It sounds like science fiction, but it seems that bacteria within us – which outnumber our own cells about 100-fold – may very well be affecting both our cravings and moods to get us to eat what they want, and often are driving us toward obesity.
In an article published this week in the journal BioEssays, researchers from UC San Francisco, Arizona State University and University of New Mexico concluded from a review of the recent scientific literature that microbes influence human eating behavior and dietary choices to favor consumption of the particular nutrients they grow best on, rather than simply passively living off whatever nutrients we choose to send their way.
Bacterial species vary in the nutrients they need. Some prefer fat, and others sugar, for instance. But they not only vie with each other for food and to retain a niche within their ecosystem – our digestive tracts – they also often have different aims than we do when it comes to our own actions, according to senior author Athena Aktipis, PhD, co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF.
Are we at the mercy of our gut bacteria? The above image illustrates how microbes can "pull our strings," driving us to crave foods that give them the nutrients they need, including fat and sugar.
While it is unclear exactly how this occurs, the authors believe this diverse community of microbes, collectively known as the gut microbiome, may influence our decisions by releasing signaling molecules into our gut. Because the gut is linked to the immune system, the endocrine system and the nervous system, those signals could influence our physiologic and behavioral responses.
“Bacteria within the gut are manipulative,” said Carlo Maley, PhD, director of the UCSF Center for Evolution and Cancer and corresponding author on the paper. “There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not.”
Fortunately, it’s a two-way street. We can influence the compatibility of these microscopic, single-celled houseguests by deliberating altering what we ingest, Maley said, with measurable changes in the microbiome within 24 hours of diet change.
“Our diets have a huge impact on microbial populations in the gut,” Maley said. “It’s a whole ecosystem, and it’s evolving on the time scale of minutes.”
There are even specialized bacteria that digest seaweed, found in humans in Japan, where seaweed is popular in the diet.
Research suggests that gut bacteria may be affecting our eating decisions in part by acting through the vagus nerve, which connects 100 million nerve cells from the digestive tract to the base of the brain.
Athena Aktipis, PhD
Carlo Maley, PhD
“Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good,” said Aktipis, who is currently in the Arizona State University Department of Psychology.
In mice, certain strains of bacteria increase anxious behavior. In humans, one clinical trial found that drinking a probiotic containing Lactobacillus casei improved mood in those who were feeling the lowest.
Maley, Aktipis and first author Joe Alcock, MD, from the Department of Emergency Medicine at the University of New Mexico, proposed further research to test the sway microbes hold over us. For example, would transplantation into the gut of the bacteria requiring a nutrient from seaweed lead the human host to eat more seaweed?
The speed with which the microbiome can change may be encouraging to those who seek to improve health by altering microbial populations. This may be accomplished through food and supplement choices, by ingesting specific bacterial species in the form of probiotics, or by killing targeted species with antibiotics. Optimizing the balance of power among bacterial species in our gut might allow us to lead less obese and healthier lives, according to the authors.
“Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating,” the authors wrote.
The authors met and first discussed the ideas in the BioEssays paper at a summer school conference on evolutionary medicine two years ago.
Aktipis, who is an evolutionary biologist and a psychologist, was drawn to the opportunity to investigate the complex interaction of the different fitness interests of microbes and their hosts and how those play out in our daily lives. Maley, a computer scientist and evolutionary biologist, had established a career studying how tumor cells arise from normal cells and evolve over time through natural selection within the body as cancer progresses.
In fact, the evolution of tumors and of bacterial communities are linked, points out Aktipis, who said some of the bacteria that normally live within us cause stomach cancer and perhaps other cancers.
“Targeting the microbiome could open up possibilities for preventing a variety of disease from obesity and diabetes to cancers of the gastro-intestinal tract. We are only beginning to scratch the surface of the importance of the microbiome for human health,” she said.
The co-authors’ BioEssays study was funded by the National Institutes of Health, the American Cancer Society, the Bonnie D. Addario Lung Cancer Foundation and the Institute for Advanced Study, in Berlin.
UC San Francisco (UCSF), now celebrating the 150th anniversary of its founding, is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic, biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco.
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CORAL GABLES, Fla. (June 25, 2014) — With the continuing need for very small devices in therapeutic applications, there is a growing demand for the development of nanoparticles that can transport and deliver drugs to target cells in the human body.
Recently, researchers created nanoparticles that under the right conditions, self-assemble – trapping complementary guest molecules within their structure. Like tiny submarines, these versatile nanocarriers can navigate in the watery environment surrounding cells and transport their guest molecules through the membrane of living cells to sequentially deliver their cargo.
