Breaking News
February 19, 2019 - Customized Micropatterning for Improved Physiological Relevance
February 19, 2019 - Unique gene therapy approach paves new way to tackle rare, inherited diseases
February 19, 2019 - Activating gene that helps excite neurons reverses depression in male mice
February 19, 2019 - Science Puzzling Out Differences in Gut Bacteria Around the World
February 19, 2019 - Cells that destroy the intestine
February 19, 2019 - On recovery, vulnerability and ritual: An exhibit in white
February 19, 2019 - Scientific Duo Gets Back To Basics To Make Childbirth Safer
February 19, 2019 - COPD patients need more support when understanding new chest symptoms
February 19, 2019 - Using light-based method for production of pharmaceutical molecules
February 19, 2019 - Scientists find link between inflammation and cancer
February 19, 2019 - The High Cost Of Sex: Insurers Often Don’t Pay For Drugs To Treat Problems
February 19, 2019 - Hearing impairment associated with accelerated cognitive decline with age
February 19, 2019 - Researchers identify multiple genetic variants associated with body fat distribution
February 19, 2019 - Influenza and common cold are completely different diseases, study shows
February 19, 2019 - Scientists untangle how microbes manufacture key antibiotic compound
February 19, 2019 - Greater primary care physician supply associated with longer life spans
February 19, 2019 - HIV-1 protein suppresses immune response more broadly than thought
February 19, 2019 - For 2020 Dem Hopefuls, ‘Medicare-For-All’ Is A Defining Issue, However They Define It
February 19, 2019 - KU professor discusses promise of brain-computer interface to aid, restore communication
February 19, 2019 - Highly effective solution for detecting onset of aggregation in nanoparticles
February 19, 2019 - Early marker of cardiac damage triggered by cancer treatment identified
February 19, 2019 - Antidepressant drug could save people from deadly sepsis, research suggests
February 19, 2019 - CRISPR technology creates pluripotent stem cells that are ‘invisible’ to the immune system
February 19, 2019 - New study establishes how stress favors breast cancer growth and spread
February 19, 2019 - Midlife Systemic Inflammation Linked to Later Cognitive Decline
February 19, 2019 - Therapy derived from parasitic worms downregulates proinflammatory pathways
February 19, 2019 - Antimicrobial reusable coffee cups are less likely to become contaminated with bacteria, study shows
February 19, 2019 - Harnessing the evolutionary games played by cancer cells to advance therapies
February 19, 2019 - AHA News: Heart Transplant Survivor Gets Wedding Proposal at Finish Line
February 19, 2019 - HIV hidden in patients’ cells can now be accurately measured
February 19, 2019 - Research finds reasons for sudden cardiac death in patients with stable ischemic disease
February 19, 2019 - New protocol could help physicians to rule out bacterial infections in infants
February 19, 2019 - Women experiencing miscarriage should be offered treatment choices
February 19, 2019 - New protocol can help identify febrile infants at low risk for serious bacterial infections
February 19, 2019 - Innovative way to block HIV runs into a roadblock
February 19, 2019 - Springer Nature with BCRF conduct pilot project to make their research datasets more accessible
February 19, 2019 - Study finds neuromelanin-sensitive MRI as potential biomarker for psychosis
February 19, 2019 - Improvements in cardiovascular care for elderly save billions in health care costs
February 19, 2019 - Chilean food regulations are changing food perceptions and purchasing habits, study suggests
February 19, 2019 - Index endoscopy results are crucial for assessment of Barrett’s patients
February 18, 2019 - Breast cancer screening age should be lowered to 35
February 18, 2019 - Brain synchronization depends on the language of communication
February 18, 2019 - Drug Company Payments Over Time May Influence Rx Practices
February 18, 2019 - Despite socioeconomic gains, black-white ‘health gap’ remains
February 18, 2019 - Researchers report progress in the treatment of aggressive brain tumors
February 18, 2019 - Scientists discover trigger that turns strep infections into devastating disease
February 18, 2019 - Scanning children’s teeth may predict future mental health issues
February 18, 2019 - Health Highlights: Feb. 14, 2019
February 18, 2019 - New knowledge could help predict and prevent depression
February 18, 2019 - More primary care physicians leads to longer life spans | News Center
February 18, 2019 - Study examines link between supply of primary care physicians and life expectancy
February 18, 2019 - New study assesses screen time in young children
February 18, 2019 - Patented IU discovery to treat ARDS has been optioned to Theratome Bio
February 18, 2019 - Software found to be four times better at monitoring ovarian cancer
February 18, 2019 - Male Y chromosomes not ‘genetic wastelands’
February 18, 2019 - Hormone therapy during gender transition may increase risk for cardiovascular events
February 18, 2019 - NICE renews accreditation for Advanced
February 18, 2019 - FDA Grants Orphan Drug Designation to Amplyx Pharmaceuticals for APX001 for Treatment of Cryptococcosis
February 18, 2019 - Molecule effective in killing tuberculosis bacteria
February 18, 2019 - Columbia researchers unravel why some glioblastomas respond to immunotherapy
February 18, 2019 - Men who are able to do ten push-ups are less likely to have a stroke
February 18, 2019 - Blood-brain barrier disruption could lead to age-related cognitive decline
February 18, 2019 - Combination of PARP inhibitor and immunotherapy results in tumor regression in SCLC mouse models
February 18, 2019 - Heavy smoking could lead to vision loss, study finds
February 18, 2019 - New diagnostic test for malaria uses spit, not blood
February 18, 2019 - New therapeutic molecules show promise in reversing memory loss related to depression, aging
February 18, 2019 - Darla Shine joins anti-vaccination campaigners
February 18, 2019 - New study outlines sex-specific issues in ischemic heart disease
February 18, 2019 - Drug combinations could become first-line treatment for metastatic kidney cancer
February 18, 2019 - Lifetime adversity, increased neural processing during trauma combine to intensify core PTSD symptoms
February 18, 2019 - HRQoL Scores Decrease With Treatment Line in Multiple Myeloma
February 18, 2019 - Convincing evidence that type 2 diabetes is a cause of erectile dysfunction
February 18, 2019 - Study offers implications of advanced age in evaluation, management of ischemic heart disease
February 18, 2019 - Children from homes with flame-retardant sofa have high SVOC concentration in their blood
February 18, 2019 - Art Institute of Chicago announces results of research on five terracotta sculptures
February 18, 2019 - New PET/CT tracer shows high detection rate for diagnosis of acute venous thromboembolism
February 18, 2019 - Smoking may blight immune response against melanoma and reduce survival
February 18, 2019 - How Inactivity and Junk Food Can Harm Your Brain
February 18, 2019 - Diabetes tops common conditions for frequent geriatric emergency patients
February 18, 2019 - Longer-lived sperm produces offspring with healthier lifespans
Understanding How Antibodies Shape the Gut Microbiome

