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. 2024 Jan 8;14:799. doi: 10.1038/s41598-023-50190-5

Exploring public interest in gut microbiome dysbiosis, NAFLD, and probiotics using Google Trends

Salvatore Pezzino 1, Maria Sofia 1, Chiara Mazzone 1, Giorgia Litrico 1, Marcello Agosta 1, Gaetano La Greca 1, Saverio Latteri 1,✉
PMCID: PMC10774379  PMID: 38191502

Abstract

Scientific interest related to the role of gut microbiome dysbiosis in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has now been established and is constantly growing. Therefore, balancing dysbiosis, through probiotics, would be a potential therapy. In addition to scientific interest, on the other hand, it is important to evaluate the interest in these topics among the population. This study aimed to analyze, temporally and geographically, the public's interest in gut microbiome dysbiosis, NAFLD, and the use of gut probiotics. The most widely used free tool for analyzing online behavior is Google Trends. Using Google Trends data, we have analyzed worldwide volume searches for the terms “gut microbiome”, “dysbiosis”, “NAFLD” and “gut probiotic” for the period from 1, January 2007 to 31 December 2022. Google's relative search volume (RSV) was collected for all terms and analyzed temporally and geographically. The RSV for the term “gut microbiome” has a growth rate of more than 1400% followed, by “gut probiotics” (829%), NAFLD (795%), and “dysbiosis” (267%) from 2007 to 2012. In Australia and New Zealand, we found the highest RSV score for the term “dysbiosis” and “gut probiotics”. Moreover, we found the highest RSV score for the term “NAFLD” in the three countries: South Korea, Singapore, and the Philippines. Google Trends analysis showed that people all over the world are interested in and aware of gut microbiome dysbiosis, NAFLD, and the use of gut probiotics. These data change over time and have a geographical distribution that could reflect the epidemiological worldwide condition of NAFLD and the state of the probiotic market.

Subject terms: Microbiota, Liver diseases

Introduction

The human digestive system is hosted to between 500 and 1000 types of commensal bacteria, the great majority of which are anaerobic1,2. The gut microbiome’s dysbiosis has been associated with several disorders, including chronic inflammation3, neurological and ophthalmic diseases4,5, and chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), a condition caused by an excessive accumulation of fat in hepatocytes6–8. By 2030, the rate of increase in NAFLD incidence is expected to be quadruplicated9,10. The epidemic rise of NAFLD can be attributed in large part to the modern plagues of sedentary living, high-calorie diets, and low levels of physical activity11,12. One of the etiologies of NAFLD has been linked to dysbiosis in the gut microbiome. There is mounting evidence from both preclinical and clinical studies demonstrating that gut dysbiosis is a significant element in the development of this dysfunction and that this disturbance plays a substantial role in NAFLD pathogenesis6–8,13–17.

A probiotic is “live bacteria that, when administered in suitable proportions, provide health benefits to the host”18. Studies on the efficacy of probiotics in reversing dysbiosis have shown encouraging results19–21. In a number of studies, both preclinical and clinical, probiotics have shown promise in correcting gut dysbiosis and clinical markers of NAFLD illness22–27.

Scientific interest related to the role of gut microbiome dysbiosis in the pathogenesis of NAFLD has now been established and is constantly growing6,14,17. Therefore, balancing dysbiosis, through probiotics, would be a potential therapy20,21. In addition to scientific interest, on the other hand, it is important to evaluate the interest in these topics among the population. The most widely used free tool for analyzing online behavior is Google Trends, which can also give real-time data about trends and changes in online interest over time for different terms and themes28–30. Electronic data is utilized in this field to monitor online interest in health problems and procedures, predict disease outbreaks, and assess the efficacy of health education efforts31. For example, in a recent study, Mikoła et al. showed how interest in probiotic-related information may be correlated with antibiotic consumption, health expenditures, and the country's level of development32,33.

The purpose of our study is to analyze, temporally and geographically, the public's interest related to gut microbiome dysbiosis, NAFLD, and the use of gut probiotics using Google Trends data, so that physicians and researchers should not only be aware of the hotspots of scientific research but also of the concerns of public interest.

Results

Relative search volume (RSV) trend

Figure 1 depicts the overall global RSV trends for all four searched terms from 2007 to 2022. RSV grew from 45 to about 293. There was a small negative decline between 2008 and 2012. Despite minor fluctuations, the average search strength demonstrated an overall upward tendency. The curve started to rise again in 2013.