Although the transport of molecules inside cells with nanoparticles has been previously achieved using various methods, researchers have developed nanoparticles capable of delivering and exchanging complementary molecules. For practical applications, these nanocarriers are highly desirable, explains Francisco Raymo, professor of chemistry in the University of Miami College of Arts and Sciences and lead investigator of this project.
"The ability to deliver distinct species inside cells independently and force them to interact, exclusively in the intracellular environment, can evolve into a valuable strategy to activate drugs inside cells," Raymo says.
The new nanocarriers are15 nanometers in diameter. They are supramolecular constructs made up of building blocks called amphiphilic polymers. These nanocarriers hold the guest molecules within the confines of their water-insoluble interior and use their water-soluble exterior to travel through an aqueous environment. As a result, these nanovehicles are ideal for transferring molecules that would otherwise be insoluble in water, across a liquid environment.
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"Once inside a living cell, the particles mix and exchange their cargo. This interaction enables the energy transfer between the internalized molecules," says Raymo, director of the UM laboratory for molecular photonics. "If the complementary energy donors and acceptors are loaded separately and sequentially, the transfer of energy between them occurs exclusively within the intracellular space," he says. "As the energy transfer takes place, the acceptors emit a fluorescent signal that can be observed with a microscope."
Essential to this mechanism are the noncovalent bonds that loosely hold the supramolecular constructs together. These weak bonds exist between molecules with complementary shapes and electronic properties. They are responsible for the ability of the supramolecules to assemble spontaneously in liquid environments. Under the right conditions, the reversibility of these weak noncovalent contacts allows the supramolecular constructs to exchange their components as well as their cargo.
The experiments were conducted with cell cultures. It is not yet known if the nanoparticles can actually travel through the bloodstream.
"That would be the dream, but we have no evidence that they can actually do so," Raymo says. "However, this is the direction we are heading."
The next phase of this investigation involves demonstrating that this method can be used to do chemical reactions inside cells, instead of energy transfers.
"The size of these nanoparticles, their dynamic character and the fact that the reactions take place under normal biological conditions (at ambient temperature and neutral environment) makes these nanoparticles an ideal vehicle for the controlled activation of therapeutics, directly inside the cells," Raymo says.
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The current study is titled "Intracellular guest exchange between dynamic supramolecular hosts." It's published in the Journal of the American Chemical Society. Other authors are John F. Callan, co-corresponding author of the study, from the School of Pharmacy and Pharmaceutical Sciences at the University of Ulster; Subramani Swaminathan and Janet Cusido from the UM's Laboratory for Molecular Photonics, Department of Chemistry in the College of Arts and Sciences; and Colin Fowley and Bridgeen McCuaghan, School of Pharmacy and Pharmaceutical Sciences at the University of Ulster.
The University of Miami's mission is to educate and nurture students, to create knowledge, and to provide service to our community and beyond. Committed to excellence and proud of our diversity of our University family, we strive to develop future leaders of our nation and the world.
A photo of the fungus Aspergillus versicolor. Credit: McMaster University
A fungus living in the soils of Nova Scotia could offer new hope in the pressing battle against drug-resistant germs that kill tens of thousands of people every year, including one considered a serious global threat.
A team of researchers led by McMaster University has discovered a fungus-derived molecule, known as AMA (Aspergillomarasmine A), which is able to disarm one of the most dangerous antibiotic-resistance genes: NDM-1 or New Delhi Metallo-beta-Lactamase-1, identified by the World Health Organization as a global public health threat.
"This is public enemy number one," explains Gerry Wright, director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University.
"It came out of nowhere, it has spread everywhere and has basically killed our last resource of antibiotics, the last pill on the shelf, used to treat serious infections," he says.
Discovering the properties of the fungus-derived molecule is critical because it can provide a means to target and rapidly block the drug-resistant pathogens that render carbapenem antibiotics—a class of drugs similar to penicillin—ineffective.
"Simply put, the molecule knocks out NDM-1 so the antibiotics can do their job," says Wright.
Seeking an answer to the riddle of resistance in the natural environment is a far more promising approach than trying to discover new antibiotics, a challenge which has perplexed scientists for decades. No new classes of antibiotics have been discovered since the late 1980s, leaving physicians with very few tools to fight life-threatening infections.
"Not only do we have the emergence of an antibiotic resistance gene that is targeting the last drug resource we have left, but it is carried by organisms that cause all sorts of challenging diseases and are multi-drug-resistant already. It has been found not only in clinics but in the environment—in contaminated water in South Asia—which has contributed to its spread over the globe," explains Wright. "Our thinking was that if we could find a molecule that blocks NDM-1 then these antibiotics would be useful again."
Wright and his team from McMaster, University of British Columbia and Cardiff University in Wales created a sophisticated screening method to take the NDM-1 gene, combine it with harmless E. coli bacteria and then isolate a molecule capable of stopping NDM-1 in its tracks.
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