Understanding How Antibodies Shape the Gut Microbiome

image_pdfDownload PDFimage_print

What function does IgA carry out in the human immune system?

IgA is the most abundant class of immunoglobulin in the human body, with an estimated 80% of the total plasma cells in our body being IgA+.

Image Credit: Kateryna Kon / Shutterstock

Secretory IgA plays an important role as a frontline defense against pathogen invasion, and also to neutralize toxins and viruses.

Our previous studies extended this classic view by finding a role for IgA in the maintenance of commensal gut microbiota.

By using genetically modified mice, we showed that IgA-deficiency caused the expansion of certain members of commensal bacteria in the gut.

Thus, IgA is functioning not only to protect us from harmful pathogens but also to maintain the commensal gut microbiota in mice and humans.

Why is it important to study how antibodies affect the microbiome?

Gut microbiota are essential for many aspects of our health, and a disturbed microbiome can cause many diseases such as obesity, autoimmune diseases and colitis.

Understanding the mechanisms behind the maintenance of a “healthy” microbiota in the gut may lead to the development of new methods for the treatment or prophylaxis of diseases.

Bacteria in the gut microbiomeImage Credit: Anatomy Inside / Shutterstock

Our body consumes a lot of energy to generate large amounts of gut IgA, but very little is known about how the IgA interacts with commensal microbiota to induce beneficial effects for the host.

This system is very complex, considering the heterogeneity of the IgA repertoire and also the diversity of the gut microbiota both in composition and metabolic function.

