Arquivo da tag: Obesidade

O peso através das gerações (Pesquisa Fapesp)

Entre ratos, efeitos do consumo excessivo ou da falta de comida podem ser transmitidos para filhos e netos 

REINALDO JOSÉ LOPES | ED. 252 | FEVEREIRO 2017

Experimentos com ratos feitos por pesquisadores de universidades de São Paulo reforçam a ideia de que o excesso de peso pode ser um fenômeno que transcende gerações – e não apenas porque os filhos tendem a herdar dos pais genes que favorecem o acúmulo de energia e os tornam predispostos à obesidade ou porque vivem em um ambiente com disponibilidade excessiva de comida. Alterações na oferta de alimento para as fêmeas um pouco antes ou durante a gravidez parecem aumentar, por mecanismos ainda pouco compreendidos, a probabilidade de que tenham filhos e até netos com sobrepeso.

Em uma série de testes, a bióloga Maria Martha Bernardi e sua equipe na Universidade Paulista (Unip) alimentaram algumas ratas no início da vida reprodutiva e outras já grávidas com uma dieta bastante calórica e aguardaram para ver o que acontecia com a primeira geração de filhotes e também com os filhos desses filhotes. Tanto os roedores que nasceram de mães superalimentadas quanto os da geração seguinte apresentaram mais predisposição a desenvolver sobrepeso.

A tendência de ganho excessivo de peso ocorreu mesmo quando os filhos e os netos dessas ratas foram alimentados apenas com a dieta padrão de laboratório. Segundo Martha, esses resultados indicam que o período em que o feto está se desenvolvendo no útero é crucial para definir a regulação do metabolismo do animal e, ao menos, o da geração seguinte.

Se essas mudanças aparecessem apenas na primeira geração, o mais natural seria imaginar que alterações hormonais provocadas pela dieta materna teriam afetado os filhotes. Como o efeito avança até a segunda geração, os pesquisadores suspeitam que a propensão a ganhar peso seja mantida por mecanismos epigenéticos: alterações no padrão de ativação e desligamento dos genes provocadas por fatores ambientais, como a dieta, e transmitidas às gerações seguintes. Essas mudanças no perfil de acionamento dos genes não alteram diretamente a sequência de “letras químicas” do DNA, apesar de serem herdadas através das gerações. Embora o grupo de Martha não tenha analisado o padrão de atividade dos genes, dados obtidos por cientistas mundo afora indicam que mudanças no perfil de ativação gênica sem alteração na sequência de DNA podem acontecer tanto em animais quanto em seres humanos.

Dieta que engorda
Curiosamente, não foi só a superalimentação materna durante a gestação que parece ter mexido com o perfil de ativação de seus genes e deixado filhos e netos com tendência a engordar. Em um dos experimentos, realizado em parceria com pesquisadores das universidades de São Paulo (USP), Federal do ABC (UFABC) e Santo Amaro (Unisa), 12 fêmeas de ratos receberam 40% menos comida do que o considerado normal para as roedoras prenhes, enquanto oito ratas do grupo de controle foram alimentadas com a dieta habitual de laboratório.

As fêmeas que passaram fome durante a gestação ganharam menos da metade do peso das ratas que puderam comer à vontade. Os filhotes das mães submetidas à restrição alimentar nasceram menores e continuaram mais magros durante algum tempo, ainda que recebessem a mesma quantidade de comida que os filhos das ratas que não passaram fome. Só na idade adulta a diferença desapareceu e os dois grupos de roedores alcançaram peso semelhante, embora os filhos das ratas famintas apresentassem uma proporção maior de gordura corporal – em especial, de uma forma de gordura que se acumula entre os órgãos (gordura visceral), associada a maior risco de problemas cardiovasculares.

A diferença mais importante surgiu na segunda geração. Os netos de ratas que haviam comido pouco enquanto estavam prenhes nasceram menores, mas, depois de adultos, eram um pouco (de 10% a 15%) mais pesados que os netos das ratas alimentadas normalmente. Eles tinham mais gordura visceral e também sinais de inflamação no cérebro. Esse ganho extra de peso ocorreu mesmo com as fêmeas da primeira geração, portanto, mães desses animais, tendo sido alimentadas normalmente. É como se a privação de alimento experimentada pelas ratas da geração inicial provocasse uma reprogramação metabólica duradoura em seus descendentes, afirmam os pesquisadores em artigo publicado em maio de 2016 na revista Reproduction, Fertility and Development.