Figure 1.

Figure 1

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World annual mean trend of the RSV (relative search volume) from January 2007 until December 2022 (15 years), given by the sum of the mean RSV value of each searched term from Google Trends, data accessed on January 18, 2023.

Among the four searched terms, “gut microbiome” and “gut probiotics”, changed respectively from an RSV of 6 and 7.4 to an RSV of 86.3 and 61.2. While “dysbiosis” and “NAFLD" have respectively an increase from 19.9 and 11.7 to 53.2 and 92.8 (Fig. 2).

Figure 2.

Figure 2

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World annual mean trend of the RSV (relative search volume) from January 2007 until December 2022 (15 years) for every single searched term: “gut microbiome”, “dysbiosis”, “NAFLD” and “gut probiotics” from Google Trends. RSV: relative search volumes; data accessed on January 18, 2023.

When comparing the RSV value for the year 2022 to the value for the year 2007 for all four words (Fig. 3), the term “gut microbiome” shows a growth of about 1400%, followed by "gut probiotics" (829%), NAFLD (795%), and “dysbiosis” with 267%.

Figure 3.

Figure 3

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The ratio (%) between the RSV (relative search volume) value of the year 2022 and the value of the year 2007 for the searched terms: “gut microbiome, “dysbiosis”, “NAFLD” and “gut probiotics.

Country relative search volume (RSV) distribution

The geographic distribution graph for each searched term from 2007 to 2022 is shown in Fig. 4, while Table 1 shows the country RSV value for searched terms.

Figure 4.

Figure 4

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Geographic distribution of the RSV (relative search volume) for the searched terms from Google Trends: “gut microbiome” is colored in blue, “dysbiosis” is colored in red, "NAFLD" is colored in yellow, and “gut probiotics” is colored in green. The color gradient is proportional to the value of RSV; data accessed on January 18, 2023.

Table 1.

Country RSV (relative search volume) value for searched terms: “gut microbiome”, “dysbiosis”, “NAFLD,” and “gut probiotics” from Google Trends.

Country gut microbiome (RSV) Country dysbiosis (RSV) Country NAFLD (RSV) Country gut probiotics (RSV)
Australia 100 Australia 100 Argentina 6 Australia 100
Austria 19 Belgium 12 Australia 55 Canada 60
Bangladesh 27 Brazil 4 Austria 28 Germany 3
Belgium 19 Canada 61 Bangladesh 50 India 14
Brazil 6 Egypt 16 Belgium 24 Ireland 78
Canada 61 France 5 Brazil 5 Malaysia 24
China 41 Germany 6 Canada 56 Netherlands 8
Denmark 37 Hong Kong 46 Chile 15 New Zealand 81
Egypt 16 Hungary 19 China 23 Nigeria 16
Finland 20 India 16 Colombia 8 Pakistan 16
France 7 Indonesia 8 Croatia 19 Philippines 23
Germany 12 Iran 9 Czechia 22 Singapore 68
Greece 16 Iraq 23 Denmark 25 South Africa 44
Hong Kong 71 Ireland 70 Egypt 46 Spain 2
India 23 Italy 6 Finland 16 United Arab Emirates 26
Indonesia 11 Japan 7 France 10 United Kingdom 52
Iran 8 Kenya 22 Germany 15 United States 57
Ireland 90 Malaysia 18 Greece 36
Israel 25 Mexico 6 Hong Kong 47
Italy 9 Netherlands 13 India 41
Japan 7 New Zealand 82 Indonesia 13
Malaysia 25 Nigeria 19 Iran 25
Mexico 6 Norway 23 Iraq 28
Netherlands 29 Pakistan 21 Ireland 47
New Zealand 71 Philippines 21 Israel 29
Nigeria 23 Poland 4 Italy 30
Norway 25 Romania 11 Japan 32
Pakistan 28 Russia 4 Malaysia 33
Philippines 25 Saudi Arabia 8 Mexico 10
Poland 6 Singapore 35 Netherlands 23
Portugal 22 South Africa 37 New Zealand 47
Romania 12 South Korea 36 Nigeria 20
Russia 4 Spain 7 Pakistan 43
Singapore 75 Sweden 19 Peru 11
South Africa 39 Swiss 18 Philippines 73
South Korea 84 Taiwan 23 Poland 16
Spain 10 Thailand 11 Portugal 27
Sweden 23 Turkey 4 Romania 15
Swiss 27 Ukraine 6 Russia 3
Taiwan 22 United Arab Emirates 23 Saudi Arabia 22
Thailand 17 United Kingdom 45 Singapore 73
Turkey 4 United States 55 Slovakia 26
United Arab Emirates 20 Vietnam 3 South Africa 22
United Kingdom 53 South Korea 100
United States 68 Spain 15
Vietnam 11 Sri Lanka 51
Sweden 25
Swiss 34
Taiwan 29
Thailand 21
Turkey 6
United Arab Emirates 30
United Kingdom 67
United States 50
Vietnam 5
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RSV was calculated from searches for all four terms in the corresponding country (from January 1, 2007, to December 31, 2022). Only countries with data in at least one of the four terms are included. The data are sorted by country name in descending order; the data were accessed on January 18, 2023.

