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3. Changes in liver metabolic pathways demonstrate efficacy of the combined dietary and microbial therapeutic intervention in MASLD mouse model.

Author

Iannone, Valeria, Babu, Ambrin, Lok, Johnson, Gómez-Gallego, Carlos, DAuria, Giuseppe, Vazquez-Uribe, Ruben, Vaaben, Troels, Bongers, Mareike, Mikkonen, Santtu, Vaittinen, Maija, Tikkanen, Ida, Kettunen, Mikko, Klåvus, Anton, Sehgal, Ratika, Pihlajamaki, Jussi, Hanhineva, Kati, El-Nezami, Hani, Sommer, Morten, Kolehmainen, Marjukka, and Kaminska, Dorota

Subjects
Aldafermin, Genetically modified E.coli Nissle 1917, Non-alcoholic fatty liver disease, Non-targeted metabolomics, Omics integration, Transcriptomics
Abstract

OBJECTIVE: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent liver disease globally, yet no therapies are approved. The effects of Escherichia coli Nissle 1917 expressing aldafermin, an engineered analog of the intestinal hormone FGF19, in combination with dietary change were investigated as a potential treatment for MASLD. METHODS: MASLD was induced in C57BL/6J male mice by American lifestyle-induced obesity syndrome diet and then switched to a standard chow diet for seven weeks. In addition to the dietary change, the intervention group received genetically engineered E. coli Nissle expressing aldafermin, while control groups received either E. coli Nissle vehicle or no treatment. MASLD-related plasma biomarkers were measured using an automated clinical chemistry analyzer. The liver steatosis was assessed by histology and bioimaging analysis using Fiji (ImageJ) software. The effects of the intervention in the liver were also evaluated by RNA sequencing and liquid-chromatography-based non-targeted metabolomics analysis. Pathway enrichment studies were conducted by integrating the differentially expressed genes from the transcriptomics findings with the metabolites from the metabolomics results using Ingenuity pathway analysis. RESULTS: After the intervention, E. coli Nissle expressing aldafermin along with dietary changes reduced body weight, liver steatosis, plasma aspartate aminotransferase, and plasma cholesterol levels compared to the two control groups. The integration of transcriptomics with non-targeted metabolomics analysis revealed the downregulation of amino acid metabolism and related receptor signaling pathways potentially implicated in the reduction of hepatic steatosis and insulin resistance. Moreover, the downregulation of pathways linked to lipid metabolism and changes in amino acid-related pathways suggested an overall reduction of oxidative stress in the liver. CONCLUSIONS: These data support the potential for using engineered microbial therapeutics in combination with dietary changes for managing MASLD.

Published
2023

4. Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD+ metabolism in humans

Author

U-Din, Mueez, de Mello, Vanessa D, Tuomainen, Marjo, Raiko, Juho, Niemi, Tarja, Fromme, Tobias, Klåvus, Anton, Gautier, Nadine, Haimilahti, Kimmo, Lehtonen, Marko, Kristiansen, Karsten, Newman, John W, Pietiläinen, Kirsi H, Pihlajamäki, Jussi, Amri, Ez-Zoubir, Klingenspor, Martin, Nuutila, Pirjo, Pirinen, Eija, Hanhineva, Kati, and Virtanen, Kirsi A

Subjects
Biological Sciences, Clinical Research, BAT, CP: Metabolism, NAD(+), cold exposure, human brown adipose tissue, nicotinamide, tryptophan, Biochemistry and Cell Biology, Medical Physiology, Biological sciences
Abstract

Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues.

Published
2023

6. Eight-year diet and physical activity intervention affects serum metabolites during childhood and adolescence: A nonrandomized controlled trial

Author

Zarei, Iman, Eloranta, Aino-Maija, Klåvus, Anton, Väistö, Juuso, Lehtonen, Marko, Mikkonen, Santtu, Koistinen, Ville M., Sallinen, Taisa, Haapala, Eero A., Lintu, Niina, Soininen, Sonja, Haikonen, Retu, Atalay, Mustafa, Schwab, Ursula, Auriola, Seppo, Kolehmainen, Marjukka, Hanhineva, Kati, and Lakka, Timo A.