O trabalho da equipe paulista, nesse ponto, confirma pesquisas anteriores que já haviam encontrado uma associação entre episódios de fome na gravidez e o nascimento de filhos com propensão ao aumento de peso e aos problemas de saúde a ele associados. Embora não tenham identificado o mecanismo específico por trás desse efeito, Martha Bernardi e sua equipe suspeitam que compostos produzidos pelo organismo das mães da geração inicial, parcialmente privadas de comida na gestação, ativem genes que favorecem o rápido ganho de peso no filhote. Assim, os sinais químicos emitidos pelo corpo materno funcionariam como um alerta de que o ambiente é de escassez e que é preciso usar com máxima eficiência os recursos alimentares disponíveis. Essa sinalização recebida pelo organismo do filhote poderia fazer toda a diferença, representando a chance de crescer e sobreviver em um ambiente com privação de alimento. “Mas também pode levar à obesidade, caso a oferta de alimentos volte a se normalizar depois que ele nasce”, explica Martha.

Estudos realizados nas décadas anteriores mostraram uma situação muito parecida com a descrita acima entre os descendentes das mulheres que ficaram grávidas durante o chamado Hongerwinter (inverno da fome, em holandês), quando os exércitos nazistas que recuavam na Holanda diante do avanço dos Aliados cortaram boa parte do transporte de suprimentos para o país entre o fim de 1944 e o começo de 1945, no final da Segunda Grande Guerra. Tanto os filhos quanto os netos das sobreviventes do Hongerwinter apresentavam taxas de obesidade e problemas metabólicos acima do esperado para a população geral.

Inflamação no cérebro
Em outro estudo, Martha e seus colegas forneceram alimentação hipercalórica – uma mistura de ração padrão mais um suplemento líquido rico em diferentes tipos de gordura – para 10 ratas logo após o desmame, enquanto outro grupo de fêmeas recebeu a alimentação normal e serviu de controle. Conforme o esperado, as ratas submetidas à dieta hipercalórica quando bebês ficaram acima do peso, ainda que não obesas, ao chegar à puberdade. Efeitos semelhantes foram observados em suas filhas: eram ratas que, quando adultas, apresentaram sobrepeso e alterações metabólicas, como o acúmulo de gordura visceral, embora tenham sido tratadas apenas com uma dieta balanceada durante toda a vida. Também publicado na Reproduction, Fertility and Development, esse trabalho e outros estudos do grupo indicam que o sobrepeso foi o desencadeador de processos inflamatórios que afetaram o cérebro da mãe e da prole, de forma aparentemente duradoura.

Se parece estranho imaginar que o excesso de peso pode levar a uma inflamação cerebral, é preciso lembrar que as células de gordura não são meros depósitos de calorias. Os adipócitos, como são chamados, produzem uma grande variedade de substâncias, entre as quais moléculas desencadeadoras de inflamações, que chegam à corrente sanguínea e, a partir dela, ao hipotálamo, região do cérebro associada, entre outras funções, ao controle da fome.

Trabalhos do grupo da Unip ainda não publicados indicam ainda que essa inflamação pode atingir outras áreas cerebrais dos roedores. A hipótese dos pesquisadores é de que o processo inflamatório no órgão esteja ligado à reprogramação do organismo transmitida da mãe para os filhotes, incluindo aí alterações no controle do apetite que podem se manter durante a vida adulta.

Para Alicia Kowaltowski, pesquisadora do Instituto de Química da USP que estuda a relação entre a dieta e os mecanismos de produção de energia das células, é bastante forte a possibilidade de que a tendência ao sobrepeso e à obesidade seja passada de uma geração para outra por meios que não envolvem a herança de genes favorecedores do ganho de peso. “A questão é saber quais são os mecanismos que estão por trás desses fenômenos”, conta a pesquisadora.

Entre tais mecanismos, um candidato que tem ganhado força são as transformações epigenéticas. O prefixo grego epi significa superior, e na palavra epigenética, cunhada nos anos 1940 pelo embriologista inglês Conrad Waddington, designa a área da biologia que estuda as modificações químicas motivadas pelo ambiente que levam à ativação ou inativação dos genes e alteram o funcionamento do organismo. Uma das modificações químicas mais comuns e simples sofrida pelos genes é a chamada metilação. Nela, um grupo metila, formado por um átomo de carbono e três de hidrogênio (CH3), acopla-se a um trecho de DNA, impedindo que ele seja lido pelo maquinário da célula. O resultado é o silenciamento daquela região. Estudos com dezenas de espécies de animais, plantas e fungos já mostraram que o perfil de metilação pode ser transmitido de uma geração para outra e afetar as características da prole.

