Tag Archives: Stomach

Microbiology

Japanese natto consumption may help realize a healthy and longer-living society

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Reviewed by Lily Ramsey, LLMMay 26 2023

Health is wealth as the saying goes and new research now shows that it is possible to have a healthy, less stressed society through familiar and inexpensive foods. One such food might be the Japanese natto which is made from softened soybeans that have been boiled or steamed and fermented with a bacteria called Bacillus subtilis var. natto. Bacillus subtilis var. natto is found in soil, plants, animals, and the human stomach and intestines. Most of the natto consumed in Japan is made from the Miyagino strain.

A research group led by Professor Eriko Kage-Nakadai at the Graduate School of Human Life and Ecology, Osaka Metropolitan University, examined the effects of Bacillus subtilis var. natto consumption on the lifespan of the host using Caenorhabditis elegans worms. The researchers found that Caenorhabditis elegans fed Bacillus subtilis var. natto had a significantly longer lifespan than those fed the standard diet, and further elucidated that the p38 MAPK pathway and insulin/IGF-1-like signaling pathway, which are known to be involved in innate immunity and lifespan, were involved in the lifespan-enhancing effects of Bacillus subtilis var. natto. They also examined stress tolerance, which has been shown to have a correlation with longevity, and found that resistance to UV light and oxidative stress is enhanced.

For the first time, we were able to demonstrate the possibility of lifespan-extending effects of Caenorhabditis elegans through the ingestion of Bacillus subtilis var. natto. We hope that future experiments on mammals and epidemiological studies will help to realize a healthy and longer-living society if we can apply this research to humans.”

Professor Eriko Kage-Nakadai, Graduate School of Human Life and Ecology, Osaka Metropolitan University

The research results were published online in the Journal of Applied Microbiology on April 20, 2023.

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Source:

Osaka Metropolitan University

Journal reference:

Teramoto, N., et al. (2023) Impacts of Bacillus subtilis var. natto on the lifespan and stress resistance of Caenorhabditis elegans. Journal of Applied Microbiology. doi.org/10.1093/jambio/lxad082.

Microbiology

Discovery of Helicobacter’s Achilles heel offers great potential for the development of new drugs

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Reviewed by Emily Henderson, B.Sc.Apr 26 2023

LMU researchers have discovered a weakness in the bacterium Helicobacter pylori, which could be exploited to develop new drugs.

The pathogen Helicobacter pylori, which is responsible for widespread illnesses such as gastric ulcers and stomach cancer, has a weak point, which could be exploited to create new drugs. This was discovered by a research group led by LMU biologists Professor Rainer Haas and Dr. Wolfgang Fischer from the Max von Pettenkofer Institute of Hygiene and Medical Microbiology. Their results have now been published in the journal Cell Chemical Biology.

More than four billion people worldwide are infected with the stomach bacterium, leading to over 800,000 cases of stomach cancer every year. Because the bacterium is becoming increasingly resistant to current drugs, the World Health Organization (WHO) has classified it as a pathogen with high priority for the research and development of new antibiotics. New approaches and therapeutics are urgently required to replace or complement established treatment methods.

The new study has taken an important step in this direction. “We were able to demonstrate that the bacteria are very sensitive to certain substances that inhibit cellular respiration,” says Haas.

Fighting helicobacter and protecting the gut microbiome

The researchers were able to identify several compounds from various substance groups that incapacitate the respiratory chain of H. pylori even in small concentrations. For other useful bacteria, including representatives of the normal gut microbiome, these substances are unproblematic. These bacteria tolerate larger amounts of the substances.

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The authors of the study used a broad spectrum of biochemical and microbiological methods as well as molecular modeling techniques to discover why H. pylori reacts so sensitively to these substance groups. They identified the cause in a slightly modified structure of the so-called quinone binding pocket in respiratory complex I.

This Achilles heel offers great potential for the development of specifically tailored new active agents that could be used as pathogen blockers against H. pylori. “Our results reveal a surprising weakness in the metabolism of these bacteria, which are well adapted otherwise to their unusual environment,” says Fischer.

The research team at LMU was also able to identify possible mutations that would make the bacteria less sensitive to the inhibitors. However, these mutations also weaken the metabolism of the pathogens. This means that less resistance is formed to the complex I inhibitors.

“Overall, our results are very promising,” adds Haas. “We managed to identify a whole group of inhibitors that do not exhibit any cross-resistance with current therapeutics. They are less susceptible to the development of resistance and have a small impact on the gut microbiome.”

In addition to scientists at LMU, the German Center for Infection Research and researchers from Ghent University, the Max Planck Institute of Biophysics in Frankfurt, the Technical University of Munich, Helmholtz Munich and Helmholtz Braunschweig, Goethe University Frankfurt, and BASF Ludwigshafen all made significant contributions to the study.