The top ten countries with the highest RSV for the term “gut microbiome” are Australia (RSV = 100), Ireland (RSV = 90), South Korea (RSV = 84), Singapore (RSV = 75), New Zealand (RSV = 71), Hong Kong (RSV = 71), United States (RSV = 68), Canada (RSV = 61), United Kingdom (RSV = 53), China (RSV = 41).

The top ten RSV countries for the term “dysbiosis” are Australia (RSV = 100), New Zealand (RSV = 82), Ireland (RSV = 70), Canada (RSV = 61), United States (RSV = 55), Hong Kong (RSV = 46), United Kingdom (RSV = 45), South Africa (RSV = 37), South Korea (RSV = 36), Singapore (RSV = 35).

For the term “NAFLD”, the top ten are South Korea (RSV = 100), Singapore (RSV = 73), Philippines (RSV = 73), United Kingdom (RSV = 67), Canada (RSV = 56), Australia (RSV = 55), Sri Lanka (RSV = 51), United States (RSV = 50), Bangladesh (RSV = 50), Hong Kong (RSV = 47), Ireland (RSV = 47), New Zealand (RSV = 47), Egypt (RSV = 46).

The following countries are in the top ten ranks for the term “gut probiotics”: Australia (RSV = 100), New Zealand (RSV = 81), Ireland (RSV = 78), Singapore (RSV = 68), Canada (RSV = 60), United States (RSV = 57), United Kingdom (RSV = 52), South Africa (RSV = 44), United Arab Emirates (RSV = 26), Malaysia (RSV = 24).

On the other hand, concerning countries exhibiting the lowest RSV for the term "gut microbiome," the five ranked in ascending order are Russia (RSV = 4), Turkey (RSV = 4), Brazil (RSV = 6), Mexico (RSV = 6) and Poland (RSV = 6).

Instead, the five countries that rank lowest for the term “dysbiosis” are Vietnam (RSV = 3), Brazil (RSV = 4), Poland (RSV = 4), Russia (RSV = 4) and Turkey (RSV = 4).

For the term “NAFLD” are Russia (RSV = 3), Brazil (RSV = 5), Vietnam (RSV = 5), Argentina (RSV = 6), and Turkey (RSV = 6).

Finally, the five countries with the lowest RSV for the term “gut probiotics” are Spain (RSV = 2), Germany (RSV = 3), the Netherlands (RSV = 8), India (RSV = 14), and Nigeria (RSV = 16).

Relative search volume (RSV) of associated queries

The top ten queries related to the searched terms from 2007 to 2022 are listed in Table 2.

Table 2.

The most used related topics for the period 2007–2022, from Google Trends.