Influência paterna
O papel das mães no sobrepeso dos filhos parece cada vez mais sólido. E quanto ao papel do pai? “Há alguns indícios de que a influência paterna também pode ocorrer, mas eles são menos claros”, diz Martha Bernardi. Por um lado, faz sentido que influências epigenéticas possam ser transmitidas pelo lado paterno – assim como outras células do organismo, os espermatozoides podem ser afetados por alterações no padrão de ativação dos genes produzidas por influência do ambiente. Se tais mudanças não forem totalmente eliminadas após o encontro entre as células sexuais masculinas e os óvulos, o novo indivíduo gerado pela fecundação poderia carregar parte da memória epigenética de seu pai.

Um estudo de 2015, feito por uma equipe da Universidade de Copenhague, na Dinamarca, e liderado por Romain Barrès, mostrou que esse cenário é plausível ao estudar os espermatozoides de 16 homens obesos e outros 10 com peso normal. No caso dos voluntários obesos, os padrões epigenéticos, como os de metilação, concentravam-se em genes ligados ao desenvolvimento do sistema nervoso, em especial os que são importantes para o controle do apetite (e, portanto, do peso), o que não ocorria com os homens magros.

Barrès e seus colegas fizeram outra comparação sugestiva entre as marcações epigenéticas dos espermatozoides dos obesos antes da cirurgia de redução de estômago e as desses mesmos participantes após a operação. Resultado: depois da cirurgia, o padrão epigenético das células lembrava o de homens com peso normal.

“O mais importante a respeito dessas descobertas é sugerir que tais modificações podem ocorrer em células germinativas, ou seja, os óvulos e espermatozoides, e ser transmitidas para gerações seguintes”, diz o médico Licio Augusto Velloso, professor da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (FCM-Unicamp), que estuda os mecanismos celulares e moleculares ligados à origem da obesidade e do diabetes. “Os estudos epigenéticos avançaram muito na última década e se espera que, num futuro não muito distante, o mapeamento de fatores ambientais e de seu impacto em diferentes aspectos da epigenética nos ajude a prevenir doenças importantes”, afirma Velloso.

Enxergar o excesso de peso pelo prisma epigenético pode trazer mais uma peça relevante para o quebra-cabeça da epidemia global de obesidade e de doenças metabólicas ligadas a ela. Historicamente associado à saúde e à fartura, o excesso de peso se tornou um problema de grandes proporções primeiro nos países ricos, mas hoje é cada vez mais comum em países mais pobres – a começar pelo Brasil, onde quase 60% da população adulta está acima do peso considerado saudável, conforme dados do Instituto Brasileiro de Geografia e Estatística (IBGE). Muitos países em desenvolvimento passaram rapidamente de um contexto em que a desnutrição era um problema grave para outro em que a obesidade é muito mais preocupante.

Artigos científicos
JOAQUIM, A. O. et al. Maternal food restriction in rats of the F0 generation increases retroperitoneal fat, the number and size of adipocytes and induces periventricular astrogliosis in female F1 and male F2 generationsReproduction, Fertility and Development. 31 mai. 2016.
JOAQUIM, A. O. et alTransgenerational effects of a hypercaloric dietReproduction, Fertility and Development. 25 ago. 2015.

Anúncios

How altered gut microbes cause obesity (Science Daily)

Date:
June 8, 2016
Source:
Yale University
Summary:
Obesity is linked to changes in our gut microbes — the trillions of tiny organisms that inhabit our intestines. But the mechanism has not been clear to date. In a new study, a team of researchers has identified how an altered gut microbiota causes obesity.

Obesity is linked to changes in our gut microbes — the trillions of tiny organisms that inhabit our intestines. But the mechanism has not been clear. In a new study published in Nature, a Yale-led team of researchers has identified how an altered gut microbiota causes obesity.

In an earlier study, Gerald I. Shulman, M.D., the George R. Cowgill Professor of Medicine, observed that acetate, a short-chain fatty acid, stimulated the secretion of insulin in rodents. To learn more about acetate’s role, Shulman, who is also an investigator of the Howard Hughes Medical Institute, and a team of Yale researchers conducted a series of experiments in rodent models of obesity.

The research team compared acetate to other short-chain fatty acids and found higher levels of acetate in animals that consumed a high-fat diet. They also observed that infusions of acetate stimulated insulin secretion by beta cells in the pancreas, but it was unclear how.

Next, the researchers determined that when acetate was injected directly into the brain, it triggered increased insulin by activating the parasympathetic nervous system. “Acetate stimulates beta cells to secrete more insulin in response to glucose through a centrally mediated mechanism,” said Shulman. “It also stimulates secretion of the hormones gastrin and ghrelin, which lead to increased food intake.”

