Longitudinal PRIMM Data published in Nature Medicine

Longitudinal PRIMM Data published in Nature Medicine

 

The first longitudinal assessment of metagenomic signatures along the ICI/cancer treatment journey has been published by our grantees in Nature Medicine. The publication entitled “Longitudinal gut microbiome changes in immune checkpoint blockade in advanced melanoma” expands our understanding on how the microbiome may impact response to cancer treatment.

Notably, the study introduces “balance scores” – a collection of bacteria that play crucial roles in both positive and negative associations with treatment response, not just at the beginning but throughout the treatment process.

🔍 So, why is this important?

  • It highlights the necessity of longitudinal sampling, suggesting that a single baseline gut microbiome sample might not capture  how bacteria influence the immune system and treatment response over time.
  • The published balance score, comprising approximately 9 key bacteria, holds potential for translation into diagnostic tools and therapeutic interventions.
  • As a next step the team is analyzing multi-omic data, especially adding a metabolomic layer, promising to further enhance our ability to predict treatment outcomes by understanding microbial function.

Huge congratulations to this impactful collaborations among Johannes Björk, Laura Bolte, Geke Hospers, Rinse Weersma from UMCG; Karla Lee, Veronique Bataille and Tim Spector from KCL and Lisa Derosa, Laurence Zitvogel (IGR), Nicola Segata (University of Turin) and many more.

Please find the full open-access publication here: https://www.nature.com/articles/s41591-024-02803-3

This publication adds to a series of publications from the same cohort, find them here:

Overall, this is paving the way for more personalized and effective cancer treatments.


Continue Reading

Related Articles

More effective cancer immunotherapy thanks to the gut microbiome

More effective cancer immunotherapy thanks to the gut microbiome

For more than four years, Seerave Foundation has been supporting the outstanding research teams at King’s College London (UK), UMCG (NL) and University of Trento (I) to find out whether there is a link between the presence and function of the gut microbiome and the outcome of cancer immunotherapy. We are thrilled to see this milestone work being published in Nature Medicine!

Congrats to all the authors and especially Karla Lee, Andrew Thomas, Laura Bolte, Johannes Björk, Laurence Zitvogel, Veronique Bataille, Geke Hospers, Tim Spector, Rinse Weersma and Nicola Segata from the Seerave network!

In summary, the team found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A panel of species, including Bifidobacterium pseudocatenulatumRoseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and non-responders.

We hope that this open access publication will drive more research into finding the mechanistic answers needed to drive personalised microbiome-targeted interventions forward. Dedicated papers regarding the association of different diet patterns with response in the same cohorts will be published separately in the coming months (as well as papers including proteomic, glycomic and metabolomic analysis).

Stay tuned!

Source: https://www.nature.com/articles/s41591-022-01695-5.pdf


Continue Reading

Related Articles

The Microbiota Vault is being launched in Switzerland

The Microbiota Vault is being launched in Switzerland

In 2018, Seerave embarked on the vision of Martin Blaser and Gloria-Maria Dominguez-Bello aiming to establish “The Microbiota Vault” – an initiative examining the potential of setting up a global repository of human microbiota. This repository, a “Noah’s Ark for microbes” would focus on the preservation of the current global diversity of the human microbiota, on backing-up global research collections and to further explore the role of the microbiome in health and disease. The launch of this important project was only possible thanks to philanthropic co-impact including Gebert Rüf Foundation and Rockefeller Foundation joining forces.

We hope others will join in as well!

For our German-speaking network: please have a look at the recent NZZ article for more in depth reporting.


Continue Reading

Related Articles

The gut microbiome: what the oncologist ought to know

The gut microbiome: what the oncologist ought to know

The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and protection against pathogens.

Strong evidence is emerging to support the effects of the GM on the development of some malignancies but also on responses to cancer therapies, most notably, immune checkpoint inhibition.

Tools for manipulating the GM including dietary modification, probiotics and faecal microbiota transfer (FMT) are in development. Current understandings of the many complex interrelationships between the GM, cancer, the immune system, nutrition and medication are ultimately based on a combination of short‐term clinical trials and observational studies, paired with an ever-evolving understanding of cancer biology.

The next generation of personalised cancer therapies focusses on molecular and phenotypic heterogeneity, tumour evolution and immune status; it is distinctly possible that the GM will become an increasingly central focus amongst them.

The aim of this review is to provide clinicians with an overview of microbiome science and our current understanding of the role the GM plays in cancer.

