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24 November 2025

How Fasting-Driven Microbiota Changes May Protect the Brain in Obesity: A Fascinating Conversation With Dr. Virginia Mela


Ask the author session

Understanding how our gut influences our brain is one of the most exciting frontiers in metabolic and liver-related research. For people living with MASLD/MASH (formerly NAFLD/NASH), obesity, and metabolic dysfunction, new insights into the gut–brain–liver axis are emerging every year.

One particularly compelling example is the recent paper published in GUT by Dr. Virginia Mela and colleagues: “Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis.”

In our latest Ask the Author session, Prof. Jean-François Dufour sat down with Dr. Mela to explore the study’s design, findings, and what they could mean for individuals at risk of fatty liver disease. The conversation is rich, accessible, and highly relevant for anyone interested in the interplay between nutrition, inflammation, cognition, and metabolic liver disease.

👉 You can watch the full interview on our website—don’t miss it.


A Closer Look: Three Diets, One Key Question

Dr. Mela and her team conducted a randomized controlled trial involving 96 participants with obesity. Participants were assigned to one of three well-defined dietary interventions for three months:

  • Mediterranean diet (rich in olive oil, fish, legumes, vegetables)
  • Ketogenic diet (very low carbohydrate, high fat)
  • Alternate-day fasting (restricted intake on fasting days; controlled intake on non-fasting days)

The goals?

  1. To determine how these diets affect weight loss
  2. To explore whether they can improve cognitive performance, given the well-established link between obesity and cognitive decline

All participants underwent detailed metabolic, inflammatory, microbiota, and cognitive assessments before and after the intervention period.


What They Discovered: Alternate-Day Fasting Stands Out

While all three diets produced similar weight loss—and the ketogenic diet led to the greatest reduction in fat mass—the alternate-day fasting diet had the most impressive effect on cognitive improvement.

Dr. Mela explains that this benefit appears to be driven by several biological changes:

1. Reduced systemic inflammation

Inflammatory markers fell significantly after the alternate-day fasting intervention, suggesting a broad anti-inflammatory effect.

2. Improved microglial function

Microglia—the brain’s resident immune cells—showed healthier, more functional behavior after exposure to participants’ post-diet biological samples.

3. Favorable shifts in gut microbiota

Alternate-day fasting increased specific beneficial bacterial taxa that correlated with cognitive improvements.

4. Increased riboflavin production

A standout finding was the rise in riboflavin, a microbiota-derived metabolite known for anti-inflammatory and immunomodulatory effects—potentially linking gut changes to brain improvements.

Prof. Dufour highlighted how elegant and multidimensional the study is, bridging microbiota composition, metabolites, brain immune cell activity, and cognition.


What Does This Mean for MASLD/MASH?

With new drugs entering the MASLD/MASH treatment landscape, lifestyle strategies remain essential. Dr. Mela emphasizes that dietary interventions like alternate-day fasting may play a powerful preventive role:

They help minimize metabolic dysfunction and inflammation—two key drivers of fatty liver disease progression. While diet alone may be insufficient in later disease stages, integrating such patterns early could reduce risk, support metabolic health, and potentially complement future pharmacotherapies.


Why You Should Watch the Full Interview

This conversation is not just about nutrition—it’s about how strategic dietary patterns reshape the microbiota, influence immune function in the brain, and potentially protect metabolic health.

Whether you’re:

  • living with MASLD/MASH,
  • a clinician advising patients,
  • a researcher in the metabolic field, or
  • simply someone curious about the gut–brain axis,

this interview offers science-based insights delivered in a clear and engaging way.

👉 Watch the full interview with Dr. Virginia Mela now here on the Swiss NASH Foundation website.
It’s an inspiring look at how dietary science continues to evolve—and how it may help us prevent and better understand metabolic liver disease.

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18 February 2025

Decoding MASLD: Uncovering Distinct Metabolic Subtypes for Targeted Treatment

In a recent “Ask the Author” session, Professor Stefano Romeo discussed his groundbreaking work on data-driven cluster analysis to identify distinct types of metabolic dysfunction associated with steatotic liver disease. The conversation highlighted a significant shift from “non-alcoholic” to “metabolic” in defining liver diseases, emphasizing a positive and more inclusive approach. This blog post delves into the key insights from the session, exploring the study’s design, findings, and implications for managing patients with Metabolic dysfunction-associated steatotic liver disease (MASLD).

Prof. Stefano Romeo answering to the questions of Prof. Jean-François Dufour.



Study Design and Methodology Professor Romeo’s study aimed to address the heterogeneity observed in Metabolic dysfunction-associated steatotic liver disease (MASLD). The research began with a simple clustering approach using six readily available clinical variables: HbA1c, triglycerides, LDL, age, BMI, and ALT . This unsupervised machine learning method identified three distinct clusters, two of which showed histological evidence of Metabolic dysfunction-associated steatotic liver disease (MASLD) .

Key Findings The study revealed significant differences between the identified clusters:

  • Cluster 1: Characterized by higher triglycerides and HbA1c levels, indicating more pronounced dyslipidemia and diabetes .
  • Cluster 2: Showed increased ALT levels, suggesting a more liver-specific disease .
  • UK Biobank Replication: The findings were replicated in the UK Biobank, confirming that the cluster with higher triglycerides and HbA1c was associated with more cardiovascular events, while the cluster with elevated ALT was primarily linked to liver-related events .

Causality between Liver Disease and Cardiovascular Events Further research explored the causal relationship between Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular events using polygenic risk scores based on genes affecting fatty liver disease: TM6SF2 and PNPLA3 .