Finally, the research team sought to establish a causal relationship between the gut microbiota and increased insulin. After transferring fecal matter from one group of rodents to another, they observed similar changes in the gut microbiota, acetate levels, and insulin.

“Taken together these experiments demonstrate a causal link between alterations in the gut microbiota in response to changes in the diet and increased acetate production,” said Shulman. The increased acetate in turn leads to increased food intake, setting off a positive feedback loop that drives obesity and insulin resistance, he explained.

The study authors suggest that this positive feedback loop may have served an important role in evolution, by prompting animals to fatten up when they stumbled across calorically dense food in times of food scarcity.

“Alterations in the gut microbiota are associated with obesity and the metabolic syndrome in both humans and rodents,” Shulman noted. “In this study we provide a novel mechanism to explain this biological phenomenon in rodents, and we are now examining whether this mechanism translates to humans.”


Journal Reference:

  1. Rachel J. Perry, Liang Peng, Natasha A. Barry, Gary W. Cline, Dongyan Zhang, Rebecca L. Cardone, Kitt Falk Petersen, Richard G. Kibbey, Andrew L. Goodman, Gerald I. Shulman. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndromeNature, 2016; 534 (7606): 213 DOI: 10.1038/nature18309

What’s the Beef? (Slate)

No, “Meatless Monday” is not an evil vegetarian plot to deprive our children of precious steak, pork, and chicken.

Photo by Debbi Morello/Getty Images

First-grader Christina Muse, pictured on Oct. 15, 2002, at North Hampton School in New Hampshire, taunts the meat industry by eating cheese pizza. Photo by Debbi Morello/Getty Images

The meat industry has a serious case of the Mondays. A growing number of school districts, including ones in Los Angeles, San Diego, and Miami, are committing to keep meat off the menu for one day a week to combat childhood obesity. These “Meatless Monday” initiatives have drawn the ire of America’s beef, poultry, and pork interests, which see them as the first, flesh-free volley in a war against America’s meat peddlers. The less-meat movement has also proved to be a flashpoint for elected officials, namely those from farm states, who seem to be placing the economic interests of their home-state industries above the health and wellbeing of their states’ populaces.

This story played out somewhat quietly on the national stage several years ago, when a few grandstanding politicians caught wind of an interoffice newsletter at the U.S. Department of Agriculture suggesting employees consider eating less meat. Now, it’s getting more attention at the local level. This week Todd Staples, the head of Texas’ Agriculture Department, unleashed a blistering—if largely fact-free—jeremiad against the Meatless Monday movement after learning that it had been enacted by elementary schools in Dripping Springs, an Austin suburb. (He was apparently unaware that several schools in Houston have been experimenting with the idea for some time.) “Restricting children’s meal choice to not include meat is irresponsible and has no place in our schools,” Staples wrote inan op-ed published by the Austin American-Statesman. “This activist movement called ‘Meatless Monday’ is a carefully orchestrated campaign that seeks to eliminate meat from Americans’ diets seven days a week—starting with Mondays.” Dun dun DUN!

An elected official like Staples can, of course, stake out a position that aligns with a particular industry without simply being a mouthpiece for it. But the agriculture commissioner’s overblown rhetoric echoes the official company line of the meat industry, which has filled his campaign coffers with at least $116,000 since 2010, according to public records. It’s hard to fault meat producers for wanting people to eat more meat. It’s a different story, though, when someone like Staples spouts such talking points at a time when the nation is battling both an obesity epidemic and a global climate crisis—two problems driven, at least in part, by resource-intensive meat production.

In some corners of the country, neither of those concerns is seen as much of a reason to impose mandates from above. The irony here is that the Dripping Springs initiative is a local one—the very type of decision that small-government advocates say is under attack from the national school-lunch standards championed by Michelle Obama. “Are we having a war on meat in Dripping Springs? Definitely not,” John Crowley, the head of nutrition services for the school district, told a local CBS affiliate this week. “We’re trying to think outside the box, and we serve a lot of Texas beef on our menus. We’ve had requests for more vegetarian options, and I thought, ‘Why don’t I give it a try and see how it’s received by kids?’ ”

This is a message that kids should be receiving. According to the 2011 National Survey of Children’s Health, nearly one-third of American kids are either overweight or obese, a classification linked to Type 2 diabetes and myriad other health problems. The meat industry, meanwhile, is one of the top contributors to climate change, with the United Nations estimating that it directly or indirectly produces about 14.5 percent of the world’s anthropogenic greenhouse gas emissions. Everyone from the American Heart Association to the Norwegian military has touted the health and environmental benefits of eating less meat.