Source: https://www.nature.com/articles/s41416-021-01467-x


Continue Reading

Related Articles

Happy #WorldMicrobiomeDay 2021! 🎉

Happy #WorldMicrobiomeDay 2021! 🎉

On World Microbiome Day we celebrate all things microbial, all around the world.

Today we would like to raise special attention to one of our initiatives: The collaboration between MyFoodRepo @EPFL and Microsetta @UCSD. Together they aim to roll out a US-wide citizen science project aiming to collect as much information as possible on everyday food items we consume. This information will help to train an algorithm that enables researchers in the future to better track nutrition and give more profound insights. Therefore…

We ask all of you to contribute to the microbe revolution: the “FoodRepo Scan” app is a new way #CitizenScientists can help advance the understanding between diet & microbes! Download the app on iOS or Android and start adding barcodes and images of food items you have at home or encounter in any store. The data will then become publicly available on FoodRepo. This will create a hugely valuable dataset, available to anyone in the world, with which research into nutrition and health will be accelerated. For example, it will serve as a nutritional library for the MyFoodRepo platform, a new AI-assisted tool that allows tracking of high dimensional nutritional data during clinical studies. Become part of tomorrow’s science today!

The collaboration between Microsetta and the Digital Epidemiology team at EPFL is made possible thanks to the support from the Seerave Foundation for nutrition and microbiome research @Seerave Foundation; please see http://www.seerave.org/projects for more details.


Continue Reading

Related Articles

Long-term dietary patterns are associated with pro- inflammatory and anti-inflammatory features of the gut microbiome

Long-term dietary patterns are associated with pro- inflammatory and anti-inflammatory features of the gut microbiome

Researchers found that specific foods and nutrients correlated with species known to have mucosal protection and anti-inflammatory effects, according to data published in Gut.

“We identified dietary patterns that consistently correlate with groups of bacteria with shared functional roles in both health and disease,” Laura A. Bolte, BSc, from the department of gastroenterology and hepatology, University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands, and colleagues wrote. “Moreover, specific foods and nutrients were associated with species known to infer mucosal protection and anti-inflammatory effects. We propose microbial mechanisms through which the diet affects inflammatory responses in the gut as a rationale for future intervention studies.”

Bolte and colleagues analyzed the relationship between 173 dietary factors and the microbiome of 1,425 patients from different cohorts including Crohn’s disease, ulcerative colitis, irritable bowel syndrome and the general population. They profiled gut microbial composition and function with shotgun metagenomic sequencing assessed dietary intake via food frequency questionnaires.

“We performed unsupervised clustering to identify dietary patterns and microbial clusters,” Bolte and colleagues wrote. “Associations between diet and microbial features were explored per cohort, followed by a meta-analysis and heterogeneity estimation.”

The researchers identified 38 links between dietary patterns and microbial clusters. In their meta-analysis of healthy individuals and patients with IBS, Crohn’s disease and UC, investigators found 61 individual foods and nutrients correlated with 61 species and 249 metabolic pathways.

“Processed foods and animal-derived foods were consistently associated with higher abundances of Firmicutes, Ruminococcus species of the Blautia genus and endotoxin synthesis pathways,” Bolte and colleagues wrote. “The opposite was found for plant foods and fish, which were positively associated with short-chain fatty acid-producing commensals and pathways of nutrient metabolism.”

DOI: doi:10.1136/gutjnl-2020-322670.

Story Source:  https://www.healio.com/news/gastroenterology/20210405/diet-patterns-linked-with-gut-proinflammatory-antiinflammatory-features


Continue Reading

Related Articles

Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

Limited experimental evidence bridges nutrition and cancer immunosurveillance. Here, the team at IGR Paris shows that ketogenic diet (KD) or its principal ketone body, 3-hydroxybutyrate (3HB), most specifically in an intermittent scheduling, induced T cell-dependent tumour growth retardation of aggressive tumour models.

In conditions in which anti-PD-1, alone or in combination with anti-CTLA-4, failed to reduce tumour growth in mice receiving a standard diet, KD or oral supplementation of 3HB reestablished therapeutic responses. Supplementation of KD with sucrose (which breaks ketogenesis, abolishing 3HB production) or with a pharmacological antagonist of the 3HB receptor GPR109A abolished the anti-tumour effects. Mechanistically, 3HB prevented the ICB-linked up-regulation of PD-L1 on myeloid cells while favouring the expansion of CXCR3+ T cells. KD induced compositional changes of the gut microbiota with distinct species such as Eisenbergiella massiliensis commonly emerging in mice and humans subjected to carbohydrate low diet interventions and highly correlating with serum concentrations of 3HB. Altogether, these results demonstrate that KD induces a 3HB-mediated antineoplastic effect that relies on T-cell mediated cancer immunosurveillance.

