Clinical applications of postbiotics in the treatment of Helicobacter infections

(Kyoto, 1 June 2018) Nitto Pharma, Kyoto, Japan publishes the inaugural issue of the Nitto Pharma e-Bulletin offering insights into the company’s activities on probiotics research for healthcare. The inaugural May 2018 issue includes video feature articles of Managing Director and Head of R&D, Kohey Kitao and research scientist Yasunori Yonejima; Research Highlights on ‘Clinical application of postbiotics in the treatment of Helicobacter infections’ and ‘Advances in postbiotics research for healthcare’. The May 2018 Nitto Pharma eBulletin also updates on news and events.

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May 2018 issue of the Nitto Pharma eBulletin

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Video feature articles
Kohey Kitao / Managing Director and Head of R&D, Nitto Pharma

Video feature articles
Yasunori Yonejima / Research Scientist, Nitto Pharma

Research Highlights
Clinical application of postbiotics in the treatment of Helicobacter infections

http://nitto-pharma-ebulletin.jp/research


Caption: Liquid HYA

HYA-fatty acid combats bacterial gastric diseases in mouse model experiments

The human digestive system is host to many kinds of bacteria: some friendly, probiotics types, and other kinds that are harmful. Identifying metabolic processes that can differentiate between these two types of bacteria is important to develop treatments for diseases caused by unfriendly bacteria.

Menaquinone (MK) a molecular compound produced by bacteria in the gut that can be synthesized by two different pathways. Of the two, the ‘futalosine pathway’ is not present in most probiotics. Researchers have studied this difference between the two kinds of bacteria and discovered molecules that only block the futalosine pathway, thereby inhibiting MK synthesis in harmful bacteria. Dietary fatty acids are an example of molecules exhibiting such blocking properties.

Polyunsaturated fatty acids are an integral component of the human diet and have many different structures. Of these, omega-3 and omega-6 fatty acids have especially stood out because of their health benefits for the heart and brain. Furthermore, in model experiments using mice, a team of researchers at Kitasato University, Japan, showed the ability of these fatty acids to diminish colonies of the bacteria Helicobacter pylori that causes gastric diseases. Their findings showed that some omega-3 and omega-6 fatty acids could block the futalosine pathway in H. pylori and greatly reduce the presence of H. pylori in the digestive tract of mice.

Recently, this team reported on a novel fatty acid: 10- hydroxy- cis- 12- octadecenoic acid (HYA), that is synthesized by gastrointestinal microbiota in the body. HYA is formed from linoleic acid (an omega-6 acid) by bacterial conversion. The researchers first measured the effects of HYA on H. pylori colonies grown in culture plates, and found that HYA suppressed many different strains of the bacteria. These effects were however not seen when MK was artificially added to the medium, implying that blocking MK synthesis was its mechanism of action.

These effects were then extended to two different mouse models of infection. When mice infected with H. pylori were fed with water containing HYA for three weeks, they were much less prone to gastric infections. Notably, HYA was also the most effective in preventing infection compared to other fatty acids. The bacteria Helicobacter is cause a form of gastric cancer, and mice infected with H. suis showed significantly less cancerous tissue and tumour markers over a six month trial after HYA treatment.

The authors are optimistic that, “daily supplementation with HYA, a hydroxy monounsaturated fatty acid, would prevent Helicobacter- associated gastric diseases through its antibacterial activity.” It’s remarkable how something synthesized by one member of the bacterial species can be used to fight other members of the same species.

Reference
Hidenori Matsui, Tetsufumi Takahashi, Somay Y. Murayama, Marina Kawaguchi, Koichi Matsuo, Masahiko Nakamura.“Protective efficacy of a hydroxy fatty acid against gastric Helicobacter infections.” Helicobacter, 22, e12430, (2017).

Published online August 2017
DOI: 10.1111/hel.12430.
https://doi.org/10.1111/hel.12430

Advances in postbiotics research for healthcare
http://nitto-pharma-ebulletin.jp/research/advances-in-probiotics-research-for-healthcare.html

Caption: Graph showing changes in blood glucose level in all subjects after ingestion

Clinical trials with fatty acid (HYA) derived from probiotic bacteria show potential health benefits in treating metabolic disorders.

Metabolic syndrome is a set of conditions including obesity and hypertension that could potentially lead to heart disease and diabetes. Reported cases of metabolic syndrome worldwide are rising due to changes in diets, insufficient physical exercise, and work related stress induced.

Research on metabolic syndrome often focusses on postprandial hyperglycemia—the state of high blood sugar in the body after eating a meal that has harmful effects on the body, including blocking blood vessels and increasing risks of heart attack. These cumulative risks are referred to as ‘hidden diabetes’ and there are increasing demands for new approaches to both prevent and treat hyperglycemia as concerns grow about metabolic syndrome in public health.

