Grant U19 AI070352) National Institutes of Health (U.S.) (Grant P01 AI039671) National Institute of Neurological Disorders and Stroke (U.S.) (Jacob Javits Merit Award NS2427) The Penates Foundation Nancy Taylor Foundation for Chronic Diseases, Inc. 2013-09-16T15:01:22Z 2013-09-16T15:01:22Z 2013-07 2013-04 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/80742 Poutahidis, Theofilos, Markus Kleinewietfeld, Christopher Smillie, Tatiana Levkovich, Alison Perrotta, Siddheshvar Bhela, Bernard J. Varian, et al. “Microbial Reprogramming Inhibits Western Diet-Associated Obesity.” Edited by Laurel L. Lenz. PLoS ONE 8, no. 7 (July 10, 2013): e68596. https://orcid.org/0000-0001-8294-9364 https://orcid.org/0000-0002-8202-5222 https://orcid.org/0000-0002-8033-8380 https://orcid.org/0000-0003-4378-9542 en_US http://dx.doi.org/10.1371/journal.pone.0068596 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Poutahidis, Theofilos Kleinewietfeld, Markus Levkovich, Tatiana Bhela, Siddheshvar Chatzigiagkos, Antonis Hafler, David A. Alm, Eric J. Erdman, Susan E. Varian, Bernard Ibrahim, Yassin Lakritz, Jessica Kearney, Sean Michael Smillie, Chris Scott Perrotta, Allison Rose Microbial Reprogramming Inhibits Western Diet-Associated Obesity |
| title | Microbial Reprogramming Inhibits Western Diet-Associated Obesity |
| title_full | Microbial Reprogramming Inhibits Western Diet-Associated Obesity |
| title_fullStr | Microbial Reprogramming Inhibits Western Diet-Associated Obesity |
| title_full_unstemmed | Microbial Reprogramming Inhibits Western Diet-Associated Obesity |
| title_short | Microbial Reprogramming Inhibits Western Diet-Associated Obesity |
| title_sort | microbial reprogramming inhibits western diet associated obesity |
| url | http://hdl.handle.net/1721.1/80742 https://orcid.org/0000-0001-8294-9364 https://orcid.org/0000-0002-8202-5222 https://orcid.org/0000-0002-8033-8380 https://orcid.org/0000-0003-4378-9542 |
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