The interplay between diet, the microbiota and immunity

Research in mice shows how diet alters immune system function through a gut microbe

At a glance:

  • Research in mice demonstrates how diet alters a gut microbe molecule that in turn prompts immune cells to downregulate inflammation
  • Study illustrates the molecular mechanism behind the longstanding view that diet, microbiota and immunity influence each other in myriad ways
  • Following more testing, findings could inform the design of small-molecule drugs that regulate immune response to treat inflammatory conditions

An international team of researchers including Monash University have found molecular proof of how diet ultimately affects immunity through the gut microbiome.

The team’s work, conducted in mice, have pinpointed a microbial molecule called B. fragilis that sets off an immune-signalling cascade triggered by the host’s diet of a metabolic breakdown of branch-chained amino acids in the mouse gut.

The multistep pathway begins with B. fragilis taking up the branch-chained amino acids and then converting them by a specific enzyme into sugar-lipid molecules that also have branched chains that are then spotted and picked up by a class of immune-signalling cells known as antigen-presenting cells, which in turn induce natural killer T (NKT) cells to exercise their immunoregulatory response through upregulating inflammation-controlling genes and immune-regulatory chemicals.

Furthermore, the team found that B. fragilis alters the structure of the sugar-lipid molecules that it metabolizes and renders them better capable of binding to receptors on specific immune cells and initiating a signalling cascade that culminates in downregulating inflammation.

The findings, published November 10 in Nature, offer a unifying explanation for the complex interplay between diet, gut microbiota and immune function. They are the result of collaboration among scientists at Harvard Medical School, Brigham and Women’s Hospital, Seoul National University, and Monash University in Australia.

NKT cells line the human gastrointestinal tract, the lungs and are also found in the liver and spleen and likely play a significant role in immune regulation and are implicated in a range of inflammatory conditions including ulcerative colitis, and to a possible role in airway inflammatory conditions, such as asthma.

While scientists have surmised for a long time that diet plays a role in immune health, the new study elucidates the precise molecular cascade behind diet and immune health, said study senior author Dennis Kasper, professor of immunology at Harvard Medical School.

“We have shown how diet affects the immune system through a microbe mediator in the gut, and this is a really striking example of the diet-microbiota-immunity triad at play,” Kasper said. “What this work really does is provide a step-by-step pathway from beginning to end that explains how and why this triad works and how diet ultimately affects the immune system.”

Using a structural biology approach, Professor Jamie Rossjohn, ARC Laureate Fellow at the Monash Biomedicine Discovery Institute, elucidated how the lipid structure engages with and binds to antigen-presenting cells—the immune cells that give NKT cells the go-ahead to produce anti-inflammatory chemicals.

“This work offers a great example of trans-disciplinary discovery-based research aimed at answering a major question in biomedical sciences, namely how the immune system can be modulated by the interplay between diet and the microbiota,” Professor Rossjohn said.

Study coinvestigator Seung Bum Park, professor of chemistry at Seoul National University, synthesized and the Harvard team tested 23 different configurations of the microbe-made immunomodulatory molecule to determine how each one interacts with the immune cells that regulate inflammation.

“Our new work demonstrates that the branching of the lipid structure induces a very different response—the branching in the structure induces an anti-inflammatory rather than a proinflammatory response,” Professor Kasper said.

The findings offer the hope that inflammatory diseases mediated by these NKT cells could one day be treated with inflammation-dampening microbial molecules made in the lab, the researchers said.

Co-authors included Sungwhan F. Oh, T. Praveena, Heebum Song, Ji-Sun Yoo, Da-Jung Jung, Deniz Erturk-Hasdemir1, Yoon Soo Hwang, ChangWon Lee, Jérôme Le Nours, Hyunsoo Kim, Jesang Lee, and Richard Blumberg.

Read the full paper (view only)  via SharedIt in Nature titled: Host immunomodulatory lipids created by symbionts from dietary amino acids. 

