What initially sparked your interest in studying the human microbiome, and how did your academic journey in this field develop?
After completing my PhD in 2006, which focused on the pathophysiological mechanisms of chronic kidney disease, I felt the need to bridge my two areas of expertise: microbiology (from my undergraduate studies) and chronic kidney disease (from my PhD). At that time, the first studies using "innovative" high-throughput sequencing techniques were emerging, enabling the study of microbial communities as a whole rather than microorganism by microorganism. In subsequent years, these new technologies revolutionised - and continue to revolutionise - our understanding of the host-microorganism relationship, revealing a greater diversity in microbial communities and a crucial, complex role in human health. Naturally drawn by a desire to be part of this revolution, in 2014, I initiated a study aiming to characterise the oral and gut microbiome in chronic kidney disease. A cohort of patients was gathered with sample collection and clinical data compilation. Funding for high-throughput sequencing was only secured in 2018, so until then, evaluations were conducted using other microbiology techniques. Several other projects followed, always focused on the relationship between the microbiome and human health: OralBioBorn (initiated in 2019) and integrated into the Dutch Metahealth consortium (in 2022), which aims to understand how maternal pathology (obesity, hypertension, and gestational diabetes) may affect the acquisition and maturation of the oral and gut microbiome during the first 1,000 days of life; M2Child (initiated in 2020), which seeks new diagnostic and therapeutic targets for Attention Deficit Hyperactivity Disorder (ADHD) by comprehensively characterising the psychological, biochemical, and oral and gut microbiome profiles; and finally, the Microbi-A project (initiated in 2020), which aims to study the relationship between the oral and gut microbiome and personality traits.

Could you share the most recent and promising discoveries regarding the human microbiome, and how these findings may help us better understand and improve the health/disease balance?
Over the past 20 years, there has been an impressive accumulation of new knowledge, revealing surprising pathways in the relationship between microorganisms and human health. Beyond gaining a deeper understanding of the microbial communities inhabiting our bodies, we are now beginning to better comprehend how these communities interact with human physiology and their role in regulating the health-disease balance. Additionally, microbial communities (detected through DNA analysis) have been described in previously considered sterile sites of the human body, such as the upper urinary system, lower respiratory system, and even tissues and organs. The scientific community is still investigating their actual existence and potential role in human health. In my opinion, some of the most promising discoveries include associations between the human microbiome and metabolic diseases (such as obesity, type 2 diabetes, insulin resistance, and hypertension), mental illness (such as depression, anxiety, and neurodevelopmental disorders), and the effectiveness of immunotherapies (for instance, in the treatment of cancer). Manipulating the microbiome through specific diets or probiotic and/or prebiotic supplements - or even through the transplantation of faecal microbiota from healthy individuals - may, in the future, help prevent or reverse metabolic diseases and promote mental health. Regarding the effectiveness of immunotherapies, it has been reported that greater gut microbial diversity is associated with a better response to immunotherapy. As a result, it has been proposed that the gut microbial profile could be used as a predictive marker for treatment efficacy, allowing for more personalised therapeutic approaches.

What are the current research leads that you would like to pursue, which, in your opinion, hold the greatest potential in microbiome studies?
There are several promising research lines in microbiome studies that I would like to pursue due to their significant potential impact on various areas of human health. One important area is microbiome acquisition and maturation. Studying its development during the early years of life and its connection to disease development later in life, such as oral, metabolic, immune, and mental disorders, holds tremendous potential. Another promising avenue is the oral microbiome and systemic pathology. Although less studied, the oral microbiome has been implicated in various systemic diseases, including cardiovascular, metabolic, and neurodegenerative conditions. Investigating how the oral microbiome can serve as an early biomarker for these diseases or how its modulation can reduce systemic risk is an area I would like to further explore. Finally, the relationship between the human microbiome and mental health is a fascinating and emerging field with profound implications. Understanding how microbiome-based interventions, such as diet, probiotics or prebiotics, or faecal transplantation, can influence mental health is a promising avenue. These areas not only have great potential to improve our scientific understanding of the microbiome but may also lead to innovative and more effective clinical interventions in the future, following a translational logic. The projects I am currently involved in aim to address some of these questions, and we await the results.

Among the many projects you have led or collaborated on, and we've already gone through some of them, we would like to focus on Microbi-A, which studies the relationship between the microbiome and personality traits. Could you share how this research path emerged and what the expected final outcomes are?
As previously mentioned, the association between the microbiome and mental health has been gaining significant relevance. The Microbi-A project emerged after I met Professor Fernando Barbosa from the Faculty of Psychology and Educational Sciences at the University of Porto (FPCEUP) during a continuing education programme. His research focuses on antisocial personality traits. Shortly afterwards, I was planning a PhD project for a new student, Carolina Costa, who expressed a strong interest in studying the microbiota-brain axis, particularly personality traits. Following several meetings between Carolina Costa, Professor Fernando Barbosa, and myself, we designed the project to understand the association between the oral and gut microbiome and personality traits. Professor Philip Burnet from the University of Oxford was invited to join the project and the supervisory team, bringing invaluable expertise to Microbi-A. We hope to identify associations between oral or gut microbial profiles and specific personality traits. This project also explores factors influencing microbial profiles, such as diet, physical activity, medical history, and demographic aspects, as well as circulating molecules associated with microbial metabolism, to better understand the factors that may condition the microbial profile changes we identify.