Source: http://www.ncbi.nlm.nih.gov/pubmed/33320838

Continue Reading

Related Articles

Landmark nutritional study PREDICT shows dietary inflammation after meals varies dramatically among healthy adults

Landmark nutritional study PREDICT shows dietary inflammation after meals varies dramatically among healthy adults

Researchers led by the Department of Twin Research announced today the first published results from PREDICT, the largest ongoing nutritional study of its kind.

The team found a wide range of metabolic responses after eating in apparently healthy adults, and that inflammation triggered by the food we eat varies up to ten-fold.

Poor metabolic responses to food, where the body takes longer and works harder to clear the blood of fat and sugar, are linked with increased risk of conditions such as low-grade inflammatory diseases including heart disease, type 2 diabetes and obesity.

The results suggests improved health could be achieved by eating foods that are personalised to reduce inflammation after meals.

Senior researcher on the study Professor Tim Spector said:   “When it comes to weight, we’ve traditionally put a huge emphasis on factors we have no control over, like genetics. The fact is, while genetics plays a role, there are many more important factors that impact an individual’s response to food and maintenance of a healthy metabolism. This study shows that achieving a healthy weight requires a scientific approach to eating that takes into account an individual’s unique biology.

Led by Professor Tim Spector and his team at King’s College London and spin-out  health science company ZOE, the PREDICT study consisted of 1,103 participants, including 660 identical and non-identical twins from TwinsUK.

The study measured a wide range of markers from blood glucose, fat and insulin levels to exercise, sleep and gut bacteria (microbiome) over two weeks. It is the most detailed study to date to look at all the different factors that affect our responses to food together.

Despite wide variation in metabolic responses between participants, results from identical meals eaten on different days showed that individual responses to the same foods were remarkably consistent for each person.

The team also found that the optimal time to eat for nutritional health also depends on the individual rather than fixed “perfect” mealtimes. The researchers found that some people clearly metabolised food better at breakfast while others saw no difference.

Dr Sarah Berry, Senior Lecturer of Nutrition Sciences at King’s College London, led on the inflammation part of the study. She said:  “We found that the increase in fat and glucose in our blood after eating a meal initiates an inflammatory response which differs hugely between individuals. Dietary and lifestyle strategies to reduce prolonged elevations in blood fat and glucose may therefore be a useful target to reduce low-grade inflammation, and protect people from low-grade inflammatory conditions such as type 2 diabetes and cardiovascular disease.

Story Source: https://twinsuk.ac.uk/landmark-nutritional-study-predict-shows-dietary-inflammation-after-meals-varies-dramatically-among-healthy-adults/

DOI: https://doi.org/10.1038/s41591-020-0934-0


Continue Reading

Related Articles

Switzerland potential home for “Noah’s Ark” of microbes to preserve human health in perpetuity

Switzerland potential home for “Noah’s Ark” of microbes to preserve human health in perpetuity

A new study supported by Seerave Foundation and led by world-leading scientists finds that the creation of a “microbial Noah’s Ark” is feasible and should move forward into a pilot project phase with Switzerland one of two locations. The ultimate aim is to preserve the trillions of microbes that are essential to human health.

The Microbiota Vault would gather beneficial germs from human populations whose microbiomes are uncompromised by antibiotics, processed diets and other ill effects of modern society that have contributed to massive loss of microbial diversity and an accompanying rise in health problems. The human microbiome includes the trillions of microscopic organisms that live on and in our bodies, contributing to our health in myriad ways.

The feasibility study was prepared by two independent Swiss firms (EvalueScience and advocacy) and supported by non-profit institutions and universities active in the field of the human gut microbiome. The funding consortia includes the Swiss Gebert Rüf Foundation along with the Seerave Foundation, the Calouste Gulbenkian Foundation (Portugal), Rutgers University (USA), Kiel University (Germany), Canadian Institute for Advanced Research (Canada), Bengt E. Gustafsson symposium foundation (affiliated to Karolinska Institutet, Sweden) and UC San Diego School of Medicine (USA).