Source:

Ludwig-Maximilians-Universitaet Muenchen (LMU)

Microbiology

Genetically-engineered probiotic could be a new way to reduce alcohol-induced health problems

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Reviewed by Emily Henderson, B.Sc.Apr 11 2023

Excessive alcohol consumption leads to painful hangovers and accompanying headaches, fatigue, and nausea. Drinking alcohol has also been linked to a raft of health problems in the human body, including heart disease, cirrhosis, and immune deficiency. One way to avoid those consequences would be to drink less, but researchers in China have introduced another way to mitigate hangovers and other adverse outcomes -; a genetically-engineered probiotic.

In a paper published this week in Microbiology Spectrum, the researchers described their approach and reported that in experiments on mice, the treatment reduced alcohol absorption, prolonged alcohol tolerance, and shortened the animals’ recovery time after exposure to alcohol. The probiotic hasn’t yet been tested on humans, but the authors predicted that if it confers the same benefits, it could present a new way to reduce alcohol-induced health problems, and liver problems in general.

Meng Dong, Ph.D, at the Chinese Academy of Science’s Institute of Zoology, who worked on the study, noted that clinical applications may extend beyond alcohol-related conditions. “We believe that genetically engineered probiotics will provide new ideas for the treatment of liver diseases,” she said.

The human body primarily uses forms of an enzyme called alcohol dehydrogenase, or ADH, to metabolize alcohol. But some variants are more effective than others: Some studies have found that a form called ADH1B, found primarily in East Asian and Polynesian populations, is 100 times more active than other variants. Previous studies on mice have shown that viral vectors genetically engineered to express ADH1B can accelerate the breakdown of alcohol, but that approach hasn’t been shown to be safe in humans.

Motivated by those findings, Dong and her colleagues looked for a safer delivery method, focusing on the probiotic Lactococcus lactis, a bacterium often used in fermentation. They used molecular cloning to introduce the gene for human ADH1B into a bacterial plasmid, which was then introduced into a strain of L. lactis. Lab tests confirmed that the probiotic secreted the enzyme. The researchers encapsulated the probiotic to ensure it would survive against stomach acid, then tested it on 3 groups of 5 mice, each exposed to different levels of alcohol.

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Untreated mice showed signs of drunkenness 20 minutes after exposure to alcohol. When the mice were placed on their backs, for example, they were unable to get back on their feet. But in the group that received a probiotic that expressed human ADH1B, half the mice were still able to turn themselves over an hour after alcohol exposure. A quarter never lost their ability to turn themselves over.

Further tests showed that 2 hours after exposure, blood alcohol levels in the control group continued to rise, while those in the probiotic-treated mice had begun to fall. In addition, the researchers found that treated mice showed lower levels of lipids and triglycerides in their livers, suggesting that the probiotic could alleviate alcohol-related damage to that organ.

The next step, Dong said, is to investigate whether the potential therapeutic effect of the modified probiotic extends to humans.

We are excited about the improvement of recombinant probiotics in acute alcohol-induced liver and intestinal damage.”

Meng Dong, Ph.D, Chinese Academy of Science’s Institute of Zoology

Source:

American Society for Microbiology

Journal reference:

Jiang, X., et al. (2023) Oral Probiotic Expressing Human Ethanol Dehydrogenase Attenuates Damage Caused by Acute Alcohol Consumption in Mice. Microbiology Spectrum. doi.org/10.1128/spectrum.04294-22.

Microbiology

Gut bacterial community found to be less diverse in people with irritable bowel syndrome

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Reviewed by Emily Henderson, B.Sc.Jan 19 2023

People with irritable bowel syndrome (IBS) have lower bacterial diversity in the intestine than do healthy people, according to a team of Korean investigators. The investigators believe that theirs is the first analysis to find a clear association between IBS and reduced diversity in the microbiota of the gut. The research appears in Microbiology Spectrum, an open-access journal of the American Society for Microbiology.

Normally, “More than 10,000 species of microorganism live in the human intestine,” said corresponding author Jung Ok Shim, M.D., Ph.D., professor of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Korea University College of Medicine, Seoul. Disruption of the microbiome of the human gastrointestinal tract can trigger IBS. Typically, IBS causes bloating, diarrhea, and stomach pain or cramps.

Previous studies of gut bacteria in patients with IBS have been controversial, with inconsistent results, due to small sample size and lack of consistent analytical methods used among these studies, said Shim. The investigators combined their own dataset with 9 published, shared datasets, encompassing 576 IBS patients and 487 healthy controls, analyzing them with a “unified data processing and analytical method.”

