Posts Tagged ‘center’

Do gut bacteria rule our minds? In an ecosystem within us, microbes evolved to sway food choices

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.

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.

“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.

source : http://www.sciencedaily.com/releases/2014/08/140815192240.htm

Injected bacteria shrink tumors in rats, dogs and humans

In its natural form, C. novyi is found in the soil and, in certain cases, can cause tissue-damaging infection in cattle, sheep and humans. The microbe thrives only in oxygen-poor environments, which makes it a targeted means of destroying oxygen-starved cells in tumors that are difficult to treat with chemotherapy and radiation. The Johns Hopkins team removed one of the bacteria’s toxin-producing genes to make it safer for therapeutic use.

For the study, the researchers tested direct-tumor injection of the C. novyi-NT spores in 16 pet dogs that were being treated for naturally occurring tumors. Six of the dogs had an anti-tumor response 21 days after their first treatment. Three of the six showed complete eradication of their tumors, and the length of the longest diameter of the tumor shrunk by at least 30 percent in the three other dogs.

Most of the dogs experienced side effects typical of a bacterial infection, such as fever and tumor abscesses and inflammation, according to a report on the work published online Aug. 13 in Science Translational Medicine.

In a Phase I clinical trial of C. novyi-NT spores conducted at MD Anderson Cancer Center, a patient with an advanced soft tissue tumor in the abdomen received the spore injection directly into a metastatic tumor in her arm. The treatment significantly reduced the tumor in and around the bone. “She had a very vigorous inflammatory response and abscess formation,” according to Nicholas Roberts, Vet.M.B., Ph.D. “But at the moment, we haven’t treated enough people to be sure if the spectrum of responses that we see in dogs will truly recapitulate what we see in people.”

“One advantage of using bacteria to treat cancer is that you can modify these bacteria relatively easily, to equip them with other therapeutic agents, or make them less toxic as we have done here, ” said Shibin Zhou, M.D., Ph.D., associate professor of oncology at the Cancer Center. Zhou is also the director of experimental therapeutics at the Kimmel Cancer Center’s Ludwig Center for Cancer Genetics and Therapeutics. He and colleagues at Johns Hopkins began exploring C. novyi’s cancer-fighting potential more than a decade ago after studying hundred-year old accounts of an early immunotherapy called Coley toxins, which grew out of the observation that some cancer patients who contracted serious bacterial infections showed cancer remission.

The researchers focused on soft tissue tumors because “these tumors are often locally advanced, and they have spread into normal tissue,” said Roberts, a Ludwig Center and Department of Pathology researcher. The bacteria cannot germinate in normal tissues and will only attack the oxygen-starved or hypoxic cells in the tumor and spare healthy tissue around the cancer.

Verena Staedtke, M.D., Ph.D., a Johns Hopkins neuro-oncology fellow, first tested the spore injection in rats with implanted brain tumors called gliomas. Microscopic evaluation of the tumors showed that the treatment killed tumor cells but spared healthy cells just a few micrometers away. The treatment also prolonged the rats’ survival, with treated rats surviving an average of 33 days after the tumor was implanted, compared with an average of 18 days in rats that did not receive the C. noyvi-NT spore injection.

The researchers then extended their tests of the injection to dogs. “One of the reasons that we treated dogs with C. novyi-NT before people is because dogs can be a good guide to what may happen in people,” Roberts said. The dog tumors share many genetic similarities with human tumors, he explained, and their tumors appeared spontaneously as they would in humans. Dogs are also treated with many of the same cancer drugs as humans and respond similarly.

The dogs showed a variety of anti-tumor responses and inflammatory side effects.

Zhou said that study of the C. novyi-NT spore injection in humans is ongoing, but the final results of their treatment are not yet available. “We expect that some patients will have a stronger response than others, but that’s true of other therapies as well. Now, we want to know how well the patients can tolerate this kind of therapy.”

It may be possible to combine traditional treatments like chemotherapy with the C. novyi-NT therapy, said Zhou, who added that the researchers have already studied these combinations in mice.