Dr. Manuel Fankhauser, Chief Scientific Officer of Seerave Foundation and member of the project team, commented: “We are very excited to have established a solid base for this ambitious global project. As a next step, a 2-year pilot phase will test the logistical and legal framework. Apart from around CHF 1 million of funding, this will require us to pool resources and networks across the globe. We have already visited multiple Swiss army bunkers that could be repurposed for the Microbiota Vault in phase 2. We hope to move forward as quickly as possible, before even more microbial diversity will be lost.”

“Populations in modern societies have lost much of their microbiome because of the damage caused by overuse of antibiotics and other medicines, over-reliance on high fat, processed foods, and other factors of industrialization,” said Blaser. “The Microbiota Vault initiative will help us work with indigenous cultures, in whom the microbiome is more intact, to find microbes that could be stored, replicated, and reintroduced to protect the health of all people. When new pathogens arise, such as SARS-CoV-2, harnessing the good microbes to fight the bad is one potential approach.”

The researchers hope it may be possible one day to prevent disease by reintroducing lost microbes. But that could happen only if researchers first collect beneficial microbes, e. g. from remote Latin American and African populations that have the greatest microbiota diversity before they, too, experience the effects of urbanization. People living in urbanized societies have lost a substantial part of their microbiota diversity; the gut flora of most Europeans and Americans, for example, is half as diverse as that of hunter-gatherers in isolated Amazonian villages. Importantly, the characterization of samples stored in the Microbiota Vault would be available in a transparent and open access fashion, enabling researchers across the globe and optimizing use of information and use of the specimens in the local collections.

About The Microbiota Vault
The Microbiota Vault aims to conserve the diverse human microbiota to ensure long-term health for humanity. It will do this by establishing a non-profit non-governmental organization, bringing scientists and policy makers together to ensure consensus, creating a global repository of coevolved human microbes, connecting existing regional collections and promoting regional capacity building.

The feasibility study will be available for download to the public via www.microbiotavault.org as of June 11th, 18.00 pm CET.

 


Continue Reading

Related Articles

Stanford’s smart toilet analyzes urine and feces for signs of disease

Stanford’s smart toilet analyzes urine and feces for signs of disease

The toilets of the future will scan and analyze human waste in detail for faster detection of various diseases.

Human urine and feces contain a lot of information about human health and wellbeing, and therefore scientists and engineers are developing new technologies that could help us unlock it. Among them is a group of scientists from Stanford University, which is developing new disease-detecting technology in the lab.

They recently introduced a new type of “smart toilet” fitted with the technology that automatically scans urine and faeces for possible signs of disease. The intelligent toilet system can detect different types of cancer, such as colorectal or urologic cancers, as well as some digestive and kidney disorders.

When I’d bring it up, people would sort of laugh because it seemed like an interesting idea, but also a bit odd,” said Gambhir, professor, and chair of radiology. With a pilot study of 21 participants now completed, Gambhir and his team have made their vision of a precision health-focused smart toilet a reality.

The advantage of this toilet system is that it can be installed relatively easily on an existing toilet and adapts to the inside of the bowl. The attachment is packed with various sensors and cameras that capture video of urine and feces, which is then processed by a set of algorithms that can distinguish normal “urodynamics” (flow rate, stream time and total volume, among other parameters) and stool consistencies from those that are unhealthy.

Of course, the device also monitors biological characteristics such as white blood cell counts and levels of certain important proteins that are indicative of a variety of diseases.

To differentiate the plurality of people who will probably use the smart toilet, the system is equipped with a fingerprint scanner on the flush lever. However, the Gambhir team realized that there might be scenarios in which one person uses the toilet, but another flush it or the toilet drains automatically after use. To solve this problem, the team added a small scanner that images a rather camera-shy part of the body.

We know it seems weird, but as it turns out, your anal print is unique,” said Sanjiv “Sam” Gambhir, professor and chair of radiology. The scans – both finger and nonfinger – are used purely as a recognition system to match users to their specific data. No one, not you or your doctor, will see the scans.

To test its concept, the team carried out a pilot study involving 21 participants. For several months, all of them used the toilets, which enabled scientists to establish personalized health checks. Gambhir hopes to test it with more adherents as they continue to make improvements, such as a real biochemical analysis of stool.

Gambhir’s other goal is to further develop a molecular analysis for stool samples. “That’s a bit trickier, but we’re working toward it,” Gambhir said. “The smart toilet is the perfect way to harness a source of data that is typically ignored – and the user doesn’t have to do anything differently.”

Story Source: https://www.techexplorist.com/stanford-smart-toilet-analyzes-urine-poop-signs-disease/31501/

DOI: https://doi.org/10.1038/s41551-020-0534-9


Continue Reading

Related Articles