Such endorsements mean little to Staples and his meat-minded allies, who either downplay or downright deny the benefits of curbing meat consumption. But their dire warnings of The End of Meat aside, their argument also fails on a smaller scale. Opponents routinely overlook the fact that meatless meals are not by definition protein-free, a claim at the heart of Staples’ op-ed. “It is important to remember that for many underprivileged children the meals they eat at school often represents their best meals of the day,” the Republican commissioner wrote. “To deprive them of a meat-based protein during school lunch is most likely depriving them of their only source of protein for the day.”

That makes no sense given that Meatless Monday menus include items like bean-and-cheese burritos and cheese pizza, meals that come with a hefty serving of protein—and, thanks to dairy, animal protein at that. Meanwhile, the national school lunch program requires schools to offer a weekly menu that meets a minimum threshold for protein, so a Dripping Springs student who goes meatless on Monday is in little danger of being protein-deprived come Friday. Kids who want a ham sandwich, meanwhile, are still welcome to bring one from home—and there are obviously no restrictions on what a child can eat outside school. The participating cafeterias, meanwhile, continue to serve up a variety of meats the rest of the week.

Following Staples’ logic will take you to an absurd place. If a lunch menu is an edict from on high as he suggests, then when a cafeteria serves a hamburger but not a hot dog, it is “forcing” kids to eat beef while “denying” them pork—or any number of food items not on that particular day’s menu, for that matter, be it chicken, fish, or atarragon shallot egg salad sandwich with a side of butternut squash soup with chestnuts.

As commissioner, Staples oversees the agency that administers the school lunch programs in his state. There appears to be little he can do, at least formally, to stop the cafeterias’ Meatless Mondays from spreading their steak-free sentiments across the rest of Texas. “As long as [the schools] follow the requirements of the National School Lunch Program, they can serve anything they want,” says Humane Society of the United States food policy director Eddie Garza, who worked with the Dripping Springs cafeterias to implement the program. “Staples doesn’t have any real weight on this other than writing op-eds.”

While Staples’ formal power may be limited, his industry allies have managed to score meaty victories in the past. Last summer they managed to squash a small-scale Meatless Monday program in Capitol Hill cafeterias in a matter of days by branding it “an acknowledged tool of animal rights and environmental organizations who seek to publicly denigrate U.S. livestock and poultry production.”

One of their more notable wins came in 2012, after the U.S. Department of Agriculture published that interoffice newsletter. It read, in part: “One simple way to reduce your environmental impact while dining at our cafeterias is to participate in the ‘Meatless Monday’ initiative.” The backlash from the industry—and the backtracking from the agency that followed—was strong and instantaneous. Almost immediately after the National Cattlemen’s Beef Association publicly voiced its anger, farm-state lawmakers like Iowa Republicans Chuck Grassley and Steve King scrambled to fall in line. Sen. Grassley tweeted, “I will eat more meat on Monday to compensate for stupid USDA recommendation [about] a meatless Monday.” Rep. King was even more specific with his plan, promising to stage his own “double rib-eye Mondays” in protest. “With extreme drought conditions plaguing much of the United States, the USDA should be more concerned about helping drought-stricken producers rather than demonizing an industry reeling from the lack of rain,” Kansas Republican Sen. Jerry Moran told Agriculture Secretary Tom Vilsack in a statementthat appeared all the more short-sighted given the realities of climate change.

Before the day was out, the newsletter was taken offline, and the USDA issued a statement saying that it “does not endorse Meatless Monday.” The newsletter—which also offered a variety of other small-scale energy-efficiency tips for agency employees—“was posted without proper clearance,” according to the department.

Unwilling to forgive and forget, Staples chimed in by calling for the employee who wrote the newsletter to be fired, calling the very suggestion that people eat less meat “treasonous.” “Last I checked,” Staples said then, “USDA had a very specific duty to promote and champion American agriculture. Imagine Ford or Chevy discouraging the purchase of their pickup trucks. Anyone else see the absurdity? How about the betrayal?”

That type of twisted logic only works in a world where agriculture officials serve the food industry and not the American public. Unfortunately, that feels like it’s the case all too often.

Josh Voorhees is a Slate senior writer. He lives in Iowa City.

The Fat Drug (New York Times)

By PAGAN KENNEDY

MARCH 8, 2014

CreditJing Wei

IF you walk into a farm-supply store today, you’re likely to find a bag of antibiotic powder that claims to boost the growth of poultry and livestock. That’s because decades of agricultural research has shown that antibiotics seem to flip a switch in young animals’ bodies, helping them pack on pounds. Manufacturers brag about the miraculous effects of feeding antibiotics to chicks and nursing calves. Dusty agricultural journals attest to the ways in which the drugs can act like a kind of superfood to produce cheap meat.

