The Effects of Lactobacillus and/or Bifidobacterium in Fermented Foods on Cognitive Health: A Systematic Review

Hayriye Sebnem Harsa^1*CARMEN MARIA GONZALEZ DOMENECH²Milica Prvulovic³Zeynep Agirbasli¹Erfan Bagherzadehsurbagh⁴Valentina Simeunović³Eleni Naziri⁵Elizabeth Adesemoye⁶Aycan Cinar⁷Arghya Mukherjee⁸Marta Laranjo⁹Bojana B Vidovic¹⁰Emilia Alves¹¹Andjela Vukojevic³Sine Özmen Toğay¹²Gamze Düven¹³Helen Saar¹⁴Seppo Salminen¹⁵Guy Vergères¹⁶Antonia Matalas¹⁷Diana Paveljšek¹⁸Else Schneider¹⁹Timur Liwinski²⁰Cornelia Bär^21*Smilja Praćer²²

• ¹Faculty of Engineering, Department Food Engineering, Gulbahce Campus 35430 İzmir, Izmir Yuksek Teknoloji Enstitusu, Urla, Türkiye
• ²Department of Microbiology, Universidad de Malaga Facultad de Medicina, Málaga, Spain
• ³Institute for Biological Research “Sinisa Stankovic”, National Institute of Republic of Serbia, Univerzitet u Beogradu, Belgrade, Serbia
• ⁴Department of Food Engineering, Institute of Natural and Applied Sciences, Akdeniz Universitesi, Antalya, Türkiye
• ⁵Department of Food Science and Nutrition, School of Environment, University of the Aegean, Lemnos, Greece
• ⁶Department of Microbiology, Faculty of Science, Federal University Oye Ekiti, Ekiti, Nigeria
• ⁷Department of Food Engineering, Faculty of Engineering and Natural Sciences, Bursa Teknik Universitesi, Bursa, Türkiye
• ⁸Department of Food Biosciences, Teagasc Food Research Centre Moorepark, Fermoy, Ireland
• ⁹Mediterranean Institute for Agriculture, Environment and Development & Global Change and Sustainability Institute, Departamento de Medicina Veterinária, Escola de Ciências e Tecnologia, Pólo da Mitra, Universidade de Evora, Evora, Portugal
• ¹⁰Department of Bromatology, Faculty of Pharmacy, Univerzitet u Beogradu, Belgrade, Serbia
• ¹¹CBIOS - Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Lisbon, Portugal
• ¹²Department of Food Engineering, Faculty of Agriculture, Bursa, Bursa Uludag Universitesi, Nilüfer, Türkiye
• ¹³Milk and Dairy Technology Programme, Department of Food Processing, Karacabey Vocational School, Bursa, Bursa Uludag Universitesi, Nilüfer, Türkiye
• ¹⁴Research Services, AS TFTAK, Tallinn, Estonia
• ¹⁵University of Turku, Functional Foods Forum, Faculty of Medicine, Itäinen Pitkäkatu 4A, FI-20014, Southwest Finland, Turku, Finland
• ¹⁶Strategic Research Division Food Microbial Systems, Functional Nutritional Biology, Schwarzenburgstrasse 161, CH-3003, Agroscope, Bern, Switzerland
• ¹⁷Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece
• ¹⁸Biotechnical Faculty, Univerza v Ljubljani, Ljubljana, Slovenia
• ¹⁹Center for Affective, Stress and Sleep Disorders, University Psychiatric Clinics (UPK), Universitare Psychiatrische Kliniken Basel, Basel, Switzerland
• ²⁰Experimental Cognitive and Clinical Affective Neuroscience (ECAN) Laboratory, University of Basel, Department of Clinical Research (DKF), Universitare Psychiatrische Kliniken Basel, Basel, Switzerland
• ²¹Competence Division Methods Development and Analytics, Biochemistry of Milk and Microorganisms, Schwarzenburgstrasse 161, CH-3003, Agroscope, Bern, Switzerland
• ²²Department of Neurobiology, Institute for Biological Research “Sinisa Stankovic”, National Institute of the Republic of Serbia, Univerzitet u Beogradu, Belgrade, Serbia

Background: Psychobiotics are microorganisms that modulate brain function via the gut–brain axis and are increasingly studied for their cognitive benefits. Lactobacillus and Bifidobacterium species, widely present in fermented foods, are considered safe and may influence cognition by modulating neuroinflammation, neurotransmitters, and gut barrier integrity. This systematic review examined the effects of foods fermented with these species on cognitive performance in healthy adults and individuals with mild cognitive impairment. Methods: We conducted the systematic review following EFSA guidelines, Cochrane methodology, and a PROSPERO protocol, using CADIMA for study selection and data extraction. PubMed, Scopus, and Cochrane Library were searched (1 January 1970–31 August 2023) for human intervention and observational studies assessing cognitive outcomes after ingestion of foods fermented with Lactobacillus or Bifidobacterium. Eligible populations included healthy adults and individuals with mild cognitive impairment; studies involving disease were excluded. Screening, data extraction, and bias assessment followed Muka et al.'s 24-step guide using ROBINS and Cochrane/CADIMA frameworks. Evidence was synthesized narratively, while a non-systematic component examined food characteristics, potential mechanisms, and factors affecting bioavailability of bioactive constituents. Results: We included 21 studies (8 interventional, 13 observational). The majority of studies reported benefits, particularly in episodic memory, executive functions, and global cognition, but evidence was limited by inadequate controls, small sample sizes, short interventions, inconsistent domain assessment, and incomplete food characterization. Observational studies had larger populations and longer follow-ups but were limited by exposure assessment and depth of cognitive testing. Conclusions: Consumption of foods fermented with Lactobacillus and/or Bifidobacterium species may offer promising cognitive benefits. However, following EFSA's guidance on the substantiation of health claims, the current evidence is "neither convincing nor sufficient" to establish a causal relationship. Well-designed studies with thorough product characterization are needed to substantiate effects and support potential health claims. Systematic Review Registration: This study was registered at the Open Science Framework (https://doi.org/10.17605/OSF.IO/Z6GRW).