Now, 10- hydroxy- cis- 12- octadecenoic acid (HYA) is a fatty acid derived due to the metabolic action of lactic acid bacteria. These ‘friendly’ bacteria are referred to as ‘probiotics’ because the products of their metabolism in the human digestive system have potential health benefits for treating human aliments. Notably, such probiotic bacteria are found in food such as yogurt, kefir, and Japanese miso soup. Furthermore, in experiments using mice, HYA prevented colon conditions including colitis. With this background, researchers at Nitto Pharmaceutical Industries Ltd (Nitto Pharma), Kyoto, Japan are exploring the potential of using HYA for the prevention and treatment of diabetes and other metabolic disorders.

In a recent study, the researchers selected a cohort of 60 male and female subjects with a propensity for postprandial hyperglycemia. The subjects were given capsules containing either low or high doses of HYA or placebos followed by regimented meals, once a week for three weeks. The subjects received a different treatment each week to ensure that each subject received all three treatments. Finally, the researchers measured the blood glucose and insulin levels before and after 30, 60, 90, 120 minutes of consuming meal.

Team leader Yasunori Yonejima, at Nitto Pharma, and his colleagues observed that the blood glucose levels were much lower for subjects who had taken both doses of HYA than people from placebo groups. These effects were observed within 30 minutes and lasted for up to 60 minutes. Glucose levels after 60 minutes saturated in all subjects and Insulin levels were also lower for both HYA treatments at the same measurement time intervals.

On the other hand, transient adverse events were observed in just 5 subjects, suggesting HYA to be safe for consumption at the doses used in these clinical trials.

“These results suggest that HYA can inhibit the elevation of postprandial blood glucose levels and may have the effect in preventing diabetes mellitus”, the authors conclude. Since HYA is synthesized from a dietary fatty acid by well classified probiotic bacteria, the importance of the composition of gut bacteria and diet in combatting metabolic syndrome is another important finding from this research.

Reference
Yasunori Yonejima, Masato Urushihara, Kohei Kitao, Kenichi Furihata. Effects of the Intake of HYA-containing Food on Postprandial Hyperglycemia: A Randomized, Placebo-controlled, Double-blind Crossover Trial. Progress in Medicine, 37:1105–1111, (2017).



Caption: Graph showing changes in blood glucose level in all subjects after ingestion

News
Nitto Pharma participates at The American Oil Chemists’ Society (AOCS) meeting, 6-9 May 2018, Minneapolis Convention Center, Minneapolis, Minnesota, USA.
http://nitto-pharma-ebulletin.jp/news/nitto-pharma-kyoto-headquarters.html Nitto Pharma participates in AAAS Science Webinar on 8 August 2018
http://nitto-pharma-ebulletin.jp/news/nitto-pharma-participates-in-aaas-science-webinar-on-8-august-2018.html
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Further information
Public Relations & Design Section
Nitto Pharmaceutical Industries, Ltd.,
35-3 Minamibiraki, Kamiueno-cho, Muko 617-0006, Japan
Email: pr@nitto-ph.com
Phone: +81-75-921-5303

About Nitto Pharmaceutical Industries, Ltd. (Nitto Pharma), Kyoto, Japan
Established in 1947, Nitto Pharma is located in a quiet residential area about 30-minutes by train from Kyoto Station. The company is surrounded by narrow cobbled streets lined with Sakura trees and the view from the entrance of the company’s premises is one of carefully mown lawns surrounded by many varieties of flowers and plants. Visitors find the view more like a flower garden than the hub of cutting-edge research at one Japan’s leading biopharmaceutical companies.

The nature and beauty of our premises underscores the company’s of motto of being a ‘Family-friendly Company’ aiming to contribute to the wellbeing of our employees and humanity’s health and happiness. This is the philosophy at the heart of the ‘NOSTER’ brand for biopharmaceutical medicinal and nutritional products.

Nitto Pharma has always believed that they “want to save people as many people as possible who are ill, with the power of microorganisms”. Nitto Pharma has confidence that they can achieve this goal if they can extract the limitless power possessed by microorganisms. The global biotechnology brand ‘NOSTER’ is the driving force for advancing this believe.

The NOSTER brand underscores the desire of all the staff at Nitto Pharma—an innovative biopharmaceutical company based in Kyoto, Japan—to contribute to the treatment of people suffering from diseases. Nitto Pharma has continued to conduct research and development of microorganisms since 1947 in cooperation with many kinds of universities and research institutes based on the stance that microorganisms have a lot to teach us about what is good for the human body that they have helped create.

Human beings maintain life with amazing balance, but it is not appreciated that it is the close complementary relationship with microorganisms that plays an important role in maintaining this balanced life. For Nitto Pharma the deep recognition that microorganisms are indispensable partners for healthy living is “our origin”; a belief that will never change.