Arquivo da tag: Microorganismos

How altered gut microbes cause obesity (Science Daily)

June 8, 2016
Yale University
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

Parceiros inseparáveis (Revista Fapesp)



Associação simbiótica entre protozoário e bactéria ajuda a entender a origem dos eucariotos – organismos com material genético compartimentalizado no núcleo da célula. Os parasitologistas Cristina Motta e Sergio Schenkman explicam essa relação.

Wild sheep show benefits of putting up with parasites (Science Daily)

Date: August 7, 2014

Source: Princeton University

Summary: In the first evidence that natural selection favors an individual’s infection tolerance, researchers have found that an animal’s ability to endure an internal parasite strongly influences its reproductive success. The finding could provide the groundwork for boosting the resilience of humans and livestock to infection.

The researchers examined the relationship between each sheep’s body weight and its level of infection by nematodes, tiny parasitic worms that thrive in the gastrointestinal tract of sheep. This scanning electron micrograph shows nematodes on the surface of a sheep’s gut with a field of view of approximately one centimeter. An economic detriment to sheep farmers, nematodes infect both wild and domesticated sheep, resulting in weight loss, reduced wool growth and death. Credit: Photo by David Smith/Moredun Research Institute

In the first evidence that natural selection favors an individual’s infection tolerance, researchers from Princeton University and the University of Edinburgh have found that an animal’s ability to endure an internal parasite strongly influences its reproductive success. Reported in the journalPLoS Biology, the finding could provide the groundwork for boosting the resilience of humans and livestock to infection.

The researchers used 25 years of data on a population of wild sheep living on an island in northwest Scotland to assess the evolutionary importance of infection tolerance. They first examined the relationship between each sheep’s body weight and its level of infection with nematodes, tiny parasitic worms that thrive in the gastrointestinal tract of sheep. The level of infection was determined by the number of nematode eggs per gram of the animal’s feces.

While all of the animals lost weight as a result of nematode infection, the degree of weight loss varied widely: an adult female sheep with the maximum egg count of 2,000 eggs per gram of feces might lose as little as 2 percent or as much as 20 percent of her body weight. The researchers then tracked the number of offspring produced by each of nearly 2,500 sheep and found that sheep with the highest tolerance to nematode infection produced the most offspring, while sheep with lower parasite tolerance left fewer descendants.

To measure individual differences in parasite tolerance, the researchers used statistical methods that could be extended to studies of disease epidemiology in humans, said senior author Andrea Graham, an assistant professor of ecology and evolutionary biology at Princeton. Medical researchers have long understood that people with similar levels of parasite infection can experience very different symptoms. But biologists are just beginning to appreciate the evolutionary importance of this individual variation.

“For a long time, people assumed that if you knew an individual’s parasite burden, you could perfectly predict its health and survival prospects,” Graham said. “More recently, evolutionary biologists have come to realize that’s not the case, and so have developed statistical tools to measure variation among hosts in the fitness consequences of infection.”

Graham and her colleagues used the wealth of information collected over many years on the Soay sheep living on the island of Hirta, about 100 miles west of the Scottish mainland. These sheep provide a unique opportunity to study the effects of parasites, weather, vegetation changes and other factors on a population of wild animals. Brought to the island by people about 4,000 years ago, the sheep have run wild since the last permanent human inhabitants left Hirta in 1930. By keeping a detailed pedigree, the researchers of the St Kilda Soay Sheep Project can trace any individual’s ancestry back to the beginning of the project in 1985, and, conversely, can count the number of descendants left by each individual.

Expending energy to fight infection

Nematodes puncture an animal’s gut and can impede the absorption of nutrients. Therefore, tolerance to nematode infection could result from an ability to make up for the lost nutrition, or from the ability to repair damage the parasites cause to the gut, Graham said. “This island is way out in the North Atlantic, where the sun doesn’t shine much,” she said. “So tolerant individuals might be the ones who are better able to compete for food or better able to assimilate protein and other useful nutrients from the limited forage.”

Tolerant animals might invest energy in gut repair, but would then be expected to incur costs. Graham and her colleagues identified a similar evolutionary tradeoff in a 2010 study that compared immune-response levels and reproductive success in female Soay sheep. They found that animals with strong antibody responses produced fewer offspring each year, but also lived longer. The team has not yet been able to detect costs of parasite tolerance in the sheep, but such costs could help explain variation in tolerance if the most tolerant animals were at a disadvantage under particular conditions.

