Antibiotics that Kill Gut Bacteria also Stop Growth of Brain Cells

Antibiotics strong enough to kill off gut bacteria can also stop the growth of new brains cells in the hippocampus, a section of the brain associated with with memory, reports a study in mice published in Cell Reports on May 19. Researchers also uncovered a clue to why - a type of white blood cell seems to act as a communicator between the brain, the immune system and the gut.

Wolf first saw clues that the immune system could influence the health and growth of brain cells through research into T cells nearly 10 years ago. But there were few studies that found a link from the brain to the immune system and back to the gut.

In the study, the researchers gave a group of mice enough antibiotics for them to become nearly free of intestinal microbes, Compared to untreated mice, the mice who lost their healthy gut bacteria performed worse in memory tests and showed a loss of neurogenesis (new brain cells) in a section of their  hippocampus that typically produces new brain cells throughout an individual's lifetime. At the same time that the mice experienced memory and neurogenesis loss, the research team detected a lower level of white blood cells (specifically monocytes), marked with Ly6Chi in the brain, blood and bone marrow. So researchers tested whether it was indeed the Ly6Chi monocytes behind the changes in neurogenesis and memory. 

In another experiment, the team compared untreated mice to mice that had healthy gut bacteria levels but low levels of Ly6Chi either due to genetics or due to treatment with antibodies that target Ly6Chi cells. In both cases, mice with low Ly6Chi levels in mice treated with antibiotics, then memory and neurogenesis deficits as mice in the other experiment who had lost gut bacteria.Furthermore, if the researchers replaced the Ly6Chi levels in mice treated with antibiotics, them memory and neurogenesis improved.
Luckily, the adverse side effects of the antibiotics could be reversed. Mice who received probiotics or who exercised on a wheel after receiving antibiotics regained memory and neurogenesis.
Luckily, the adverse side effects of the antibiotics could be reversed. Mice who received probiotics or who exercised on a wheel after receiving antibiotics regained memory and neurogenesis.
But one result in the experiment raised more questions about the gut's bacteria and the link between Ly6Chi and the brain. While probiotics helped the mice regain memory, fecal transplants to restore a healthy gut bacteria did not have an effect.
In future, researchers also hope to see more clinical trails investigating whether probiotic treatments will improve symptoms in patients with neurodegenerative and psychiatric disorder.

Bacterial communities of female genital tract have impact on inflammation, HIV risk

The most common bacterial community in the genital tract among healthy South African women not only is significantly different from that of women in developed countries but also leads to elevated levels of inflammatory proteins, which could increase the risk of HIV infection, new research concludes. 

"Ours is the first study to identify a specific bacterial community in the genital tract of healthy women that is highly pro-inflammatory, and we show this community is common in the women we studied in South Africa," says Douglas Kwon, MD, PhD, of the Ragon Institute and the MGH division of Infectious Diseases, senior author of the report. "We also identified specific mechanisms by which the immune system senses these bacterial species and potential mechanisms linking that response to increased HIV susceptibility."
The authors note that, although inflammatory reactions in the female genital tract can prevent or eliminate many sexually transmitted infections, activation of the immune system paradoxically increases the risk that exposure to HIV will lead to infection. In the past, the bacterial population of the female tract was believed to be very simple and -- based on what was seen in white, premenopausal women -- dominated by a single Lactobacillus species. Since mild vaginal infections that alter the dominant microbial community can increase the risk of acquiring HIV and other sexually transmitted diseases, the researchers designed the current study to investigate whether differences in the genital microbial communities of healthy women might affect overall susceptibility to infection.
Analysis of genital samples from a group of 94 young black South African women -- who were HIV negative and had no disease symptoms -- revealed that only a minority had the sort of Lactobacillus-dominant bacterial communities commonly seen in U.S. women. The researchers grouped the samples they studied into four community types -- what they called cervicotypes -- based on the dominant bacterial species. The most common cervicotype among the study participants was very diverse, with low levels of Lactobacillus and no single dominant bacterial group.
To assess levels of immune activation in the study participants, the researchers measured levels of the immune system signaling molecules called cytokines in vaginal fluid samples and found significant individual differences -- as much as 1,000-fold in some cases. Elevated cytokines were not associated with active sexually transmitted infections or with factors such as sexual frequency or the use of condoms or hormonal contraceptives. Comparing cytokine levels among the cervicotypes revealed that the low-Lactobacillus, high-diversity communities were more than four times as likely to have elevated genital inflammatory cytokines. In fact, the presence of community was a better predictor of inflammation than was the presence of sexually transmitted diseases or other vaginal infections.
The researchers found that women with the highest levels of genital inflammation also had elevated levels of CCR5+ CD4+ T cells, the cells that are infected by HIV, in their genital tracts. "It has been shown that having a higher frequency of these HIV target cells at the site of exposure increases the risk of infection," says study lead author Melis Anahtar, an MD/PhD candidate in the Harvard/MIT Division of Health Sciences and Technology. "It's possible that treatments targeting specific genital bacteria could improve the effectiveness of measures -- such as antiretroviral vaginal gels -- designed to prevent HIV infection. In addition, finding that women with elevated genital inflammation may be three times more likely to become HIV-infected suggests that generally targeting the genital microbial population may further reduce risk."
An assistant professor of Medicine at Harvard Medical School, Kwon adds, "Understanding the impact of differences in the genital microbial population could also have implications for pregnant women and their infants. Some of the pro-inflammatory species that we found in our study were originally found in infected amniotic fluid and may contribute to the risk for premature birth and other complications of pregnancy." The research team is now investigating the specific mechanisms by which the immune system senses the presence of specific bacterial species in the female genital tract as well as examining the potential role of the broader microbial population, including viruses and fungi.