The researchers found that the gut bacterial community is less diverse in IBS patients than in healthy people, said Shim. Additionally, the abundance of 21 bacterial species differed between IBS patients and healthy controls. However, the findings were not statistically significant in the pediatric cohort due to small sample size.

The investigators proved that the disturbed gut bacterial community “is associated with IBS, though this does not mean that the relationship is causal,” said Shim. “Functional studies are needed to prove whether the change in gut micro-organisms contributes to development of IBS.”

Even though IBS is a common disorder, its pathogenesis remains unknown, and as yet there is no effective treatment strategy. “Based on the epidemiological studies of IBS patients, altered gut microbiota was proposed as one of the possible causes of IBS,” the researchers write. “Acute bacterial gastroenteritis can cause chronic, asymptomatic, low-grade intestinal wall inflammation sufficient to alter neuromuscular and epithelial cell function.”

Source:

American Society for Microbiology

Journal reference:

Kim, G-H., et al. (2023) Gut Bacterial Dysbiosis in Irritable Bowel Syndrome: a Case-Control Study and a Cross-Cohort Analysis Using Publicly Available Data Sets. Microbiology Spectrum. doi.org/10.1128/spectrum.02125-22.

Microbiology

1 in 7 Americans – Most People Don’t Seek Care for This Shockingly Common Condition

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According to a recent study conducted by Cedars-Sinai researchers, about 1 in 7 Americans suffer bloating on a weekly basis, yet the majority of them don’t seek medical attention for it. The findings were recently published in the journal Clinical Gastroenterology and Hepatology.

“Although bloating is a common symptom, some patients may not bring it up with their doctors,” said Janice Oh, MD, a resident physician within the Division of General Internal Medicine Division at Cedars-Sinai and first author of the study. “It’s important that people feel comfortable discussing bloating because it could be a symptom of a serious condition and there are treatments available.”

People who are bloated may feel tightness or swelling in the abdomen. It may occur when a person’s gastrointestinal tract fills with air or gas and is sometimes caused by diet or an underlying condition such as irritable bowel syndrome, carbohydrate enzyme deficiency, or chronic constipation.

To understand the scope of bloating in the U.S., the authors emailed a survey to nearly 90,000 people. Of the 88,795 people who completed the survey from May through June 2020, 12,324 (13.9%) reported bloating in the past seven days.

“To our knowledge, this is among the largest studies of bloating in the U.S.,” said Brennan Spiegel, MD, MSHS, director of Health Services Research at Cedars-Sinai and senior author of the study. “Anecdotally, we often hear about bloating in the clinic, but this study adds concrete evidence to describe how commonly it occurs and what other conditions it’s associated with.”

Of the people who reported experiencing bloating, about 58.5% said they have never sought care for their symptoms.

Some of the reasons they gave for not seeking care were that the bloating resolved on its own (32.5%), it wasn’t bothersome (29.9%), they were able to manage it with over-the-counter medications or lifestyle changes (20.8%), they didn’t have health insurance (10.2%) or time to go to the doctor (9%), or they weren’t comfortable discussing bloating with a healthcare provider (8.5%).

Women were also more than twice as likely as men to report bloating.

“Other studies have also found that women report more bloating than men, and researchers have proposed various hypotheses for why this may be occurring,” Oh explained. “These include hormonal, metabolic, psychosocial, lifestyle and dietary differences between men and women.”

Latinos and people under the age of 60 were also more likely to report bloating within the past seven days, as were people with medical conditions such as irritable bowel syndrome, chronic constipation, and ulcerative colitis. People with related gastrointestinal symptoms, such as abdominal pain and excess gas, were also more likely to experience bloating.

“Bloating can often be managed effectively with various medications, such as gut-directed antibiotics or treatments that affect serotonin levels in the gut. There is also evidence that lifestyle changes can help, including exercise, such as core strengthening, as well as dietary changes, but it requires discussion with a healthcare provider about what might be causing the bloating,” Oh said.

More studies are needed to investigate the causes of bloating and how to best treat it, according to the investigators.

Reference: “Abdominal Bloating in the United States: Results of a Survey of 88,795 Americans Examining Prevalence and Healthcare Seeking” by Janice E. Oh, William D. Chey and Brennan Spiegel, 14 November 2022, Clinical Gastroenterology and Hepatology.
DOI: 10.1016/j.cgh.2022.10.031

The study was funded by Ironwood Pharmaceuticals.

