A new study of the human microbiome has uncovered millions of previously unknown genes from microbial communities in the human gut, skin, mouth, and vaginal microbiome, allowing for new insights into the role these microbes play in human health and disease.
Scientists have tapped into the microbiome of elite runners and rowers, and have identified particular bacteria that may aid athletic performance. The goal is to develop probiotic supplements that may help athletes — and even amateur fitness enthusiasts — recover from a tough workout or more efficiently convert nutrients to energy. The researchers will present their work today at the 254th National Meeting & Exposition of the American Chemical Society.
Children with lower diversity of microbial species in their intestines are more susceptible to severe infection with the Entamoeba histolytica parasite, according to a new study.
Uncircumcised men with high levels of anaerobic penile bacteria at higher risk for HIV, suggests new research.
Chronic obstructive pulmonary disease (COPD) can result in structural changes within the lungs over time. Scientists have now been able to show that these changes not only affect the organ itself, but also the bacteria that live in the lung.
People with diabetes are susceptible to periodontitis, a gum infection that can result in tooth loss. New research helps explain why: Diabetes triggers changes in the oral microbiome that enhance inflammation and the risk of bone loss
Bugs in your eyes may be a good thing. Resident microbes living on the eye are essential for immune responses that protect the eye from infection, new research shows. The study demonstrates the existence of a resident ocular microbiome that trains the developing immune system to fend off pathogens.
Even in healthy individuals, the skin plays host to a menagerie of bacteria, fungi and viruses. Growing scientific evidence suggests that this lively community, collectively known as the skin microbiome, serves an important role in healing, allergies, inflammatory responses and protection from infection.
In a new study, researchers at the University of Pennsylvania have shown for the first time that, not only can infection with the Leishmania parasite alter the skin microbiome of affected mice, but this altered microbial community can be passed to uninfected mice that share a cage with the infected animals.
Mice with the perturbed microbiome, or dysbiosis, had heightened inflammatory responses and more severe disease when they were subsequently infected with Leishmania. The findings are published in the journal Cell Host & Microbe.
“To my knowledge, this is the first case where anyone has shown that a pre-existing skin microbiome can influence the outcome of an infection or a disease,” said Elizabeth Grice, co-senior author and assistant professor in the departments of Dermatology and Microbiology in Penn’s Perelman School of Medicine. “This opens the door to many other avenues of research.”
In addition, when the researchers examined samples from human Leishmania patients, they found similar patterns of dysbiosis as in the infected mice, a hint that the findings may extend to people.
“The transmission of dysbiosis in the skin from one animal to another is a key finding,” said Phillip Scott, professor of immunology in the Department of Pathobiology in Penn’s School of Veterinary Medicine and co-senior author on the study. “And the fact that we saw similar patterns of dysbiosis in humans suggests there could be some very practical implications of our work when it comes to treating people with leishmaniasis.”
Grice and Scott collaborated with researchers from Penn Medicine and Penn Vet, including lead author Ciara Gimblet, a Ph.D. student in Scott’s lab, and colleagues from Brazil’s Oswaldo Cruz Foundation.
Cutaneous leishmaniasis is a tropical disease caused by a parasite and transmitted by the bite of a sand fly. The disease results in sores on the skin, which can sometimes become severe and disfiguring. There is no vaccine for the disease and the limited drugs available often fail to provide a complete cure.
Curious about the influence of the skin microbiome on the disease, the Penn-led team swabbed the skin of 44 Leishmania patients, analyzing the microbiota not only of their lesions but also the area around them and a portion of skin on the opposite side of the bodies as the lesion. They noticed that the lesion samples contained less bacterial diversity than the samples of other skin sites. But not all of them were the same; they found three distinct community types: one dominated by Staphylococcus, one by Streptococcus and one that was mixed.
To get a clearer picture of how these microbiome shifts were connected to the disease, the researchers turned to a mouse model of Leishmania infection. Mirroring the findings in humans, the team found that infection with the Leishmania parasite induced a change in the skin microbiota in mice. They also found an association between the microbiota community type and disease severity. In mice that eventually resolved their infections, Staphylococcus dominated in the lesions, while Streptococcus was the dominant species in lesions on mice with a persistent, severe form of the disease.
A major discovery was that these shifts in microbiota were transmissible not only to other parts of the same mouse but to cage mates. When they kept mice infected with Leishmania in the same cage as uninfected mice for six weeks, the uninfected mice acquired a perturbed skin microbiome “profile” that resembled the infected mice.
The researchers hope to see whether the sharing of perturbed microbiota happens not just in mouse cages but also in households.
“I think an important next step will be to see if this sharing of microbiota occurs in people, and whether that could be a factor in affecting the severity of infections in humans,” Grice said.
A final question was to determine whether this naturally transmitted dysbiosis would predispose the uninfected animals’ response to an enhanced inflammatory response. And indeed, when infected with Leishmania, these mice had more severe inflammation and skin ulcers than mice with unperturbed skin microbiota. In a more general assay, the researchers used a contact hypersensitivity assay, which uses a skin irritant to elicit an immune response, on the mice that had been housed with Leishmania-infected mice. These dysbiotic mice, too, had a heightened inflammatory response.
To follow up on their findings, the researchers hope to examine whether sharing of a dysbiosis occurs in other infections and whether the resulting alteration in skin microbiota affect processes such as wound healing.
In addition, the Penn researchers will be working with their colleagues in Brazil to further examine the connections between the microbiome and leishmaniasis. Specifically, they hope to determine whether there is a connection between the type of skin microbiome present in Leishmania lesions and the severity of disease, or the responsiveness to treatment.
If true, “this may make us rethink the role of antibiotics in treating leishmaniasis,” Scott said.