This story is taken from Science Daily

How bacteria survive antibiotics may improve treatment of infectious diseases

Infectious diseases kill more people worldwide than any other single cause, but treatment often fails because a small fraction of bacterial cells can transiently survive antibiotics and recolonize the body. A study reveals that these so-called persisters form in response to adverse conditions through the action of a molecule called Obg, which plays an important role in all major cellular processes in multiple bacterial species. 

"Persisters pose a fundamental hurdle to the treatment of chronic and biofilm infections by bacterial and fungal pathogens," says co-senior study author Jan Michiels of KU Leuven -- University of Leuven. "Our findings suggest that combining antibiotic treatment with a therapy specifically targeting the novel persistence pathway we discovered would prove advantageous by enhancing patient responses to antibiotic treatment and by shortening antibiotic therapy duration."

Persistence is triggered in part by bacterial toxins that shut down critical cellular processes, such as protein synthesis or energy production, forcing the bacterial cells to enter a dormant state in which they are no longer susceptible to killing by antibiotics. But the mechanisms underlying toxin-mediated persistence have not been clear, and little is known about how environmental signals trigger bacterial persistence.

To answer these questions, Michiels and his team focused on the potential role of Obg because this enzyme is at the nexus of major cellular processes, such as protein and DNA synthesis, and it triggers dormancy when cellular energy levels are low. They found that high levels of Obg protected nutrient-starved intestinal bacteria called Escherichia coli and the pathogen Pseudomonas aeruginosa from two antibiotics that interfere with DNA and protein synthesis. "This indicates that a common mechanism to produce persisters is active in different bacterial species," Michiels says. "Therefore, Obg could be a target for the development of novel therapeutics against infectious diseases."

Obg induced persistence in E. coli by increasing levels of a toxic molecule called HokB, which causes small holes to form in the bacterial membrane, thereby halting energy production and triggering dormancy. However, deletion of hokB did not decrease persistence in E. coli, and this gene was absent in P. aeruginosa, suggesting that persistence is controlled by at least one other Obg-regulated pathway waiting to be discovered. Another question for future research is how persistent cells can recover from toxin-induced damage and switch back to the normal, non-persistent state. "Answering these fundamental questions will pave the way for translational research that could ultimately lead to better therapies to combat bacterial infections."

This story is taken from Science Daily

Enormous array of bacteria discovered on common bird; could have agricultural implications

A microbiology professor and an ornithology professor have discovered that one of North America's most common migratory birds – the Dark-eyed Junco – carries on its feathers a remarkable diversity of plant bacteria, the greatest ever found on wild birds. And while many of these bacteria may be harmful to plants, the bacteria could also be of great benefit. 

And while many of these bacteria may be harmful to plants, the bacteria could also be of great benefit.
That's what Schneegurt and Rogers, researchers from two different disciplines with one common goal, are working to determine.
"Some of the bacteria we find are beneficial to plants. Some are harmful to plants," Schneegurt says. "How does that balance work out for the plants? That's not clear."
But what is clear is the importance of this research.
Wild birds interact with the environment, contacting soils and plants with their feathers. Those feathers filter the air, gathering particles of soil and plant matter. Because microbes are everywhere in nature, feathers naturally carry a diverse community of microbes. And as for Juncos specifically, these migratory birds can fly 200 or more miles a night, making them highly capable of spreading bacteria over large swaths of land.
Pathogens are notoriously costly for agriculture, so the benefits of preventing possible diseases or, conversely, identifying helpful bacteria, are vital.
"The Juncos are probably good guys in all of this," Rogers says. "It may be that they're spreading pathogens, but theoretically it's possible that they're also beneficial instead of just being negative."
Possible commercial applications
Much of Schneegurt and Rogers' research work was conducted at the WSU Biological Field Station, Ninnescah Reserve. They hope to secure further funding for their project.
Their next step is to test the isolates they've captured on plants such as tomatoes, potatoes, wheat, oat and rye to see if they have qualities of beneficial bacteria or those of pathogens.
A potential benefit may be bacteria that produce growth-encouraging hormones. Another possibility would be bacteria that actually inhibit fungi which are trying to damage the plant.
The pair have also found many isolates that actually degrade bird feathers. Not good for the birds, but of possible interest to biotechnology companies. Schneegurt says these bacteria could be used to break down enzymes in laundry detergent, as well as other industrial and potential medical uses.
"This is where the basic description of natural phenomenon -- in this case communities on bird feathers -- can lead to commercial applications," he says.
An innovative approach
Rogers and Schneegurt weren't planning on conducting a study of this scale on Junco bacteria. Last year they were reviewing WSU grad student John "Wes" Dille's thesis, which described the microbial community on Junco feathers.
"We weren't looking for this," Schneegurt says. "We were originally looking to simply describe the community of bacteria found on the bird feathers. It's serendipity."
He and Rogers thought previous work of the scientific community on feather bacteria wasn't as complete as it could be.
"I said, 'I think we could do a better job,' and as it turns out, we did," Schneegurt says.
Why is that? In large part, they say, because of their ability to put their unique skills and knowledge together for this study.
"Here we have a professional long-term ornithologist and a professional long-term microbiologist putting our major backgrounds together to make a major discovery," Rogers says.
Schneegurt says hearing someone else's perspective will inevitably result in better work.
"If you listen to the same guys all the time, you only know what they know," he says. "Iinteractions lead to things you would never imagine happening. That's where real innovation comes from."

This story is taken from Science Daily