Cedars-Sinai Medical Center

Microbiology

Research findings could bolster the effectiveness of immune-checkpoint therapy

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Reviewed by Emily Henderson, B.Sc.Nov 16 2022

Immune checkpoint inhibitors such as Keytruda and Opdivo work by unleashing the immune system’s T cells to attack tumor cells. Their introduction a decade ago marked a major advance in cancer therapy, but only 10% to 30% of treated patients experience long-term improvement. In a paper published online today in The Journal of Clinical Investigation (JCI), scientists at Albert Einstein College of Medicine describe findings that could bolster the effectiveness of immune-checkpoint therapy.

Rather than rally T cells against cancer, the Einstein research team used different human immune cells known as natural killer (NK) cells-;with dramatic results.

We believe the novel immunotherapy we’ve developed has great potential to move into clinical trials involving various types of cancer.”

Xingxing Zang, M.Med., Ph.D., Study Leader

Xingxing Zang is the the Louis Goldstein Swan Chair in Cancer Research and professor of microbiology & immunology, of oncology, of urology, and of medicine at Einstein and a member of the Cancer Therapeutics Program of the Montefiore Einstein Cancer Center.

Telling friend from foe

The surfaces of immune cells are studded with receptors known as “checkpoint” proteins, which prevent immune cells from straying beyond their usual targets (pathogen-infected cells and cancer cells). When checkpoint receptors on immune cells bind with proteins expressed by the body’s own normal cells, the interaction puts the brakes on a possible immune-cell attack. Diabolically, most types of cancer cells express proteins that bind with checkpoint proteins, tricking immune cells into standing down and not attacking the tumor.

Immune checkpoint inhibitors are monoclonal antibodies designed to short-circuit immune-cell/cancer-cell interactions by blocking either the tumor proteins or the immune-cell receptors that bind with tumor proteins. With no brakes to impede them, immune cells can attack and destroy cancer cells.

New focus on natural killer cells

The limited effectiveness of checkpoint inhibitors prompted Dr. Zang and other scientists to look at checkpoint pathways involving NK cells, which-;like T cells-;play major roles in eliminating unwanted cells. A cancer-cell protein called PVR soon captured their attention. “We realized that PVR may be a very important protein that human cancers use to hobble the immune system’s attack,” said Dr. Zang.

PVR protein is usually absent or very scarce in normal tissues but is found in abundance in many types of tumors including colorectal, ovarian, lung, esophageal, head and neck, stomach, and pancreatic cancer as well as myeloid leukemia and melanoma. Moreover, PVRs appeared to inhibit T cell and NK cell activity by binding to a checkpoint protein called TIGIT-;prompting efforts to interrupt the TIGIT/PVR pathway by using monoclonal antibodies made against TIGIT. More than 100 clinical trials targeting TIGIT are now in progress worldwide. However, several clinical studies including two large phase 3 clinical trials have recently failed to improve cancer outcomes.

Recognizing the role of a new receptor

Meanwhile, the cancer-cell protein PVR was found to have another “binding partner” on NK cells: KIR2DL5. “We hypothesized that PVR suppresses NK cell activity not by binding with TIGIT but by binding with the recently recognized KIR2DL5,” said Dr. Zang. To find out, he and his colleagues synthesized a monoclonal antibody targeting KIR2DL5 and carried out in vitro and in vivo experiments using the antibody.

In their JCI paper, Dr. Zang and colleagues demonstrated that KIR2DL5 is a commonly occurring checkpoint receptor on the surface of human NK cells, which PVR cancer proteins use to suppress immune attack. In studies involving humanized animal models of several types of human cancers, the researchers showed that their monoclonal antibody against KIR2DL5-;by blocking the KIR2DL5/PVR pathway-;allowed NK cells to vigorously attack and shrink human tumors and prolong animal survival (see accompanying illustration). “These preclinical findings raise our hopes that targeting the KIR2DL5/PVR pathway was a good idea and that the monoclonal antibody we’ve developed may be an effective immunotherapy,” said Dr. Zang.

Einstein has filed a patent application for KIR2DL5/PVR immune checkpoint including antibody drugs and is interested in a partnership to further develop and commercialize the technology.

Dr. Zang has previously developed and patented more than 10 immune checkpoint inhibitors. One of those inhibitors is now being tested in China in phase 2 clinical trials involving several hundred patients with advanced solid cancers (non-small cell lung cancer, small cell lung cancer, nasopharyngeal cancer, head and neck cancer, melanoma, lymphoma) or recurrent/refractory blood cancers (acute myeloid leukemia, myelodysplastic syndromes). Another of Dr. Zang’s immune checkpoint inhibitors will be evaluated starting next year in cancer clinical trials in the United States.

Source:

Albert Einstein College of Medicine

Journal reference:

Ren, X., et al. (2022) Blockade of the immunosuppressive KIR2DL5/PVR pathway elicits potent human NK cell-mediated antitumor immunity. Journal of Clinical Investigation. doi.org/10.1172/JCI163620.