gut microbiome RSV dysbiosis RSV NAFLD RSV gut probiotics RSV
the gut microbiome 100 gut 100 nafld liver 100 probiotics for gut 100
human gut 43 dysbiosis symptoms 25 liver 94 gut health probiotics 87
human microbiome 41 what is dysbiosis 20 nafld nash 62 gut health 86
human gut microbiome 41 microbiota dysbiosis 18 nash 62 probiotics for gut health 49
gut health 35 microbiota 18 nafld score 50 best probiotics 45
gut microbiome bacteria 27 dysbiosis diet 18 fatty liver 46 best gut probiotics 44
gut bacteria 27 microbiome dysbiosis 17 nafld disease 39 probiotic 41
gut microbiota 26 microbiome 17 fibrosis 28 gut bacteria 30
bacteria 26 dysbiosis definition 17 liver disease 27 leaky gut 29
microbiota 26 dysbiosis treatment 16 nafld fibrosis score 20 good probiotics 21
the human microbiome 23 dysbiosis meaning 14 fibrosis score 20 good gut probiotics 20
what is gut microbiome 19 dysbiosis test 12 nafld diet 20 best probiotics for gut health 19
what is microbiome 19 probiotics 10 nafld symptoms 18 probiotics foods 17
microbiome diet 18 gut microbiota 10 fatty liver disease 17 what is gut 15
gut microbiome diet 18 gut microbiota dysbiosis 10 nafld treatment 16 what is probiotics 14
gut microbiome disease 15 dysbiosis of the gut 10 what is nafld 15 best probiotic 14
microbiome test 14 candida 9 cirrhosis 14 gut flora 14
healthy gut 14 bacterial dysbiosis 9 nafld cirrhosis 14 prebiotics 13
healthy gut microbiome 14 sibo 9 nash liver 13 healthy gut 12
what is the gut microbiome 12 leaky gut 8 nafld medical abbreviation 11 probiotics for leaky gut 11
what is the microbiome 12 gut dysbiosis symptoms 8 icd 10 nafld 11 probiotic for gut health 11
gut microbiome foods 12 gut microbiome dysbiosis 7 alt 10 probiotics food 11
gut microbiome brain 11 microbial dysbiosis 7 nafld vs nash 9 probiotics supplements 10
gut microbiome and disease 11 gut microbiome 7 nafld causes 9 microbiome 9
probiotics 10 probiotic 6 steatosis 8 gut microbiome 9
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Users who searched for the terms “gut microbiome”, “dysbiosis”, “NAFLD”, and “gut probiotics”, also searched for these topics. The score is on a relative scale: 100 indicates the most searched query, and 50 indicates a query with half the searches compared to the most searched query; RSV = relative search volume; data accessed on January 18, 2023.

Among the top-ten topics related to the term “gut microbiome”, apart from the variation with the article of the search term (the gut microbiome = 100 RSV), we found human gut (RSV = 43), human microbiome (RSV = 41) and human gut microbiome (RSV = 41), gut health (RSV = 35), gut microbiome bacteria (RSV = 27) and gut bacteria (RSV = 27), gut microbiota (RSV = 26), bacteria (RSV = 26) and microbiota (RSV = 26).

Among the most closely connected topics to “dysbiosis” term, we observed: gut (RSV = 100), dysbiosis symptoms (RSV = 25), what is dysbiosis (RSV = 20), microbiota dysbiosis (RSV = 18), microbiota (RSV = 18), dysbiosis diet (RSV = 18), microbiome dysbiosis (RSV = 17), microbiome (RSV = 17), dysbiosis definition (RSV = 17), dysbiosis treatment (RSV = 16).

The top ten results for "NAFLD," are the following: nafld liver (RSV = 100), liver (RSV = 94), nafld nash (RSV = 62), nash (RSV = 62), nafld score (RSV = 50), fatty liver (RSV = 46), nafld disease (RSV = 39), fibrosis (RSV = 28), liver disease (RSV = 27), nafld fibrosis score (RSV = 20), fibrosis score (RSV = 20), nafld diet (RSV = 20).

Top-related topics to "gut probiotics" include probiotics for gut (RSV = 100), gut health probiotics (RSV = 87), gut health (RSV = 86), probiotics for gut health (RSV = 49), best probiotics (RSV = 45), best gut probiotics (RSV = 44), probiotic (RSV = 41), gut bacteria (RSV = 30), leaky gut (RSV = 29), good probiotics (RSV = 21).

Discussion

Nowadays, open data from the internet is being used more and more in health research. Understanding and monitoring public perceptions of disease management and treatment are equally crucial. Google Trends is rapidly becoming the most popular tool for recognizing internet activity34. In our study using Google search traffic data, we observed public interest and knowledge consisting of annual trends, geographic distribution and related topics related to gut microbiome dysbiosis, NAFLD, and the usage of gut probiotics.

RSV annual trend showed an overall increasing trend, although with slight fluctuation, and a decline in RSV from years 2008 to 2012 (Fig. 1). The increase is higher, especially in the last year, with an RSV that varies from a value of 224.9 to a value of 293.3.