Published
2024
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7. Risk assessment with gut microbiome and metabolite markers in NAFLD development

Author

Leung, Howell, Long, Xiaoxue, Ni, Yueqiong, Qian, Lingling, Nychas, Emmanouil, Siliceo, Sara Leal, Pohl, Dennis, Hanhineva, Kati, Liu, Yan, Xu, Aimin, Nielsen, Henrik B, Belda, Eugeni, Clément, Karine, Loomba, Rohit, Li, Huating, Jia, Weiping, and Panagiotou, Gianni

Subjects
Chronic Liver Disease and Cirrhosis, Hepatitis, Prevention, Nutrition, Liver Disease, Clinical Research, Digestive Diseases, Aetiology, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Biomarkers, Gastrointestinal Microbiome, Humans, Non-alcoholic Fatty Liver Disease, Prospective Studies, Risk Assessment, Biological Sciences, Medical and Health Sciences
Abstract

A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.

Published
2022

10. Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

Author

Zhang, Pei, Carlsten, Christopher, Chaleckis, Romanas, Hanhineva, Kati, Huang, Mengna, Isobe, Tomohiko, Koistinen, Ville M, Meister, Isabel, Papazian, Stefano, Sdougkou, Kalliroi, Xie, Hongyu, Martin, Jonathan W, Rappaport, Stephen M, Tsugawa, Hiroshi, Walker, Douglas I, Woodruff, Tracey J, Wright, Robert O, and Wheelock, Craig E

Subjects
Chemical Engineering, Engineering, Environmental Sciences, Pollution and Contamination, Generic health relevance, Good Health and Well Being, Environmental Science and Management, Environmental Engineering, Environmental Biotechnology, Chemical engineering, Pollution and contamination
Abstract

The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.

Published
2021

22. Blood metabolomic profiling reveals new targets in the management of psychological symptoms associated with alcohol use disorder

Author

Leclercq, Sophie, primary, Ahmed, Hany, additional, Amadieu, Camille, additional, Petit, Géraldine, additional, Koistinen, Ville, additional, Leyrolle, Quentin, additional, Poncin, Marie, additional, Stärkel, Peter, additional, Kok, Eloise, additional, Karhunen, Pekka J., additional, De Timary, Philippe, additional, Layé, Sophie, additional, Neyrinck, Audrey M., additional, Kärkkäinen, Olli, additional, Hanhineva, Kati, additional, and Delzenne, Nathalie M., additional

Published
2024
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23. Eight-year Combined Diet and Physical Activity Intervention Affects Serum Metabolites during Childhood and Adolescence: A Nonrandomized Controlled Trial

Author

Zarei, Iman, primary, Eloranta, Aino-Maija, additional, Klavus, Anton, additional, Vaisto, Juuso, additional, Lehtonen, Marko, additional, Mikkonen, Santtu, additional, Koistinen, Ville M., additional, Sallinen, Taisa, additional, Haapala, Eero A., additional, Lintu, Niina, additional, Soininen, Sonja, additional, Atalay, Mustafa, additional, Schwab, Ursula, additional, Auriola, Seppo, additional, Kolehmainen, Marjukka, additional, Hanhineva, Kati, additional, and Lakka, Timo A., additional

Published
2024
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24. Data sharing in PredRet for accurate prediction of retention time: Application to plant food bioactive compounds

Author

Low, Dorrain Yanwen, Micheau, Pierre, Koistinen, Ville Mikael, Hanhineva, Kati, Abrankó, László, Rodriguez-Mateos, Ana, da Silva, Andreia Bento, van Poucke, Christof, Almeida, Conceição, Andres-Lacueva, Cristina, Rai, Dilip K., Capanoglu, Esra, Tomás Barberán, Francisco A., Mattivi, Fulvio, Schmidt, Gesine, Gürdeniz, Gözde, Valentová, Kateřina, Bresciani, Letizia, Petrásková, Lucie, Dragsted, Lars Ove, Philo, Mark, Ulaszewska, Marynka, Mena, Pedro, González-Domínguez, Raúl, Garcia-Villalba, Rocío, Kamiloglu, Senem, de Pascual-Teresa, Sonia, Durand, Stéphanie, Wiczkowski, Wieslaw, Bronze, Maria Rosário, Stanstrup, Jan, and Manach, Claudine