Original article

Congrats Jamie: Highly Cited researcher again!

Congratulations to Jamie who is again on the Highly Cited Researchers 2021 list of the world’s most Highly Cited Scientists, which is published annually by Clarivate Analytics.

From Clarivate: Recognising the true pioneers in their fields over the last decade, demonstrated by the production of multiple highly-cited papers that rank in the top 1% by citations for field and year in the Web of Science™. Of the world’s scientists and social scientists, Highly Cited Researchers truly are one in 1,000.

Original article

BDI researchers honoured in annual Dean’s Awards

Congratulations to Drs Adam Shahine and Milda Kaniusaite, who have each been recognised with a Dean’s Award for Excellence in 2021 for research carried out at the Monash Biomedicine Discovery Institute (BDI).

Dr Shahine won an award in the Excellence in Research – Early Career Researcher category.

“It was an honour to receive the ECR category for the Dean’s Excellence in Research award,” he said.

Dr Shahine has researched the immune system and its functions regulating and dysregulating immunity in our bodies since 2014 in Professor Jamie Rossjohn’s lab. “This work has provided a number of novel molecular insights into how presentation of lipid antigens plays a role in modulating adaptive immunity,” he said.

The research has been appeared in a number of high quality publications such as ‘Nature Cancer’ and ‘Science Immunology’, and been presented at conferences at places including the UK and US. “And that has all made an impact on the field,” Dr Shahine said. “Building upon this body of work, I was awarded an ARC DECRA Fellowship to continue research in this field to explore uncharted territory.”

Dr Shahine acknowledged the role of Professor Rossjohn in his career successes. “I definitely wouldn’t be where I am today without the mentorship of my supervisor Jamie Rossjohn, the supportive network within the laboratory, as well as collaborators at Harvard,” he said. The Australian Synchrotron has been invaluable, he added.

Dr Shahine is supervising three junior post-doc researchers and three PhD students, as well as conducting his own research.

Biochemist Dr Milda Kaniusaite’s research in the field of discovering new antibiotics earned her a Dean’s Award for Doctoral Thesis Excellence.

She said the exciting interdisciplinary project sought to understand the biosynthesis mechanism of clinically relevant antibiotics such as Teicoplanin and Vancomycin, then, based on these findings, re-engineer the biosynthesis pathway and demonstrate production of altered sequence products.

“This project was highly unique, given the fact that I was able to isolate whole antibiotic biosynthesis mega-enzymatic machinery from bacteria,” Dr Kaniusaite said. “In general, findings from my PhD can be considered as a set of rules that provide novel guidelines for effective biosynthetic pathway re-engineering leading to the synthesis of new molecules,” she said.

“The results from this study appear to be universal and can be relevant to the re-engineering of many other clinically important compounds produced by mega-enzymes. “This I believe will be of great importance in developing new drugs related to the treatment of antibiotic-resistant bacterias,” she said.

Dr Kanuisaite said it was a great pleasure and honour to win the award. “The award motivates and boosts my confidence that I am on the right track being a researcher and working for science. It helps me to open new doors, get new opportunities and gives an additional strength dealing with new and upcoming challenges.”

She is now a post-doctoral researcher at the Institute for Clinical Medicine at the University of Oslo, Norway.

The awards were given to 25 Monash Medicine, Nursing and Health Sciences individuals and team recipients for outstanding achievements in education, research, industry education programs, professional services, and doctoral thesis.

During the virtual event this month, Professor Christina Mitchell AO, Dean of Monash Medicine, Nursing and Health Sciences acknowledged the efforts of all staff and PhD graduates. “I would like to congratulate all of our award winners. You are an amazing group and outstanding in every way. I look forward to congratulating you in person soon,” she said.

Videos of this year’s winners discussing their projects and achievements can be viewed on the Dean’s Award for Excellence website.

About the Monash Biomedicine Discovery Institute at Monash University

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.