Observing the distinct search terms, we could find that those with a considerable increase in RSV values are those related to the terms "gut microbiome", followed by "gut probiotics", “NAFLD” and finally “dysbiosis” (Fig. 2).

Looking at the 2022 to 2007 RSV ratio data (Fig. 3), we found that all search terms follow a significant percentage increase: the term "gut microbiome" has a growth of more than 1 400%, followed by "gut probiotics" (829%), NAFLD (795%), and "dysbiosis" with 267%.

These trends over time reflect the growing research interest in the dysbiosis of the gut microbiome, its role in several diseases including NAFLD and the interest in gut probiotics as a therapy to restore dysbiosis.

In recent years, the demand for probiotic bacteria-containing products has increased. More and more people are adding probiotic bacteria to their diets as functional food supplements because of the positive effects they have on health35–37. When it comes to functional food ingredients, probiotics are by far the most popular choice. Studies have shown that probiotic strains can help treat a number of illnesses, including gastrointestinal distress, bacterial vaginosis, and urinary tract infections38–40. Protection from dangerous bacteria in the digestive tract, better bowel movement, reduced cholesterol levels, relief from lactose intolerance and inflammation, and so on are just some of the health benefits associated with probiotics41,42.

Another interesting finding in this study was the variation in interest in the searched terms across countries (Fig. 4 and Table 1).

Interestingly, in Australia, and New Zealand, we found the highest RSV score for the term “dysbiosis” and “gut probiotics”. Australia is also in the first rank for the term “gut microbiome”.

From 2021 to 2030, the worldwide probiotics industry is anticipated to increase from 2021’s valuation of about USD 58 billion with a CAGR (compound annual growth rate) of 7.5%43,44. Rising public interest in preventative medicine and the refinement of highly effective probiotic strains are driving the industry. When taken in sufficient quantities, probiotics have positive benefits on the body, including enhanced gastrointestinal wellness and decreased intestinal inflammation45,46. By bolstering the immune system, probiotics play an important role in preventing the onset of illness45,46. Hence, increasing focus on preventative medicine is anticipated to fuel market expansion throughout the forecast period. More than 40.0% of worldwide probiotic market revenue was generated in the Asia Pacific area in 202143,44. Increased consumer awareness is largely attributed to the competitive strategies implemented by multinational companies in the region. Market expansion in the region is anticipated to be driven by a number of factors, including a rising population, rising disposable income, and an increasing standard of life43,44,47. The association between RSV and the topic of probiotics and dysbiosis might be caused by the recommendations of probiotics to restore the gut microbiome12,46.

As far as the “NAFLD” term we found the highest RSV score in the three countries: South Korea, Singapore and the Philippines. An estimated 32.4% of the world's population has NAFLD, and that number has been steadily rising over the past decade48. Among Asian countries, NAFLD is more recent (27%), compared to Europe and North America (24%)49. From 5% in Singapore to 30% in Indonesia, the prevalence of NAFLD in Asia substantially varies50,51. The prevalence of metabolic diseases is on the rise in Korea, from 24.9% in 1998 to 29.0% in 201352. This has become a major public health issue50,51. In Singapore, the number of people living with NAFLD is expected to increase from 1,492,000 in 2019 to 1,799,000 in 203053. In addition, it is concerning that at least one-third of the general population in the Philippines has NAFLD; the prevalence rate is 38%, compared to 25% globally54. It is believed that the rising prevalence of NAFLD in the Asia–Pacific area is due to the widespread adoption of Western food and lifestyle practices and predisposing genetic factors among many different communities55. Rapid industrialization in many Asian nations has led to a shift toward sedentary behaviors and overnutrition, both of which are strongly linked to metabolic problems56. Moreover, despite the fact that obesity and diabetes are well-known risk factors for the disease57,58, a sizable population in the Asian region suffers from NAFLD while having a healthy weight59. It is expected that the number of people diagnosed with NAFLD and NASH throughout Asia will continue to rise, especially in rapidly aging populations, who are more likely to develop chronic lifestyle-related illnesses60.