  • TM6SF2 and PNPLA3: Associated with lipoprotein retention, higher MASH and fibrosis, and lower cardiovascular disease risk .
  • Increased Lipogenesis: The group without lipoprotein retention showed an association with the entire spectrum of cardio-renal metabolic syndrome .

Two Distinct Phenotypes of MASLD The combined results from the cluster analysis and genetic studies suggest the existence of two distinct types of Metabolic dysfunction-associated steatotic liver disease (MASLD) :

  1. Liver-Specific MASLD: Primarily affects the liver due to liver-specific mechanisms .
  2. Systemic MASLD: Affects the entire body, with broader systemic implications .

Implications for Patient Management These findings have significant implications for how Metabolic dysfunction-associated steatotic liver disease (MASLD) patients are managed . Recognizing these distinct phenotypes allows for more targeted treatment strategies, addressing specific metabolic dysfunctions and reducing the risk of cardiovascular events in susceptible individuals .

Conclusion Professor Romeo’s work marks a significant advancement in understanding the complexities of Metabolic dysfunction-associated steatotic liver disease (MASLD). By identifying distinct metabolic subtypes and their associated risks, this research paves the way for more personalized and effective treatment approaches, ultimately improving patient outcomes .

Link to full article in Nature journal.

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10 June 2021

Max Meyer Young Talent in NASH Prize and Max Meyer Research Prize awarded!

Thanks to medical research we have tools against hepatitis B and hepatitis C. We can vaccinate to prevent infection with hepatitis B. We can control with medication chronic hepatitis B. We can cure patients affected with chronic hepatitis C. Now the most frequent  liver disease affecting millions is non-alcoholic steatohepatitis. Medical research still has to find treatment and biomarkers for this disease therefore this is with great pleasure and honor that we are giving prizes to investigators active in this field. The Max Meyer Young Talent in NASH Prize is going to a talented medical student Ms Pauline Fauroux working on biomarkers to better identify patients at risk to progress to cirrhosis. Ms Pauline Fauroux is working in Lyon and due to the pandemic situation is unable to come today to receive in person her prize.

The second prize, the Max Meyer Research Prize is going to Dr Yuly Mendoza for her publication on a simple combination of tests to select patients with advanced liver disease at risk of complications. Dr Mendoza got her MD degree in Colombia and is working for several years in Switzerland for her PhD. We congratulate both of you for your prize and wish you, in name of the Swiss NASH Foundation a lot of success for your future.

For regular update on new research follow our Twitter account: https://twitter.com/swissnash

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4 June 2021

International Nash Day

The International Nash Day organised by the Global Liver Institute (GLI) is coming up on the 10. June 2021 and we are happy to announce that we will take an active part in it!

The theme for the 2021 #NASHday is NASH Around the World!

Please join our global effort to raise awareness about nonalcoholic steatohepatitis (NASH), the advanced form of nonalcoholic fatty liver disease (NAFLD), and the actions that people can take to address this life-threatening disease worldwide. 

If you register for the event you can join different panels on topics like:

  • NASH as a Global Public Health Challenge
  • NASH and Liver Cancer
  • NASH and Obesity
  • Pediatric NASH
  • NASH and Diabetes
  • Beyond the Biopsy: Innovations in Diagnostics
  • NASH in Lean Individuals
  • NASH: A Conversation in the Black Community

Please follow the hashtag #NashDay on Twitter for updates about this event We do appreciate if you follow us @swissnash as well 😉

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7 April 2021

Call for submissions: Young Talent in NASH – Student prize of the Swiss NASH Foundation

Application for the Student prize of the Swiss NASH Foundation 

In 2021, the Swiss NASH Foundation will for the first time award the Young Talent in NASH prize to two exceptional students. Eligible are all students currently conducting or planning to conduct research activities in the field of non-alcoholic fatty liver disease within Switzerland or in collaboration with a Swiss group. Priority will be given to clinical, patient-centered research. 

The aim of the Student prize of the Swiss NASH Foundation is to further young talent in the field of non-alcoholic liver disease with a focus on developing skills to communicate scientific topics to an interdisciplinary and/or non-scientific audience (e.g. patients, caretakers). Participants are thus encouraged to elaborate on their plans regarding communication of their research topic and findings in their application. 

The prize of 1’500 CHF will be distributed equally among the winners. 

Requirements 

  • Bachelor or Master student at an institution of higher education. 
  • Research project in the field of non-alcoholic fatty liver disease at a Swiss institution or with a Swiss group. The research activity should be ongoing or start within six months of application. 
  • Accepted publications or manuscripts are not eligible for evaluation but may be eligible for the category Research prize of the Swiss NASH Foundation. 
  • Winners agree to participate in science communication coaching with members of the Swiss NASH social media team to develop three contributions for dissemination on the Swiss NASH social media channels. 

Selection of the winners 

The winners will be selected by an independent international panel of experts in the field of non-alcoholic liver disease. Experts will be announced after the submission of proposals. 

Required documents and submission 

  • Letter of motivation (max. 1 page) 
  • Project description (max. 2 pages) covering the following: Aim, Methods, Significance, Timeline of the project, Role of the applicant in the project incl. brief concept for communication of research and findings 
  • Curriculum Vitae 

Documents should be submitted in English as a single PDF-file by 15.05.2021 end of day (CET) to: info at swissnashfoundation dot org 

Aim of the Foundation 

The Swiss NASH Foundation was launched in October 2019 in Bern, Switzerland. The Swiss NASH Foundation is a non-profit organization committed to the dissemination of knowledge and raising of awareness about NASH. Through funding cutting edge research projects as well as increasing knowledge and awareness about NASH, the Foundation aims at contributing to treatment discovery as well as improving patients’ quality of life.