But what if that meat is us? Recently, a group of medical investigators have begun to wonder whether antibiotics might cause the same growth promotion in humans. New evidence shows that America’s obesity epidemic may be connected to our high consumption of these drugs. But before we get to those findings, it’s helpful to start at the beginning, in 1948, when the wonder drugs were new — and big was beautiful.

That year, a biochemist named Thomas H. Jukes marveled at a pinch of golden powder in a vial. It was a new antibiotic named Aureomycin, and Mr. Jukes and his colleagues at Lederle Laboratories suspected that it would become a blockbuster, lifesaving drug. But they hoped to find other ways to profit from the powder as well. At the time, Lederle scientists had been searching for a food additive for farm animals, and Mr. Jukes believed that Aureomycin could be it. After raising chicks on Aureomycin-laced food and on ordinary mash, he found that the antibiotics did boost the chicks’ growth; some of them grew to weigh twice as much as the ones in the control group.

Mr. Jukes wanted more Aureomycin, but his bosses cut him off because the drug was in such high demand to treat human illnesses. So he hit on a novel solution. He picked through the laboratory’s dump to recover the slurry left over after the manufacture of the drug. He and his colleagues used those leftovers to carry on their experiments, now on pigs, sheep and cows. All of the animals gained weight. Trash, it turned out, could be transformed into meat.

You may be wondering whether it occurred to anyone back then that the powders would have the same effect on the human body. In fact, a number of scientists believed that antibiotics could stimulate growth in children. From our contemporary perspective, here’s where the story gets really strange: All this growth was regarded as a good thing. It was an era that celebrated monster-size animals, fat babies and big men. In 1955, a crowd gathered in a hotel ballroom to watch as feed salesmen climbed onto a scale; the men were competing to see who could gain the most weight in four months, in imitation of the cattle and hogs that ate their antibiotic-laced food. Pfizer sponsored the competition.

In 1954, Alexander Fleming — the Scottish biologist who discovered penicillin — visited the University of Minnesota. His American hosts proudly informed him that by feeding antibiotics to hogs, farmers had already saved millions of dollars in slop. But Fleming seemed disturbed by the thought of applying that logic to humans. “I can’t predict that feeding penicillin to babies will do society much good,” he said. “Making people larger might do more harm than good.”

Nonetheless, experiments were then being conducted on humans. In the 1950s, a team of scientists fed a steady diet of antibiotics to schoolchildren in Guatemala for more than a year,while Charles H. Carter, a doctor in Florida, tried a similar regimen on mentally disabled kids. Could the children, like the farm animals, grow larger? Yes, they could.

Mr. Jukes summarized Dr. Carter’s research in a monograph on nutrition and antibiotics: “Carter carried out a prolonged investigation of a study of the effects of administering 75 mg of chlortetracycline” — the chemical name for Aureomycin — “twice daily to mentally defective children for periods of up to three years at the Florida Farm Colony. The children were mentally deficient spastic cases and were almost entirely helpless,” he wrote. “The average yearly gain in weight for the supplemented group was 6.5 lb while the control group averaged 1.9 lb in yearly weight gain.”

Researchers also tried this out in a study of Navy recruits. “Nutritional effects of antibiotics have been noted for some time” in farm animals, the authors of the 1954 study wrote. But “to date there have been few studies of the nutritional effects in humans, and what little evidence is available is largely concerned with young children. The present report seems of interest, therefore, because of the results obtained in a controlled observation of several hundred young American males.” The Navy men who took a dose of antibiotics every morning for seven weeks gained more weight, on average, than the control group.

MEANWHILE, in agricultural circles, word of the miracle spread fast. Jay C. Hormel described imaginative experiments in livestock production to his company’s stockholders in 1951; soon the company began its own research. Hormel scientists cut baby piglets out of their mothers’ bellies and raised them in isolation, pumping them with food and antibiotics. And yes, this did make the pigs fatter.

Farms clamored for antibiotic slurry from drug companies, which was trucked directly to them in tanks. By 1954, Eli Lilly & Company had created an antibiotic feed additive for farm animals, as “an aid to digestion.” It was so much more than that. The drug-laced feeds allowed farmers to keep their animals indoors — because in addition to becoming meatier, the animals now could subsist in filthy conditions. The stage was set for the factory farm.