The top ten related queries in terms of searches from 2007 to 2022 are listed in Table 2. The queries related to the term "gut microbiome", are related to understanding by the public of what the gut microbiome is, what bacteria it consists of, how to diagnose gut dysbiosis, and how to keep it healthy through diet, food, and also probiotics. In addition, some search terms refer to the link between the gut and brain, the so-called gut-brain axis. The gut-liver axis is increasingly being recognized as the underlying cause of NAFLD14,16,17. By dysregulating the gut-liver axis, gut microbiome dysbiosis, which contributes to the development of NAFLD, promotes an increase in intestinal permeability and uncontrolled transport of microbial metabolites into the liver14,16,17. Moreover, NAFLD is facilitated by a dysfunctional gut-liver axis, which affects hepatocyte lipid and glucose metabolism and disturbs the equilibrium of inflammatory mediators14,16,17.

The public queries related to the term "dysbiosis" are related to its definition, the pathogenetic mechanisms that underlie it, possible diagnosis, and treatment.

The queries related to the term "NAFLD" are related to its definition and pathogenetic mechanisms, the correlation with non-alcoholic steatohepatitis (NASH), the diagnosis of fibrosis, and care through diet. Research has connected dysbiosis in the gut microbiome not only to the development of NAFLD but also to its progression in NASH, which is characterized histologically by hepatocyte damage and various degrees of fibrosis, up until cirrhosis6–8,13.

The queries related to the terms “gut probiotics” are related to the public's search for an "effective" probiotic treatment. Among related queries to “gut probiotics” appear also the terms “leaky” or “probiotics for the leaky gut”. The intestinal barrier permits communication between the digestive tract and the liver61,62. Tight connections between intestinal cells are essential for maintaining the integrity of the intestinal barrier63. A leaky gut, defined by decreased intestinal barrier function, is a well-established characteristic of dysbiosis in NAFLD patients64,65. Dysbiosis and associated reduced gut permeability results in an increase in gut-derived toxins in the systemic circulation, constituting metabolic endotoxemia, which contributes to the development of the persistent low-grade inflammation observed in NAFLD65,66.

In conclusion, Google Trends analysis showed that people all over the world are interested in and aware of gut microbiome dysbiosis, NAFLD, and the use of gut probiotics. These data change over time and have a geographical distribution that could reflect the epidemiological worldwide condition of NAFLD and the state of the probiotic market. The collection of such information has the potential to improve the monitoring of numerous diseases in the future. A number of variables limit Google Trends' applicability. Because Google Trends removes queries from the same person over a short time period to reduce counts of continued searching, the service may suffer from sampling bias. Google's search algorithms are constantly being improved, so the same query terms may provide different results. This will make it more challenging to replicate these studies, which rely on reproducible results. Whether or not people learn more about health issues as a result of using Google to research them is debatable. This is because Google Trends only reports how often a term has been searched without providing any information on the quality of the results that may be used to gauge how much useful information can be gleaned from them. Another limitation that could affect our analysis is that the internet is becoming increasingly widespread, embracing an increasingly wide range of populations. Now, you can access the internet with different devices, such as smartphones.

Methods

Data from Google Trends is expressed as relative search volume (RSV). The RSV is presented on a standardized scale from 0 (no search interest) to 100 (greatest search interest). We have searched worldwide RSV for the English terms “gut microbiome, “dysbiosis”, “NAFLD” and “gut probiotics”. The search was limited to the period from 1 January 2007 to 31 December 2022. Data related to the public interest was downloaded in “csv” format from the Google Trends website34 on January 18, 2023. Since the data fluctuates over time, we have processed the data, which is shown as an annual average of the monthly values of RSV from 1 January 2007 to 31 December 2022. Our analysis used the country option to determine the geographical distribution of RSV for each searched term. Google Trends can also identify searches that are connected to a given search term and categorize these searches as “queries.” The top searches option displays popular search phrases that are comparable to the keyword input, during a specific time period. We analyze the 'top' searches for each term “gut microbiome, “dysbiosis”, “NAFLD” and “gut probiotics”.

Acknowledgements

This paper was written using data obtained on January 18, 2023, from Google Trends online platforms available at https://trends.google.it/trends.

Author contributions

S.P. and S.L. contributed to the conception and design of the study. S.P. and S.L. prepared the draft of the manuscript. S.P. was a major contributor to writing the manuscript. M.S., C.M., G.L., M.A., G.L.G. reviewed and revised the manuscript. All authors read and approved the final manuscript.

Data availability

The data sets generated and/or analyzed during the current study are available upon request from the corre- sponding author.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

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Data Availability Statement

The data sets generated and/or analyzed during the current study are available upon request from the corre- sponding author.

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