The scientists of the “Biology and Mars Experiment” (BIOMEX) project had already sent kombucha cultures to the International Space Station (ISS) in 2014 with the support of the European Space Agency. The aim was to learn more about the robustness of cellulose as a biomarker, the genomic architecture of kombucha, and its survival behaviour under extraterrestrial conditions. After one and a half years under simulated Martian conditions outside the ISS, the samples were reactivated on Earth and cultivated for another two and a half years.

The head of the University of Göttingen’s Institute of Veterinary Medicine, Professor Bertram Brenig, was responsible for the sequencing and bioinformatic analysis of the metagenomes of the reactivated cultures and individual kombucha cultures in a team with researchers from the University of Minas Gerais in Brazil. “Based on our metagenomic analysis, we found that the simulated Martian environment drastically disrupted the microbial ecology of kombucha cultures. However, we were surprised to discover that the cellulose-producing bacteria of the genus Komagataeibacter survived.” The results suggest that the cellulose produced by the bacteria is probably responsible for their survival in extraterrestrial conditions. This also provides the first evidence that bacterial cellulose could be a biomarker for extraterrestrial life and cellulose-based membranes or films could be a good biomaterial for protecting life and producing consumer goods in extraterrestrial settlements.

Another interesting aspect of these experiments could be the development of novel drug delivery systems, for example for the development of medicine suitable for use in space. Another focus was on investigations into changes in antibiotic resistance: the research team was able to show that the total number of antibiotic and metal resistance genes — meaning that these microorganisms might survive despite antibiotics or metals in the environment — were enriched in the exposed cultures. “This result shows that the difficulties associated with antibiotic resistance in medicine in space should be given special attention in the future,” the scientists said.

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The federally funded review, which will be updated on an ongoing basis, was published today in the Annals of Internal Medicine.

Researchers did find evidence to support a short-term benefit in treating neuropathic pain — caused by damage to peripheral nerves, such as diabetic neuropathy resulting in pain described as burning and tingling, involving two FDA-approved synthetic products with 100% tetrahydrocannabinol, or THC: dronabinol (under the trade name Marinol) and nabilone (Cesamet). Both products also lead to notable side effects including sedation and dizziness, according to the review.

Another product, a sublingual spray of equal parts THC and cannabidiol, or CBD, extracted from the cannabis plant, known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain, although that product is not available in the U.S. This product also led to side effects, such as nausea, sedation and dizziness.

“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, Pharm.D., emeritus professor of medical informatics and clinical epidemiology in the OHSU School of Medicine. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.

“Unfortunately, there is very little scientifically valid research into most these products,” she said. “We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”

Voters in Oregon, Washington and 20 other states have legalized medical and recreational marijuana, however the researchers found many of the products now available at U.S. dispensaries have not been well studied.

“For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations,” the authors write.

This situation makes it difficult to guide patients.

“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” said co-author Roger Chou, M.D., director of OHSU’s Pacific Northwest Evidence-based Practice Center. “That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another.”

The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes “clinician briefs” to help health care workers translate the clinical implications.

“This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge,” said co-author Devan Kansagara, M.D., M.C.R., professor of medicine in the OHSU School of Medicine and a staff physician at the VA Portland.

Reviewers searched more than 3,000 studies in the scientific literature as of January of this year and landed on a total of 25 with scientifically valid evidence — 18 randomized controlled studies and seven observational studies of at least four weeks.

The effects of cannabis and related products are based on their ability to mimic the body’s own endocannabinoid system. The system is composed of receptors and enzymes in the nervous system that regulate bodily functions and can affect the sensation of pain. In the evidence review, researchers sorted the types of product into high, comparable and low ratios of THC to CBD and compared their reported benefits and side effects.

Dronabinol and nabilone fit into the high THC to CBD ratio category, with 100% THC (no CBD), showing the most benefit among the products studied, with meta-analysis of the six randomized controlled studies demonstrating statistically valid benefits for easing neuropathic pain compared to a placebo.

“Honestly, the best advice is to talk to your primary care physician about possible treatments for chronic pain,” McDonagh said. “If you want to consider cannabis, you need to talk to your doctor.”

In addition to McDonagh, Chou and Kansagara, co-authors included Benjamin J. Morasco, Ph.D., Jesse Wagner, M.A., Azrah Y. Ahmed, B.A., and Rongwei Fu, Ph.D.

The project was funded by Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services, contract number 75Q80120D00006. Statements in the report should not be construed as endorsement by the AHRQ or the Department of Health and Human Services.

The National Cancer Institute cites infection with H. pylori as the primary identified cause of certain types of stomach cancer. H. pylori is a bacterium that grows in the mucosa, or membrane layer that lines the stomach.

“This study is proposing that if you are carrying this particular allele, you are more likely to have an aggressive type of response to the bacteria that can result in complications,” said the study’s senior author, Juanita L. Merchant, MD, PhD, Regents Professor of Medicine and chief of the Division of Gastroenterology at the UArizona College of Medicine — Tucson.

In the United States, H. pylori is more prevalent in Hispanics, African Americans and the elderly. Dr. Merchant cited data suggesting that 1-3% of people with H. pylori will develop gastric cancer and that the cure rate is around 30%, which is low compared with some other types of cancer.

Current diagnosis of stomach or gastric cancer requires the patient to undergo an upper endoscopy, where a doctor looks for signs of cancer and takes a tissue sample for analysis.

For years, Dr. Merchant and colleagues have been investigating new ways to diagnose stomach cancer in its earliest possible stages. In 2020, they published research on a promising biomarker that appears in some patients before stomach cancer develops.

The new study focused on the molecular pathways that control the activation of immune cells in response to H. pylori infection, specifically the action of toll-like receptor 9 (TLR9).

Located within immune cells, TLR9 signals the immune system when to fight an infection. However, H. pylori infection can constantly trigger TLR9 activation over long periods of time, leading to the chronic inflammation. The long-term presence of inflammation caused by H. pylori infection is believed to be one of the triggers for cancer developing in the stomach.

“This addresses the question of what role the immune microenvironment has in gastric cancer,” said Dr. Merchant, who is a research member of the UArizona Cancer Center. “We have shown that these immune cells do play an important role.”

Researchers found that the chronic activation of TLR9 in the stomach triggers a series of events that includes increased production of interferon α, a signaling protein that can change the genetic signature of specialized immune cells known as myeloid-derived suppressor cells, or MDSCs. Prior research has linked MDSCs with H. pylori infection.

Dr. Merchant and her team focused on each step of the pathway and identified a specific genetic change — allele rs5743836 TLR9 minor C — that was linked to higher levels of TLR9 and interferon α and a greater incidence of gastric tumors. The allele is a single nucleotide polymorphism, or SNP, which is a genetic change in the DNA between genes.

“Because TLR9 and the SNP can be tested by DNA, they could be used as biomarkers to help us identify which patient populations are going to be more susceptible to the cellular changes that might lead to cancer based on their genetic background,” Dr. Merchant explained. “Those are the patients who could benefit from increased endoscopic surveillance.”

Eventually, the findings may also lead to new therapeutic options for patients.

“We have previously found a real-time biomarker in a blood test, and now we have something we can see in DNA,” Dr. Merchant said. “Our next step is to look at therapy options.”