Original article


Congrats Adam on The Dean’s Awards for Excellence in Research – Early Career Researcher in 2021

A message from the Dean

Monash Medicine, Nursing and Health Sciences is pioneering innovations, treatments and therapies that improve human health. We are a leading provider of healthcare education in Australia, and are passionate about building the medical workforce of the future globally.

We are proud of our staff and PhD students who are at the forefront of innovation and ground-breaking research and teaching.

Their goal is not only to educate and train the next generation of world-class health professionals, but also to inspire them to become leaders that educate and mentor others in their professorial fields.

The annual Excellence Awards is an opportunity to recognise and celebrate the achievements of our staff and some of our best and brightest students for their outstanding performance this year. All our recipients are working towards our shared vision of improving the human condition.

Congratulations to all the award winners. I applaud your dedication and hard work, and I encourage you to keep asking questions in your quest for better health outcomes.

I also know that for many of you, your achievements are underpinned by the strong support from family, friends and colleagues.

While we may not know what lies ahead, we do know that your hard work and dedication will have prepared you for whatever the future will hold.

The Dean’s Awards for Excellence in Research are awarded across six categories:

  • Excellence in Research – Economic and Social Impact
  • Excellence in Research – Economic and Social Impact (team)
  • Excellence in Research – Postgraduate Research Supervision
  • Excellence in Research – Early Career Researcher: Dr Adam Shahine – Watch Adam’s video interview below.
  • Excellence in Research – Enterprise
  • Excellence in Research – Enterprise (team)


Original article

Uncovering how T cells recognise the SARS-CoV-2 virus spike protein

The immune system is vitally important for resolving COVID-19 when individuals are infected with the SARS-CoV-2 virus. Moreover, the vaccines that are being administered to millions of people across the globe are designed to ‘pre-warn and arm’ the immune system so that if infected with SARS-CoV-2, individuals are significantly less likely to develop severe disease or die.  Here, two crucial arms of the immune system, namely B cells and T cells, play a central role.

While we have a molecular understanding of how antibodies, which are produced by B cells, can bind and neutralise the spike protein from SARS-CoV-2, up until now researchers did not know how T cell receptors (TCRs), which are found on T cells, recognise antigens that arise from the spike protein.

“T cells play an important role in immunity against both SARS-CoV-2 vaccination and severe acute respiratory infection. Although T cells in COVID-19 have been studied previously, the molecular basis underpinning TCR recognition of SARS-CoV-2 remained unknown. It has been a pleasure working with the Monash University team to conduct this extremely important work to understand how T cells recognise an antigen from SARS-CoV-2,” said University of Melbourne Professor Katherine Kedzierska, a laboratory head at the Peter Doherty Institute for Infection and Immunity.

In a world first finding, co-led by Monash University’s Dr Priyanka ChaurasiaDr Jan Petersen and Professor Jamie Rossjohn, and Professor Kedzierska, the team analysed the TCR recognition of a spike protein fragment when presented by an immune molecule, termed Human Leukocyte Antigen A2 (HLA-A2). This work, which utilised the Australian Synchrotron, was published in the Journal of Biological Chemistry. 

“This is a piece of a larger puzzle. While SARS-CoV-2 continues to evolve, we have to build our understanding of how effective immune responses work,” said Dr Jan Petersen.

The team provided important molecular insight into understanding how T cells of the human immune system respond to SARS-CoV-2. Different individuals mount differing immune responses to SARS-CoV-2, and this work provided fundamental insight into such an immune response.

Read the publication in the Journal of Biological Chemistry titled Structural basis of biased T cell receptor recognition of an immunodominant HLA-A2 epitope of the SARS-CoV-2 spike protein

[Paper: J Biol Chem. 2021 Aug 10;297(3):101065. doi: 10.1016/j.jbc.2021.101065.]

Original article

Also featured in ANSTO article: Understanding how adaptive immune cells recognise and interact with the SARS CoV-2 virus