PERSPECTIVES

MICROBIOLOGY Intestinal bacteria from lean humans can confer protection against fat gain in Fighting Obesity with Bacteria experimental mice. Alan W. Walker and Julian Parkhill

he human large intestine harbors a with reduced adiposity, did not reduce adi- The findings support some emerging complex community of microorgan- posity in the Obch mice. This indicates that hypotheses regarding potential mechanisms Tisms (microbiota) that affect many more complex bacterial interactions underlie by which the microbiota can affect host aspects of our physiology and health (1 ). protection against increased body mass and weight gain. One of the main activities of the Numerous lines of evidence, particularly associated metabolic disturbance. intestinal microbiota is to break down and from rodent models, have suggested that the Ridaura et al. also identifi ed diet as an ferment dietary fi bers into short-chain fatty intestinal microbiota may play a role in the important factor in the transmission of micro- acids (SCFAs) such as acetate, propionate, development of obesity. On page 1079 of biota and associated host phenotype. Lean and butyrate. The host absorbs these acids, this issue, Ridaura et al. ( 2) demonstrate that twin–derived bacterial strains effectively and humans obtain perhaps 5 to 10% of daily the microbiota from lean or obese humans colonized and ameliorated excess adiposity energy requirements from them ( 3). Ridaura induces similar phenotypes in mice and, more in Obch mice when the recipients were fed a et al. show that the microbiota in Ln mice remarkably, that the microbiota from lean low-fat, high-fi ber diet. This was not the case produces greater amounts of SCFAs, partic- donors can invade and reduce adiposity gain when the mice were fed a diet that was high in ularly propionate and butyrate, and digests in the obese-recipient mice if the mice are fed saturated fat but low in fi ber. more of the plant fi ber present in the mouse’s an appropriate diet. Ridaura et al. recruited four human A female twin pairs discordant for obesity and transferred the intestinal microbiota in fecal on March 6, 2015 samples from each of them into the intestines Low-fat, of germ-free mice. Animals receiving a trans- high-fiber diet plant from the obese (Ob) twin donors devel- oped increased adiposity compared to those Increased adiposity Microbiota Recipient mice receiving transplants from lean (Ln) twin Obese twin transplant donors. Differences in mouse adiposity could also be reproduced after inoculation of germ-

free mice with collections of cultured bacte- www.sciencemag.org ria grown from twin-pair fecal samples. Co- Low-fat, housing of mice harboring cultured bacteria high-fiber diet from an obese twin (Obch) with mice harbor- Lean ing cultured bacteria from a lean twin (Lnch) Lean twin prevented the development of increased adi- posity in the Obch mice. This occurred in tan- B dem with successful colonization of Obch intestines by bacteria from the Lnch mice. By Downloaded from contrast, Obch microbes did not transmit to Lnch mice, and these animals remained lean. This indicated that transmissibility of intesti- nal microbes and adiposity phenotype were Low-fat, high-fiber diet Ineffective tightly linked. mici robbioti a Analysis of the bacterial communities transmiissiono showed that members of the Bacteroidetes phylum, particularly Bacteroides spp., could pass from the Lnch mice and colonize the Obch mice, suggesting that these bacteria were High-fat,low-fiber diet Ineffectivee largely responsible for protection against microbiota increased adiposity. However, cohousing of transmission Obch mice with lean mice inoculated with a relatively simple mix of just 39 defi ned bac- Please pass the microbiota. (A) Germ-free mice inoculated with microbiota from obese or lean human twins SCIENCE terial strains, including many of the Bacteroi- take on the microbiota characteristics of the donor. Those receiving the obese microbiota (red outline) had des species that were previously correlated an increase in adiposity, whereas those receiving the lean microbiota (blue outline) remained lean. (B) If fed an appropriate diet, mice harboring the obese microbiota, when cohoused with mice harboring the lean Group, Sanger Insti- microbiota, are invaded by the lean microbiota and do not develop increased adiposity (blue and red tute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, outline). By contrast, the obese microbiota does not effectively colonize mice harboring the lean microbiota,

CREDIT: V. ALTOUNIAN/ V. CREDIT: UK. E-mail: [email protected] and these mice remain lean.

www.sciencemag.org SCIENCE VOL 341 6 SEPTEMBER 2013 1069 Published by AAAS PERSPECTIVES