While the PLoS Biology findings provide strong evidence that natural selection favors infection tolerance, they do raise questions, such as how the tolerance is generated, and why variation might persist from one generation to the next despite the reproductive advantage of tolerance, Graham said. The data in this study did not permit the researchers to detect a genetic component to tolerance. If genetics do play a role, she suspects multiple genes may interact with environmental factors to determine tolerance; ongoing research will help to tease apart these possibilities.

Understanding the genetic underpinnings of nematode tolerance could someday guide efforts to boost tolerance in livestock by identifying and selectively breeding those animals that exhibit a heightened parasite tolerance, said David Schneider, an associate professor of microbiology and immunology at Stanford University.

“This study shows that parasite tolerance can have a profound effect on animal health and breeding success,” said Schneider, who is familiar with the work but was not involved in it. “In the long term, this suggests that it could be profitable to invest in breeding tolerant livestock.”

In humans and domesticated animals, intestinal parasites are becoming increasingly resistant to the drugs used to treat infections, Graham said. If the availability of nutrients, even just during the first few months of life, impacts lifelong parasite tolerance, simple nutritional supplements could be an effective way to promote tolerance in people. About 2 billion people are persistently infected with intestinal nematode parasites worldwide, mostly in developing nations. Children are especially vulnerable to the worms’ effects, which include anemia, stunted growth and cognitive difficulties.

“Ideally, we would clear the worms from the bellies of the kids who have those heavy burdens,” Graham said. “But if we could also understand how to ameliorate the health consequences and thus promote tolerance of nematodes, that could be a very powerful tool.”

Journal Reference:

  1. Adam D. Hayward, Daniel H. Nussey, Alastair J. Wilson, Camillo Berenos, Jill G. Pilkington, Kathryn A. Watt, Josephine M. Pemberton, Andrea L. Graham. Natural Selection on Individual Variation in Tolerance of Gastrointestinal Nematode Infection. PLoS Biology, 2014; 12 (7): e1001917 DOI:10.1371/journal.pbio.1001917

Diet affects males’ and females’ gut microbes differently (Science Daily)

Date: July 29, 2014

Source: University of Texas at Austin

Summary: The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a new study. These results suggest that therapies designed to improve human health and treat diseases through nutrition might need to be tailored for each sex.

Illustration by Marianna Grenadier and Jenna Luecke. Credit: Image courtesy of University of Texas at Austin

The microbes living in the guts of males and females react differently to diet, even when the diets are identical, according to a study by scientists from The University of Texas at Austin and six other institutions published this week in the journal Nature Communications. These results suggest that therapies designed to improve human health and treat diseases through nutrition might need to be tailored for each sex.

The researchers studied the gut microbes in two species of fish and in mice, and also conducted an in-depth analysis of data that other researchers collected on humans. They found that in fish and humans diet affected the microbiota of males and females differently. In some cases, different species of microbes would dominate, while in others, the diversity of bacteria would be higher in one sex than the other.

These results suggest that any therapies designed to improve human health through diet should take into account whether the patient is male or female.

Only in recent years has science begun to completely appreciate the importance of the human microbiome, which consists of all the bacteria that live in and on people’s bodies. There are hundreds or even thousands of species of microbes in the human digestive system alone, each varying in abundance.

Genetics and diet can affect the variety and number of these microbes in the human gut, which can in turn have a profound influence on human health. Obesity, diabetes, and inflammatory bowel disease have all been linked to low diversity of bacteria in the human gut.

One concept for treating such diseases is to manipulate the microbes within a person’s gut through diet. The idea is gaining in popularity because dietary changes would make for a relatively cheap and simple treatment.

Much has to be learned about which species, or combination of microbial species, is best for human health. In order to accomplish this, research has to illuminate how these microbes react to various combinations of diet, genetics and environment. Unfortunately, to date most such studies only examine one factor at a time and do not take into account how these variables interact.

“Our study asks not just how diet influences the microbiome, but it splits the hosts into males and females and asks, do males show the same diet effects as females?” said Daniel Bolnick, professor in The University of Texas at Austin’s College of Natural Sciences and lead author of the study.

While Bolnick’s results identify that there is a significant difference in the gut microbiota for males and females, the dietary data used in the analysis are organized in complex clusters of disparate factors and do not easily translate into specific diet tips, such as eating more vegetables or less meat.

“To guide people’s behavior, we need to know what microbes are desirable for people,” said Bolnick. “Diet and sex do interact to influence the microbes, but we don’t yet know what a desirable target for microbes is. Now we can go in with eyes open when we work on therapies for gut microbe problems, as many involve dietary changes. We can walk into those studies looking for something we weren’t aware of before. All along we treated diet as if it works the same for men and women. Now we’ll be approaching studies of therapies in a different way.”