Though previous studies are mixed about the effectiveness of antibiotics in alleviating the disease, additional information about the microbes that exacerbate inflammation could lead to more tailored therapies to tame skin lesions.
It turns out your skin is crawling with single-celled microorganisms — and they’re not just bacteria. A study by the Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the Medical University of Graz has found that the skin microbiome also contains archaea, a type of extreme-loving microbe, and that the amount of it varies with age.
The researchers conducted both genetic and chemical analyses of samples collected from human volunteers ranging in age from 1 to 75. They found that archaea (pronounced ar-KEY-uh) were most abundant in subjects younger than 12 and older than 60. Their study has been published in Scientific Reports (a Nature journal) in an article titled, “Human age and skin physiology shape diversity and abundance of Archaea on skin.”
“The skin microbiome is usually dominated by bacteria,” said Hoi-Ying Holman, director of the Berkeley Synchrotron Infrared Structural Biology (BSISB) Program and a senior author on the paper. “Most of the scientific attention has been on bacteria, because it’s easier to detect. Based on the literature, six years ago we didn’t even know that archaea existed on human skin. Now we’ve found they’re part of the core microbiome and are an important player on human skin.”
The study was a joint effort of Holman, Berkeley Lab postdoctoral fellow Giovanni Birarda (now a scientist at Elettra Sincrotrone Trieste in Italy), UC Berkeley postdoctoral fellow Alexander Probst (now associate professor at the University of Duisburg-Essen in Germany), and Christine Moissl-Eichinger, the corresponding author of the study. Moissl-Eichinger and her team at the Medical University of Graz in Austria and at the University of Regensburg in Germany analyzed the genetic features of the skin microbiomes.
In addition to the influence of age, they found that gender was not a factor but that people with dry skin have more archaea. “Archaea might be important for the cleanup process under dry skin conditions,” said Moissl-Eichinger. “The results of our genetic analysis (DNA-based quantitative PCR and next-generation sequencing), together with results obtained from infrared spectroscopy imaging, allowed us to link lower levels of sebum [the oily secretion of sebaceous glands] and thus reduced skin moisture with an increase of archaeal signatures.”
More than skin deep
It was not until the 1970s that scientists realized how different archaea were from bacteria, and they became a separate branch on the tree of life — the three branches being Bacteria, Archaea, and Eukarya (which includes all plants and animals). Archaea are commonly found in extreme environments, such as hot springs and Antarctic ice. Nowadays it is known that archaea exist in sediments and in Earth’s subsurface as well, but they have only recently been found in the human gut and linked with the human microbiome.
Holman’s focus is on developing synchrotron infrared spectroscopy techniques to look at biological or ecological systems. Using Berkeley Lab’s Advanced Light Source (ALS), one of the world’s brightest sources of infrared beams, the Holman Group developed a rapid and label-free method to screen cells and immediately tell if they’re bacteria or archaea.
“The challenges in microbial profiling are speed, throughput, and sample integrity,” she said. “We spent years developing this technique and could not have done it without the unique resources of the ALS.”
But the dearth of studies on skin archaea is not just because of technical limitations. The researchers assert that the lack of age diversity in the sampling in previous studies was also a factor. “Sampling criteria and methods matter,” Holman said. “We found middle-aged human subjects have less archaea; therefore, the archaeal signatures have been overlooked in other skin microbiome studies.”
From astronauts to archaea
This study stemmed from a planetary protection project for NASA and the European Space Agency. “We were checking spacecraft and their clean rooms for the presence of archaea, as they are suspected to be possible critical contaminants during space exploration — certain methane-producing archaea, the so-called methanogens, could possibly survive on Mars,” Moissl-Eichinger said. “We did not find many signatures from methanogens, but we found loads of Thaumarchaeota, a very different type of archaea that survives with oxygen.”
At first it was thought the Thaumarchaeota were from the outside, but after finding them in hospitals and other clean rooms, the researchers suspected they were from human skin. So they conducted a pilot study of 13 volunteers and found they all had these archaea on their skin.
As a follow-up, which is the current study, they tested 51 volunteers and decided to get a large range in ages to test the age-dependency of the archaeal signatures. Samples were taken from the chest area. The variations in archaeal abundance among the age groups were statistically significant and unexpected. “It was surprising,” Holman said. “There’s a five- to eightfold difference between middle-aged people and the elderly — that’s a lot.”
Role in human health still a question
Their study focused on Thaumarchaeota, one of the many phyla of archaea, as little evidence of the others was found in the pilot study. “We know that Thaumarchaeota are supposed to be an ammonia-oxidizing microorganism, and ammonia is a major component of sweat, which means they might play a role in nitrogen turnover and skin health,” Holman said.
In collaboration with Peter Wolf of the Medical University of Graz, the team also correlated archaeal abundance with skin dryness, as middle-aged persons have higher sebum levels and thus moister skin than the elderly.
So far, most archaea are known to be beneficial rather than harmful to human health. They may be important for reducing skin pH or keeping it at low levels, and lower pH is associated with lower susceptibility to infections.
“The detected archaea are probably involved in nitrogen turnover on skin, and are capable of lowering the skin pH, supporting the suppression of pathogens,” said Moissl-Eichinger. “Bacteria with the same capacities are already used as skin probiotics, potentially improving skin moisture and reducing body odors. Nevertheless, the clinical relevance of Thaumarchaeota remains unclear and awaits further studies.”
Holman listed several avenues of inquiry for future studies with Moissl-Eichinger. “We would like to investigate the physiological role of human skin archaea and how they differ from environmental archaea,” she said. “We would like to find out which niches they prefer on or in the human body. We also want to know whether they might be involved in pathogenic processes, such as neurodermatitis or psoriasis. So far, there is little evidence of the pathogenicity of archaea.”