diet than the microbiota of Ob mice. Thus, individuals consuming diets high in fiber to the recipient. The mouse model presented increased weight gain in Ob mice does not compared to Europeans consuming typical by Ridaura et al. is therefore timely, as it result from increased energy harvest. Rather, Western diets (11 ). Given these potential dis- offers the potential to test human-derived the fi nding supports previous studies showing crepancies, it will be important to verify in bacterial strains, and accompanying dietary that although SCFAs are a source of energy, humans the activity of bacteria that are ben- regimens, within a controlled mammalian they promote leanness by inhibiting fat accu- efi cial in mouse models. host environment. The study is a step toward mulation in adipose tissue, raising energy Perhaps the most intriguing finding of the ultimate goal of developing relatively expenditure, and enhancing production of Ridaura et al. is that microbial protection simple mixtures of bacteria for testing as hormones associated with feelings of satiety from increased adiposity is only possible anti-obesity therapeutics. ( 4– 6). Other putative mechanisms include a against the backdrop of a suitable host diet. role for the microbiota in metabolizing bile It may be that future microbiota-based thera- References acids, branched-chain amino acids, and acyl- pies for an obese individual will require an 1. A. W. Walker, T. D. Lawley, Pharmacol. Res. 69, 75 (2013). carnitines, which have all been linked to alteration in diet to aid colonization by ben- 2. V. K. Ridaura et al., Science 341, 1241214 (2013); either insulin resistance or obesity in humans efi cial microbes. This offers a potentially syn- DOI: 10.1126/science.1241214. and mice. ergistic approach, whereby reduced caloric 3. L. V. Hooper, T. Midtvedt, J. I. Gordon, Annu. Rev. Nutr. 22, 283 (2002). A key question is the translatability of the intake and increased fi ber consumption not 4. I. Kimura et al., Nat. Commun. 4, 1829 (2013). fi ndings to a human clinical context. Bacte- only have a positive impact on energy bal- 5. Z. Gao et al., Diabetes 58, 1509 (2009). roides species, correlated with reduced adi- ance but might also promote transplanted 6. M. J. Keenan et al., Obesity (Silver Spring) 14, 1523 (2006). posity by Ridaura et al., have repeatedly been microbial communities that are associated 7. P. J. Turnbaugh et al., 444, 1027 (2006). implicated in protection against obesity in with leanness. 8. S. H. Duncan et al., Int. J. Obes. 32, 1720 (2008). mice (7 ). However, evidence from human Fecal transplants in humans have been 9. A. Schwiertz et al., Obesity (Silver Spring) 18, 190 studies is mixed (8 ). Indeed, Bacteroides, used to benefi cially alter the microbiota in (2010). 10. G. D. Wu et al., Science 334, 105 (2011). and the propionate that they produce, can be a variety of ailments ( 12). Notably, a recent 11. C. De Filippo et al., Proc. Natl. Acad. Sci. U.S.A. 107, more abundant in overweight and obese indi- study showed that fecal transplants from lean 14691 (2010). viduals than in lean counterparts (9 ). Further- individuals into obese counterparts improved 12. E. van Nood et al., N. Engl. J. Med. 368, 407 (2013). more, Bacteroides have been associated with insulin sensitivity in some obese recipients 13. A. Vrieze et al., Gastroenterology 143, 913, e7 (2012). diets high in animal protein and saturated fats (13 ). The procedure is not risk free, however, (10 ) and are notably reduced in lean African with the potential for introducing 10.1126/science.1243787

GEOPHYSICS

How can a higher level of earthquake prepared- Reducing Earthquake Risk ness be achieved, particularly in developing nations? Brian E. Tucker

he preceding Perspectives in this and incorporating the results of Earth science differences in urban population growth (see series (1 – 4) provide snapshots of the and earthquake engineering research into the fi gure) and the quality of seismic-resis- T earthquake and tsunami risks, haz- post-earthquake reconstruction. The United tant construction (9 – 11). Why is progress so ard monitoring and risk mitigation activities, Nations (UN) International Strategies for frustratingly slow? and current research Disaster Reduction questions concerning serves as a platform The Importance of Being Prepared some of the world’s to coordinate these One reason is that historically, far fewer seismic hot spots— efforts and, through resources have been invested in pre-earth- South Central Asia, its Hyogo Frame- quake preparedness and risk reduction than the Caribbean, Tur- work for Action, has in post-earthquake response, reconstruction, key, Tokyo, and San- declared the goal “to and recovery; this is particularly true in devel- tiago. The image that substantially reduce oping countries. One study (12 ) suggests that emerges is one of disaster losses by of all international aid for humanitarian assis- considerable progress in reducing losses due 2015 by building the resilience of nations and tance, less than 10% is directed to disaster pre- to earthquakes and tsunamis in some places communities to disasters” ( 5). vention; a more recent study ( 13) estimates but of growing and evolving risks in others. Despite these diverse and sustained that this fi gure is only 1%. Post-disaster activ- In the past two decades, the prevailing efforts, human and economic losses due to ities are important and reliably garner gener- approach to reducing the consequences of earthquakes are increasing and are projected ous support among individuals, governments, earthquakes and tsunamis has emphasized to continue to rise in the future (6 , 7). The and nonprofi t organizations, appealing to the raising awareness of these hazards, promot- past decade (2001 to 2012) saw more than human impulse to help those in need. Yet a ing methods of reducing their associated risk, three times as many earthquake-related comparison of the consequences of recent deaths as the preceding two decades (1981 to earthquakes in developing countries, where GeoHazards International, 687 Bay Road, Menlo Park, CA 2000) (8 ). These losses are increasingly con- preparedness is rare, and industrialized coun- 94025, USA. E-mail: [email protected] centrated in developing countries because of tries, where it is much more common, sug-

1070 6 SEPTEMBER 2013 VOL 341 SCIENCE www.sciencemag.org Published by AAAS Fighting Obesity with Bacteria Alan W. Walker and Julian Parkhill Science 341, 1069 (2013); DOI: 10.1126/science.1243787

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