Why men and women would react differently to changes in diet is unclear, but there are a couple of possibilities. The hormones associated with each sex could potentially influence gut microbes, favoring one strain over another. Also, the sexes often differ in how their immune systems function, which could affect which microbes live and die in the microbiome.

One notable exception in Bolnick’s results was in the mice. Although there was a tiny difference between male and female mice, for the most part the microbiota of each sex reacted to diet in the same manner. Because most dietary studies are conducted on mice, this result could have a huge effect on such research, and it raises questions about how well studies of gut microbes in lab mice can be generalized to other species, particularly humans.

“This means that most of the research that’s being done on lab mice — we need to treat that with kid gloves,” said Bolnick.

Bolnick’s co-authors are Lisa Snowberg (UT Austin); Philipp Hirsch (University of Basel and Uppsala University); Christian Lauber and Rob Knight (University of Colorado, Boulder); Elin Org, Brian Parks and Aldons Lusis (University of California, Los Angeles); J. Gregory Caporaso (Northern Arizona University and Argonne National Laboratory); and Richard Svanbäck (Uppsala University).

This research was funded by the Howard Hughes Medical Institute, the David and Lucile Packard Foundation and the Swedish Research Council.

Journal Reference:

  1. Daniel I. Bolnick, Lisa K. Snowberg, Philipp E. Hirsch, Christian L. Lauber, Elin Org, Brian Parks, Aldons J. Lusis, Rob Knight, J. Gregory Caporaso, Richard Svanbäck. Individual diet has sex-dependent effects on vertebrate gut microbiota. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5500

Biologists Unlock ‘Black Box’ to Underground World: How Tiny Microbes Make Life Easier for Humans (Science Direct)

Jan. 2, 2013 — A BYU biologist is part of a team of researchers that has unlocked the “black box” to the underground world home to billions of microscopic creatures.

That first peek inside, recently published in the Proceedings of the National Academy of Sciences, may well explain how the number of species in an ecosystem changes the way it functions.

“The organisms that live in soil do all kinds of important things for us — they decompose and decontaminate our waste and toxic chemicals, purify our water, prevent erosion, renew fertility,” said BYU biology professor Byron Adams, a study coauthor. “But we know very little about how they do this. What species need to be present? What are the different jobs that we need them to do?”

For their analysis, Adams and his colleagues took 16 soil samples from all reaches of the globe, from Antarctica to tropical forest locations, extracted the DNA out of all the organisms in each sample, and sequenced it.

With information about the genome (the complete set of its DNA and all of its genes) of each microbe in the soil, the researchers were able to see which organisms do what, and whether or not their functional roles are redundant or unique.

“People think you’re going to pick up a handful of dirt anywhere in the world and you’ll pretty much have the same bunch of microbes doing pretty much the same things,” Adams said. “That’s simply not true. They function very differently based on their environment. And when you have more species, you get more, and different functions.”

Having several different species that do the same job might mean that if one species goes extinct then the others can pick up the slack. On the other hand, in ecosystems like deserts, where there are few species and even fewer jobs, removing some species could result in collapse, or failure of the ecosystem to provide the services we need.

Understanding the relationship between biodiversity and the different jobs that soil microbes do is a first step towards understanding how to better harness these organisms in order to prevent the collapse of the very systems that provide critical ecosystem services, such as fertile soil and clean water.

“The most obvious applications of this understanding will probably be in agricultural ecosystems,” Adams said.

A better understanding of below-ground ecosystems can help humans predict how those systems will respond to things such as climate change or perturbations to the soil from mining, drilling or waste. And, hopefully, that understanding can help prevent agricultural or environmental catastrophes.

“We’ve been walking around on soil since the beginning of time and never really knew what was going on underneath us,” Adams said. “Now we will be able to make predictions of how ecosystems function, what causes them to collapse, and perhaps even predict, where collapses will take place and how we can prevent them.”

The lead author on the study was Noah Fierer, an associate professor of Ecology and Evolutionary Biology at the University of Colorado, Boulder.

The researchers’ data also may have something to say about how new species form. For centuries it was thought that geographic barriers (like mountains, peninsulas, rivers and deserts) were the primary engines of speciation. However, it could be that interactions with other species are just as important.

The authors believe this study will open up significant additional research addressing speciation and the evolution of microbial communities.

Journal Reference:

  1. N. Fierer, J. W. Leff, B. J. Adams, U. N. Nielsen, S. T. Bates, C. L. Lauber, S. Owens, J. A. Gilbert, D. H. Wall, J. G. Caporaso. Cross-biome metagenomic analyses of soil microbial communities and their functional attributesProceedings of the National Academy of Sciences, 2012; 109 (52): 21390 DOI:10.1073/pnas.1215210110