How do you envisage the role of microbiome research in shaping future strategies to improve healthcare and public health globally?
Microbiome research offers a revolutionary perspective for healthcare and public health. As knowledge expands, we can anticipate a future where prevention, treatment, and health promotion become much more personalised, eco-friendly, and integrated, with the microbiome as one of the pillars of human health. The recent application of meta-omics approaches (metagenomics, metatranscriptomics, metaproteomics, and metabolomics) to clinical samples enables efficient characterisation of microbial communities (at the strain level) and the assessment of metabolic activity occurring in this ecological niche. This allows the identification of microbial species, metabolic pathways, and metabolites associated with disease development and treatment. I believe this comprehensive strategy will, in the future, enable healthcare to be tailored based on each individual's microbial profile, leading to more personalised, targeted, and effective treatments and interventions. We know that the microbiome is unique to each person and that many therapeutic strategies can be influenced by different microbial profiles. Thus, the development of techniques or structures that enable precise predictions of drug-host-microbiome interactions will pave the way for microbiome-based precision medicine. Furthermore, microbiome research can also play a crucial role in addressing emerging public health crises, such as metabolic, autoimmune, and mental disorders, by providing a new understanding of their underlying causes and opening avenues for more effective intervention strategies.

In the field of oral microbiology, could you share an example of how research in this area has directly impacted clinical dentistry practices?
In oral microbiology, the study of the relationship between the microbiome and oral health has led to significant advancements that directly impact clinical dental practices. A clear example is the role of the oral microbiota in the development of dental caries and periodontal disease and how treatments have evolved based on knowledge of microbial ecology. Studies have shown that the development of periodontal diseases, such as gingivitis and periodontitis, is not merely due to the presence of specific bacteria but rather to an imbalance in the oral ecosystem. This imbalance, known as dysbiosis, promotes the growth of pathogenic bacteria, triggering inflammation and tissue destruction. This understanding has led to more targeted therapies in clinical practice, such as the use of oral probiotics to restore microbiome balance rather than indiscriminately eradicating all bacteria. For instance, the use of antibacterial mouthwashes is now more judicious to avoid unnecessary disturbances in the healthy oral microbiome. In terms of dental caries, the placement of fissure sealants as a preventive approach emerged to prevent the adhesion of acidogenic bacteria. As mentioned earlier, there are also important links between oral health and systemic diseases such as chronic kidney disease, diabetes, cardiovascular disease, and Alzheimer's disease, where identifying changes in the oral microbiome can serve as an early biomarker for diagnosing these conditions.

Could you share some of the challenges you've encountered in microbiology research, and what strategies have you adopted to address these challenges?
In microbiome research, we face many challenges on a daily basis. One of the main ones is the lack of funding, which is a chronic issue in research. In microbiome studies, it is particularly relevant because only with regular and robust funding can we access the most comprehensive and up-to-date strategies, leading to more detailed and complete conclusions. Without funding, studies unfortunately progress more slowly and with a more limited scope. Beyond this critical aspect, and looking more at the laboratory context, there is still a significant lack of international standardisation in protocols for sample collection and storage, genetic material extraction, and sequencing methods. This often limits broader comparisons between studies from different laboratories, reducing result reproducibility and generalisation. At the laboratory level, we have addressed this challenge by following international guidelines and adopting protocols that are validated by leading laboratories in the field. Data analysis is also a significant challenge due to the high complexity and vast amount of information generated by high-throughput sequencing. One solution we have adopted is a strong investment in developing an in-house bioinformatics capacity, as well as collaborating with bioinformatics experts who support data analysis and interpretation. Additionally, we have implemented specific training for our team to ensure a better understanding of the analysis and critical assessment of the results. Finally, another major challenge lies in translating research findings into clinical practice. The process of translating discoveries from microbiome studies into effective, evidence-based clinical guidelines is time-consuming and challenging. One of our strategies is to collaborate with clinicians and other health professionals from the early stages of project design to ensure that our research has a strong translational component and clinical relevance.

In your opinion, what simple yet effective strategies can we adopt in our daily lives to improve our microbiome?
Having a very varied diet is key, as our microorganisms also “feed” on what we ingest daily. By having a varied diet, we enhance microbial diversity, which is believed to be more closely associated with good health. Improving the human microbiome can be achieved through simple strategies based on the latest scientific evidence. Some recommendations include a fiber-rich diet, consuming more fruits, vegetables, whole grains, legumes, and nuts, which help feed the beneficial gut bacteria. These foods are rich in fiber, promoting microbiome diversity, which is essential for overall health. Including fermented foods, such as yogurt, kefir, sauerkraut, miso, and kombucha, can also increase the presence of beneficial bacteria. Additionally, probiotic supplements can be considered, although foods are generally preferred. I also recommend reducing sugar and processed food consumption. Studies indicate that diets rich in sugar and ultra-processed foods are associated with lower gut microbiota diversity and an increase in harmful bacteria, contributing to inflammation and chronic diseases. Regular contact with nature, such as gardening or spending time outdoors, increases exposure to a wider variety of beneficial microorganisms, promoting microbial diversity. Avoiding excessive antibiotic use is also crucial, as indiscriminate antibiotic use can eliminate both harmful and beneficial bacteria. It is important to use them only when necessary and always under medical guidance. Maintaining proper hydration is essential: drinking enough water is necessary to maintain intestinal health and, consequently, balance in our microbiome. Lastly, getting good sleep and reducing stress is critical. Chronic stress and lack of sleep negatively affect the human microbiome. Adopting habits that promote good sleep quality and stress management, such as meditation or yoga, can help improve gut health. These strategies are practical and accessible, based on scientific evidence that demonstrates their effectiveness in promoting a balanced microbiome and, consequently, improved overall health.

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