Balancing good and bad bacteria in the gut
IgA antibodies are watchdog proteins constantly evolving to keep gut bacteria in check
The human gut is lined with a mucous-filled coating which harbors immune cells. These mucosal cells fight orally ingested microbes with a specific kind of antibody called IgA. Somatic hypermutation (SHM) is a process which enables the constant production of different forms of IgA to fight unknown microbes. However, the effects of SHM in the gut are unclear. Now, Reiko Shinkura, Tasuku Honjo, and colleagues have shown that SHM empowers IgA to effectively regulate gut bacteria.
The researchers curtailed SHM in mice to first assess changes in IgA. Aicda, a gene facilitating SHM was mutated to achieve this. While the resulting mutant mice had a normal rate of IgA production, they didn’t show high-affinity forms of IgA.
Signs of immune hyperactivation were subsequently observed in these mice—sites of antibody synthesis started swelling, accompanied by imbalances in the normal bacterial composition of the gut. When these mice ingested infectious bacteria, the bacteria easily infiltrated their tissues. Similar observations were seen when the mice were infected with the cholera toxin, resulting in enhanced susceptibility to the disease. Thus, without high-affinity forms of IgA there were severe impairments in the mucosal defense system.
SHM enables IgA antibodies to evolve and ward off harmful foreign bacteria while maintaining friendly bacteria within the gut.
References
1. M. Wei et al., Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nat Immunol 12, 264–270 (2011). DOI: https://doi.org/10.1038/ni.1991
2. S. Okai et al., Intestinal IgA as a modulator of the gut microbiota, Gut Microbes, 8:5, 486-492, (2017). DOI: 10.1080/19490976.2017.1310357
Gut microbiota and heart disease
Two groups of bacteria found in the human gut show potential for preventing coronary
Coronary artery disease (CAD) is a blockage of the blood vessels resulting in heart damage and is one of the leading causes of death worldwide. Research has shown that bacteria present in the human gut are linked to CAD. However, the specific type of bacteria involved and their exact role is still unclear. A research group led by Tomoya Yamashita from Kobe University has now uncovered this link based on their observations in patients with CAD.
The researchers found that patients with CAD had a reduced presence of two specific bacterial groups (Bacteroides vulgatus and Bacteroides dorei) in their gut compared to patients without CAD. To understand the role of these bacteria better, CAD-prone mice were orally ingested with the bacteria. The blood vessels of the mice showed a reduction in the number of blockages. They also showed lower levels of lipopolysaccharide (LPS), a toxin that causes cardiovascular inflammation. Notably, the CAD patients had high levels of LPS in their gut. Hence, the presence of Bacteroides vulgatus and Bacteroides dorei was linked to cardio-protection by preventing LPS accumulation and the resulting inflammation it causes.
Patients with diabetes and hypertension are often at a very high risk of developing CAD. Treatment with these bacteria could help prevent such individuals from acquiring the fatal condition.
Reference
Yoshida, N., Emoto, T., Yamashita, T., Watanabe, H., Hayashi, T., Tabata, T., Hoshi, N., Hatano, N., Ozawa, G., Sasaki, N., Mizoguchi, T., Amin, H.Z., Hirota, Y., Ogawa, W., Yamada, T., Hirata, KI. Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis. Circulation. 138:2486–2498, (2018).
Clinical application of postbiotics in the treatment of Helicobacter infections
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.
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 suis 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 Matsui1, Tetsufumi Takahashi(2), Somay Y. Murayama(3), Marina Kawaguchi(4), Koichi Matsuo(5), Masahiko Nakamura(6) .“Protective efficacy of a hydroxy fatty acid against gastric Helicobacter infections.” Helicobacter, 22, e12430, (2017)
Technology for culturing gut microorganisms developed by NOSTER
Source: Noster Inc
It is said that more 1000 types, totaling 100 trillion microorganisms coexist in the human gut, and as most of them live in an oxygen-free environment it is difficult to culture them in natural environments.
To overcome this problem NOSTER has developed innovative microdroplet technology to separate live intestinal bacteria from the fecal suspension in a droplet approximately 50 micrometers n diameter and culture them under conditions suitable for each intestinal microorganism. NOSTER is using this culturing technology to construct a library of over 1000 strains of intestinal microorganisms.
LEUCOSACCHARIDE® – an indigestible dietary fiber produced by NOSTER Inc
Source: Noster Inc
Leucosaccharide is an exopolysaccharide produced by Leuconostoc mesenteries , one microorganism from Noster’s library, and is a special indigestible dietary fiber derived from gut microorganisms produced by assimilating sucrose.
So far, it has been confirmed that it promotes the secretion of IgA antibodies that enhance the immunity of the intestinal mucosa and reduces symptoms of chronic skin disease known as “psoriasis”. In addition, compared to other dietary fibers, it has the function of producing large amounts of short-chain fatty acids in the intestine, and has also been found to suppress increases in weight. Furthermore, to enhance immunity, leucosaccharides may lead to the prevention of diseases associated with lifestyle-related diseases such as obesity, and we are pursuing research and development on their use as new functional materials.