Published
2021
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26. LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Author

Ronkainen, Justiina, Nedelec, Rozenn, Atehortua, Angelica, Balkhiyarova, Zhanna, Cascarano, Anna, Ngoc Dang, Vien, Elhakeem, Ahmed, van Enckevort, Esther, Goncalves Soares, Ana, Haakma, Sido, Halonen, Miia, Heil, Katharina F., Heiskala, Anni, Hyde, Eleanor, Jacquemin, Bénédicte, Keikkala, Elina, Kerckhoffs, Jules, Klåvus, Anton, Kopinska, Joanna A., Lepeule, Johanna, Marazzi, Francesca, Motoc, Irina, Näätänen, Mari, Ribbenstedt, Anton, Rundblad, Amanda, Savolainen, Otto, Simonetti, Valentina, de Toro Eadie, Nina, Tzala, Evangelia, Ulrich, Anna, Wright, Thomas, Zarei, Iman, d’Amico, Enrico, Belotti, Federico, Brunius, Carl, Castleton, Christopher, Charles, Marie-Aline, Gaillard, Romy, Hanhineva, Kati, Hoek, Gerard, Holven, Kirsten B., Jaddoe, Vincent W. V., Kaakinen, Marika A., Kajantie, Eero, Kavousi, Maryam, Lakka, Timo, Matthews, Jason, Piano Mortari, Andrea, Vääräsmäki, Marja, Voortman, Trudy, Webster, Claire, Zins, Marie, Atella, Vincenzo, Bulgheroni, Maria, Chadeau-Hyam, Marc, Conti, Gabriella, Evans, Jayne, Felix, Janine F., Heude, Barbara, Järvelin, Marjo-Riitta, Kolehmainen, Marjukka, Landberg, Rikard, Lekadir, Karim, Parusso, Stefano, Prokopenko, Inga, de Rooij, Susanne R., Roseboom, Tessa, Swertz, Morris, Timpson, Nicholas, Ulven, Stine M., Vermeulen, Roel, Juola, Teija, Sebert, Sylvain, Sebert, Sylvain, Juola, Teija, Nedelec, Rozenn, Ronkainen, Justiina, Heiskala, Anni, Halonen, Miia, He, Yiyan, Miettunen, Jouko, Karhunen, Ville, Kajantie, Eero, Vääräsmäki, Marja, Keikkala, Elina, Nyberg, Pia, Serpi, Raisa, Felix, Janine, Jaddoe, Vincent, Marques, Irene, Moreira da Silva Santos, Susana, Kavousi, Maryam, Voortman, Trudy, Ginos, Bigina, Chadeau-Hyam, Marc, Järvelin, Marjo-Riitta, Tzala, Evangelia, De Toro, Nina, Wright, Thomas, Bodinier, Barbara, Dagnino, Sonia, Evans, Jayne, Webster, Claire, Kolehmainen, Marjukka, Hanhineva, Kati, Lakka, Timo, Savolainen, Otto, Zarei, Iman, Näätänen, Mari, Klåvus, Anton, Eloranta, Aino-Maija, Väistö, Juuso, Kårlund, Anna, Mikkonen, Santtu, Atalay, Merja, Atalay, Mustafa, Landberg, Rikard, Brunius, Carl, Ribbenstedt, Anton, Swertz, Morris, Hyde, Eleanor, Haakma, Sido, van Enckevort, Esther, Heude, Barbara, Charles, Marie-Aline, Zins, Marie, Lepeule, Johanna, Jacquemin, Bénédicte, Calas, Lucinda, Lequy-Flahault, Emeline, Lun Yuan, Wen, Seyve, Emie, Conti, Gabriella, Vermeulen, Roel, Hoek, Gerard, Kerckhoffs, Jules, Prokopenko, Inga, Kaakinen, Marika, Balkhiyarova, Zhanna, Ulrich, Anna, Roseboom, Tessa, De Rooij, Susanne, Motoc, Irina, Marie Ulven, Stine, Holven, Kirsten B., Matthews, Jason, Rundblad, Amanda, Das, Siddhartha, Timpson, Nicholas, Elhakeem, Ahmed, Luiza Goncalves Soares, Ana, Lekadir, Karim, Maria Cascarano, Anna, Maria Atehortua Labrador, Angélica, Ngoc Dang, Vien, Heil, Katharina F., Gallin, Catherine, Díaz, Oliver, Bulgheroni, Maria, Simonetti, Valentina, D’Amico, Enrico, Giani, Laura, Manzino, Fabrizio, Parusso, Stefano, Castleton, Christopher, Moimas, Diego, Atella, Vincenzo, Piano Mortari, Andrea, Kopinska, Joanna, Marazzi, Francesca, Giaccherini, Matilde, and Belotti, Federico