To understand the mechanisms involved in the maintenance of gut homeostasis, we need to dissect this complexity, and the study of the interaction between IgA and the microbiome plays a major role in this.

Please describe your recent research.

We recently proved that IgA antibodies promote the growth of beneficial bacteria in the gut of a mouse model.

Firstly, in order to eliminate IgA-heterogeneity, we developed monoclonal IgA that recognizes OVA protein (7-6IgA). We found that the 7-6IgA was heavily glycosylated and bound on the surfaces of many bacteria independent of the antigen recognition site of the antibody.

Among the bacteria strains we tested, Bacteroides thetaiotaomicron (B.theta) – a prominent human gut microbiota – had the highest capacity to bind on the glycosylated 7-6IgA.

We next developed a mouse system in which 7-6IgA was the only gut IgA, and concomitantly colonized it with B. theta.

In the cecum of these mice, the gene expression profile of B. theta was significantly altered including the up-regulation of a functionally uncharacterized operon. We provisionally named this operon Mucus-Associated Functional Factor (MAFF).

Interestingly,  MAFF expression in vivo was induced only under the presence of diverse microbiota but not in mono-colonized mice, indicating that the function of this operon requires interaction with other bacterial members.

We observed that symbiotic bacteria belonging to phylum Firmicutes expanded under the function of the MAFF system and in the presence of IgA, showing that IgA and the MAFF system plays a critical role in symbiotic interactions between these bacterial members.

Finally, we applied chemically induced colitis to the B. theta colonized mice. Surprisingly, we found that the mice colonized with the MAFF-deletion mutant of B. theta quickly died from severe colitis, but those mice colonized with wild-type B. theta were protected from the colitis.

This was due to the metabolites produced by the expanded members of Firmicutes, which enhanced the regeneration of damaged epithelial cells. These studies showed that heavily glycosylated IgA induced the MAFF genes that promote symbiosis via inter-phylum interactions and maintain colonic homeostasis.

What impact could this research have on humans with conditions such as inflammatory bowel disease (IBS)?

In our experiments, we treated mice with antibiotics to colonize B. theta. We observed that there were clear batch effects among the experiments for chemical-sensitive and chemical-resistant groups after the antibiotics treatment.

Image Credit: Kateryna Kon / Shutterstock

The efficient elimination of the members of Firmicutes by antibiotics enhanced the severity of the colitis, and the effect of the MAFF system was clearly observed in chemical-sensitive batches of the experiments.

I think there would be heterogeneity between our research and ulcerative colitis patients. If so, we could categorize patients into subgroups according to the composition of their gut microbiome.

The IgA-MAFF axis could be an interesting target for IBD studies in some subgroups of ulcerative colitis patients because the MAFF system is present in human colonic mucus.

We are not yet ready for human studies, but I am hopeful that our research might have an impact on IBD studies and help in the development of new treatments and/or prophylaxis for ulcerative colitis.

What are the next steps for your research?

The next step is to identify the molecular target of the MAFF system and find out how its expression is regulated along with neighboring genetic elements.

We would also like to identify and isolate the members of Firmicutes who strongly interact with B. theta via the MAFF system, would be a powerful driving force to expand our current knowledge.

It would also be interesting to tackle more details of the heterogeneity of glycosylation status of gut IgA in mice and humans. We believe that answering these questions will help us to understand the detailed mechanisms of how gut microbiota maintain equilibrium in our body.

Where can readers find more information?

About Dr. Keiichiro Suzuki

Dr. Suzuki started his career in 1996 as a clinician in a department of gastroenterology, internal medicine.

After 5 years training as a gastroenterologist, he started his scientific career as a PhD student in the laboratory of Professor Tasuku Honjo, at Kyoto University. It was in Honjo’s lab that he met Sidonia Fagarasan, who had already published many interesting papers about IgA and mucosal immunity.

Dr. Suzuki obtained a Ph.D. of medicine at Kyoto University in 2004, and soon joined Sidonia’s lab at RIKEN Yokohama Institute as a postdoctoral fellow.

His next move was to the Innovation Center for Immunoregulation Technologies and Drugs, AK project, in Kyoto University as an Associate Professor, in 2011.

In 2016, he re-joined Sidonia’s lab in the RIKEN Yokohama Institute as a senior scientist.

Tagged with:

About author

Related Articles