 Credit Jing Wei

And yet, scientists still could not explain the mystery of antibiotics and weight gain. Nor did they try, really. According to Luis Caetano M. Antunes, a public health researcher at the Oswaldo Cruz Foundation in Brazil, the attitude was, “Who cares how it’s working?” Over the next few decades, while farms kept buying up antibiotics, the medical world largely lost interest in their fattening effects, and moved on.

In the last decade, however, scrutiny of antibiotics has increased. Overuse of the drugs has led to the rise of antibiotic-resistant strains of bacteria — salmonella in factory farms and staph infections in hospitals. Researchers have also begun to suspect that it may shed light on the obesity epidemic.

In 2002 Americans were about an inch taller and 24 pounds heavier than they were in the 1960s, and more than a third are now classified as obese. Of course, diet and lifestyle are prime culprits. But some scientists wonder whether there could be other reasons for this staggering transformation of the American body. Antibiotics might be the X factor — or one of them.

Martin J. Blaser, the director of the Human Microbiome Program and a professor of medicine and microbiology at New York University, is exploring that mystery. In 1980, he was the salmonella surveillance officer for the Centers for Disease Control and Prevention, going to farms to investigate outbreaks. He remembers marveling at the amount of antibiotic powder that farmers poured into feed. “I began to think, what is the meaning of this?” he told me.

Of course, while farm animals often eat a significant dose of antibiotics in food, the situation is different for human beings. By the time most meat reaches our table, it contains little or no antibiotics. So we receive our greatest exposure in the pills we take, rather than the food we eat. American kids are prescribed on average about one course of antibiotics every year, often for ear and chest infections. Could these intermittent high doses affect our metabolism?

To find out, Dr. Blaser and his colleagues have spent years studying the effects of antibiotics on the growth of baby mice. In one experiment, his lab raised mice on both high-calorie food and antibiotics. “As we all know, our children’s diets have gotten a lot richer in recent decades,” he writes in a book, “Missing Microbes,” due out in April. At the same time, American children often are prescribed antibiotics. What happens when chocolate doughnuts mix with penicillin?

The results of the study were dramatic, particularly in female mice: They gained about twice as much body fat as the control-group mice who ate the same food. “For the female mice, the antibiotic exposure was the switch that converted more of those extra calories in the diet to fat, while the males grew more in terms of both muscle and fat,” Dr. Blaser writes. “The observations are consistent with the idea that the modern high-calorie diet alone is insufficient to explain the obesity epidemic and that antibiotics could be contributing.”

The Blaser lab also investigates whether antibiotics may be changing the animals’ microbiome — the trillions of bacteria that live inside their guts. These bacteria seem to play a role in all sorts of immune responses, and, crucially, in digesting food, making nutrients and maintaining a healthy weight. And antibiotics can kill them off: One recent study found that taking the antibiotic ciprofloxacin decimated entire populations of certain bugs in some patients’ digestive tracts — bacteria they might have been born with.

Until recently, scientists simply had no way to identify and sort these trillions of bacteria. But thanks to a new technique called high-throughput sequencing, we can now examine bacterial populations inside people. According to Ilseung Cho, a gastroenterologist who works with the Blaser lab, researchers are learning so much about the gut bugs that it is sometimes difficult to make sense of the blizzard of revelations. “Interpreting the volume of data being generated is as much a challenge as the scientific questions we are interested in asking,” he said.

Investigators are beginning to piece together a story about how gut bacteria shapes each life, beginning at birth, when infants are anointed with populations from their mothers’ microbiomes. Babies who are born by cesarean and never make that trip through the birth canal apparently never receive some key bugs from their mothers — possibly including those that help to maintain a healthy body weight. Children born by C-section are more likely to be obese in later life.

By the time we reach adulthood, we have developed our own distinct menagerie of bacteria. In fact, it doesn’t always make sense to speak of us and them. You are the condo that your bugs helped to build and design. The bugs redecorate you every day. They turn the thermostat up and down, and bang on your pipes.

In the Blaser lab and elsewhere, scientists are racing to take a census of the bugs in the human gut and — even more difficult — to figure out what effects they have on us. What if we could identify which species minimize the risk of diabetes, or confer protection against obesity? And what if we could figure out how to protect these crucial bacteria from antibiotics, or replace them after they’re killed off?

The results could represent an entirely new pharmacopoeia, drugs beyond our wildest dreams: Think of them as “anti-antibiotics.” Instead of destroying bugs, these new medicines would implant creatures inside us, like more sophisticated probiotics.

Dr. Cho looks forward to this new era of medicine. “I could say, ‘All right, I know that you’re at risk for developing colon cancer, and I can decrease that risk by giving you this bacteria and altering your microbiome.’ That would be amazing. We could prevent certain diseases before they happened.”