Published
2022
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27. Association between whole-grain consumption, tryptophan metabolism and psychological distress: a secondary analysis of a randomised controlled trial.

Author

Liikonen, Vilma, Näätänen, Mari, Kårlund, Anna, Hanhineva, Kati, Karhunen, Leila, and Kolehmainen, Marjukka

Subjects
TRYPTOPHAN metabolism, PSYCHOLOGICAL distress, FOOD consumption, BODY mass index, PROPIONIC acid, REGULATION of body weight, QUESTIONNAIRES, GRAIN, ENERGY metabolism, METABOLITES, INDOLE compounds, LIQUID chromatography, FOOD diaries, SEROTONIN
Abstract

This study aimed to investigate whether psychological distress, whole-grain consumption and tryptophan metabolism are associated with participants undergoing weight management intervention. Seventy-nine women and men (mean age 49·7 (sd 9·0) years; BMI 34·2(sd 2·5) kg/m2) participated in a 7-week weight-loss (WL) period and in a 24-week weight maintenance (WM) intervention period. Whole-grain consumption was measured using 4 d food diaries. Psychological distress was assessed with the General Health Questionnaire-12 (GHQ), and participants were divided into three GHQ groups based on the GHQ scores before WL. Tryptophan metabolites were determined from the participants' fasting plasma using liquid chromatography-MS. GHQ scores were not associated with the whole-grain consumption. A positive association was observed between the whole-grain consumption and indole propionic acid (IPA) during the WM (P = 0·033). Serotonin levels were higher after the WL in the lowest GHQ tertile (P = 0·033), while the level at the end of the WM was higher compared with other timepoints in the highest GHQ tertile (P = 0·015 and P = 0·001). This difference between groups was not statistically significant. Furthermore, levels of several tryptophan metabolites changed within the groups during the study. Tryptophan metabolism changed during the study in the whole study group, independently from the level of psychological distress. The association between whole-grain consumption and IPA is possibly explained by the effects of dietary fibre on gut microbiota. This broadens the understanding of the pathways behind the health benefits associated with the intake of whole grains. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Changes in liver metabolic pathways demonstrate efficacy of the combined dietary and microbial therapeutic intervention in MASLD mouse model

Author

Iannone, Valeria, primary, Babu, Ambrin Farizah, additional, Lok, Johnson, additional, Gómez-Gallego, Carlos, additional, D’Auria, Giuseppe, additional, Vazquez-Uribe, Ruben, additional, Vaaben, Troels Holger, additional, Bongers, Mareike, additional, Mikkonen, Santtu, additional, Vaittinen, Maija, additional, Tikkanen, Ida, additional, Kettunen, Mikko, additional, Klåvus, Anton, additional, Sehgal, Ratika, additional, Kaminska, Dorota, additional, Pihlajamaki, Jussi, additional, Hanhineva, Kati, additional, El-Nezami, Hani, additional, Alexander Sommer, Morten Otto, additional, and Kolehmainen, Marjukka, additional

Published
2023
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42. Biomarkers of cereal food intake

Author

Landberg, Rikard, Hanhineva, Kati, Tuohy, Kieran, Garcia-Aloy, Mar, Biskup, Izabela, Llorach, Rafael, Yin, Xiaofei, Brennan, Lorraine, and Kolehmainen, Marjukka

Published
2019
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