“Some of these traditional therapies are able to increase the hypoxic region in a tumor and would make the bacterial infection more potent and increase its anti-tumor efficiency,” Staedtke suggested. “C. novyi-NT is an agent that could be combined with a multitude of chemotherapy agents or radiation.”

“Another good thing about using bacteria as a therapeutic agent is that once they’re infecting the tumor, they can induce a strong immune response against tumor cells themselves,” Zhou said.

Previous studies in mice, he noted, suggest that C. novyi-NT may help create a lingering immune response that fights metastatic tumors long after the initial bacterial treatment, but this effect remains to be seen in the dog and human studies.

source : http://www.sciencedaily.com/releases/2014/08/140813173906.htm

Protein found to block benefits of vitamin A cancer therapy

Details of the study were published this week in the online edition of the journal Cancer Research, a journal of the American Association for Cancer Research. The team of scientists led by Devanand Sarkar, M.B.B.S., Ph.D., demonstrated that the protein AEG-1 binds to retinoid X receptors (RXR), which help regulate cell growth and development. RXR is typically activated by retinoic acid, but the overexpressed AEG-1 proteins found in cancer cells block these signals and help promote tumor growth. Using complex animal models, the researchers showed that blocking the production of AEG-1 allowed retinoic acid to profoundly kill liver cancer cells.

“Our findings are the first to show that AEG-1 interacts with the retinoid X receptor,” says Sarkar, Harrison Scholar at VCU Massey Cancer Center, Blick Scholar and associate professor in the Department of Human and Molecular Genetics and member of the VCU Institute of Molecular Medicine (VIMM) at VCU School of Medicine. “This research has immediate clinical relevance such that physicians could begin screening cancer patients for AEG-1 expression levels in order to determine whether retinoic acid should be prescribed.”

Sarkar and his colleagues have been studying AEG-1 for years. They were the first to create a mouse model demonstrating the role of AEG-1 in liver cancer, and they have been actively working to develop targeted therapies that block AEG-1 production. The present study expanded their knowledge of the molecular interactions of AEG-1.

“We are continuing to test combination therapies involving AEG-1 inhibition and retinoic acid in animal models, and the initial results are promising,” says Sarkar. “If we continue to see these results in more complex experiments, we hope to eventually propose a phase 1 clinical trial in patients with liver cancer.”

Sarkar collaborated on this study with Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and co-leader of the Cancer Molecular Genetics research program at Massey, chairman of the Department of Human and Molecular Genetics at VCU School of Medicine and director of the VIMM; Jolene Windle, Ph.D., professor in the Department of Human and Molecular Genetics at the VCU School of Medicine and Irene Shaw Grigg Distinguished Professor in Genetics Research, co-leader of the Cancer Molecular Genetics research program and resource director of the Transgenic/Knock-out Mouse Facility at Massey; Luni Emdad, M.B.B.S., Ph.D., member of the Cancer Molecular Genetics research program at Massey and assistant professor in the Department of Human and Molecular Genetics at the VCU School of Medicine; Jyoti Srivastava, Ph.D., Chadia L. Robertson, Devaraja Rajasekaran, Ph.D., Rachel Gredler and Ayesha Siddiq, Ph.D., all from the Department of Human and Molecular Genetics at the VCU School of Medicine; Shobha Ghosh, Ph.D., associate chair for research in the Department of Internal Medicine at the VCU School of Medicine; Phillip B. Hylemon, Ph.D., member of the Cancer Cell Signaling research program at Massey and professor of microbiology and immunology at the VCU School of Medicine; Gregorio Gil, Ph.D., professor of biochemistry and molecular biology at the VCU School of Medicine; and Khalid Shah, Ph.D., and Deepak Bhere, Ph.D., from Harvard Medical School.

This study was supported by National Cancer Institute grant R01 CA 138540; National Institutes of Health grant R01 CA134721; the James S. McDonnel Foundation; and, in part, by VCU Massey Cancer Center’s NIH-NCI Cancer Center Support Grant P30 CA016059.

source : http://www.sciencedaily.com/releases/2014/08/140814003825.htm