Until then, it’s hard for him to know what to tell his patients. We know that antibiotics change us, but we still don’t know what to do about it. “It’s still too early to draw definitive conclusions,” Dr. Cho said. “And antibiotics remain a valuable resource that physicians use to fight infections.”

When I spoke to Mr. Antunes, the public health researcher in Brazil, he told me that his young daughter had just suffered through several bouts of ear infections. “It’s a no-brainer. You have to give her antibiotics.” And yet, he worried about how these drugs might affect her in years to come.

It has become common to chide doctors and patients for overusing antibiotics, but when the baby is wailing or you’re burning with fever, it’s hard to know what to do. While researchers work to unravel the connections between antibiotics and weight gain, they should also put their minds toward reducing the unnecessary use of antibiotics. One way to do that would be to provide patients with affordable tests that give immediate feedback about what kind of infection has taken hold in their body. Such tools, like a new kind of blood test, are now in development and could help to eliminate the “just in case” prescribing of antibiotics.

In the meantime, we are faced with the legacy of these drugs — the possibility that they have affected our size and shape, and made us different people.

Legislated to Health? If People Don’t Take Their Health Into Their Own Hands, Governments May Use Policies to Do It for Them (Science Daily)

ScienceDaily (Aug. 31, 2012) — Obesity rates in North America are a growing concern for legislators. Expanded waistlines mean rising health-care costs for maladies such as diabetes, heart disease and some cancers. One University of Alberta researcher says that if people do not take measures to get healthy, they may find that governments will throw their weight into administrative measures designed to help us trim the fat.

Nola Ries of the Faculty of Law’s Health Law and Science Policy Group has recently published several articles exploring potential policy measures that could be used to promote healthier behaviour. From the possibility of zoning restrictions on new fast-food outlet locations, mandatory menu labels, placing levies on items such as chips and pop or offering cash incentives for leading a more healthy and active lifestyle, she says governments at all levels are looking to adopt measures that will help combat both rising health-care costs and declining fitness levels. But she cautions that finding a solution to such a widespread, complex problem will require a multi-layered approach.

“Since eating and physical activity behaviour are complex and influenced by many factors, a single policy measure on its own is not going to be the magic bullet,” said Ries. “Measures at multiple levels — directed at the food and beverage industry, at individuals, at those who educate and those who restrict — must work together to be effective.”

Junk-food tax: A lighter wallet equals a lighter you?

Ries notes that several countries have already adopted tax measures against snack foods and beverages, similar to “sin taxes” placed on alcohol and tobacco. Although Canada has imposed its GST on various sugary and starchy snacks (no tax is charged on basic groceries such as meats, vegetables and fruits), Ries points to other countries such as France and Romania, where the tax rate is much higher. She says taxing products such as sugar-sweetened beverages would likely not only reduce consumption (and curb some weight gain) if the tax is high enough, but also provide a revenue stream to combat the problem on other levels.

“Price increases through taxation do help discourage consumption of ‘sin’ products, especially for younger and lower-income consumers,” said Ries. “Such taxes would provide a source of government revenue that could be directed to other programs to promote healthier lifestyles.”

Warning: This menu label may make you eat healthier

Ries notes that prevailing thought says putting nutrition-value information where consumers can see it will enable them to make better food choices. She says many locales in the United States have already implemented mandatory menu labelling. Even though some studies say menu labels do not have a significant impact on consumer behaviour, nutrition details might help some people make more informed eating choices.

“Providing information is less coercive than taxation and outright bans, so governments should provide information along with any other more restrictive measure,” said Ries. “If a more coercive policy is being implemented, it’s important for citizens to understand the rationale for it.”

Coaxing our way to good health?

Ries notes that some programs designed to create more active citizens, such as the child fitness tax credit, do not seem to have the desired effect. Yet, she says that offering incentives for living healthier and exercising more may have a greater impact on getting people active. She points to similar programs used for weight loss and smoking cessation, which had a positive effect on behaviour change, at least in the short term. More work needs to be done to establish an enticement plan with longer-term effects, one that may incorporate points accumulated for healthy types of behaviour that could be redeemed for health- and fitness-related products and services. She says investing money into more direct incentive programs may be more effective than messages that simply give general advice about healthy lifestyles.

“Instead of spending more money on educational initiatives to tell people what they already know — like eat your greens and get some exercise — I suggest it’s better to focus on targeted programs that help people make and sustain behaviour change,” said Ries. “Financial incentive programs are one option; the question there is how best to target such programs and to design them to support long-term healthy behaviour.”