Impact of vitamin deficiency on microbiota composition and immunomodulation: relevance to autistic spectrum disorders

ABSTRACT

Objectives

Inappropriate vitamin supply is a public health problem and is related to abnormalities in brain development, immune response and, more recently, in changes of gut microbial composition. It is known that low levels of vitamin in early life are linked to increased susceptibility to neurodevelopmental disorders, such as Autism Spectrum Disorders (ASD). Unfortunately, the possible peripheral influences of vitamin deficiency that leads to alterations in the gut microbiota-immune-brain axis, one important modulator of the ASD pathology, remain unclear. This narrative review discusses how the impact of vitamin deficiency results in changes in the immune regulation and in the gut microbiota composition, trying to understand how these changes may contribute for the development and severity of ASD.

Methods

The papers were selected using Pubmed and other databases. This review discusses the following topics: (1) vitamin deficiency in alterations of central nervous system in autism, (2) the impact of low levels of vitamins in immunomodulation and how it can favor imbalance in gut microbiota composition and gastrointestinal (GI) disturbances, (3) gut microbiota imbalance/inflammation associated with the ASD pathophysiology, and (4) possible evidences of the role of vitamin deficiency in dysfunctional gut microbiota-immune-brain axis in ASD.

Results

Studies indicate that hypovitaminosis A, B12, D, and K have been co-related with the ASD neuropathology. Furthermore, it was shown that low levels of these vitamins favor the Th1/Th17 environment in the gut, as well as the growth of enteropathogens linked to GI disorders.

Discussion

GI disorders and alterations in the gut microbiota-immune-brain axis seems to be linked with ASD severity. Although unclear, hypovitaminosis appears to regulate peripherally the ASD pathophysiology by modulating the gut microbiota-immune-brain axis, however, more research is still necessary to confirm this hypothesis.

KEYWORDS:

• Autism spectrum disorder
• hypovitaminosis
• gut microbiota imbalance
• inflammation

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors would like thanks the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for the financial support.

Notes on contributors

Roberta Ribeiro

Roberta Ribeiro – Bachelor in Nursing from State University of the Southwest of Bahia – UESB (2015). Master degree in Biology and Biotechnology of microorganisms from State University of Santa Cruz – UESC (2018). Since 2019, she is a Ph.D. student in Neuroscience from Federal University of Minas Gerais (UFMG). She has experience in microbiology, with emphasis on probiotics, and has interests in understanding the impact of diets in the CNS, focusing on neurodevelopmental and neurodegenerative disorders, and how the gut–brain–immune axis acts in this context.

Jacques Robert Nicoli

Jacques Robert Nicoli – Master degree in Biochemistry, Biology from the Aix-Marseille University Faculty of Sciences (1973). Ph.D. in Biochemistry and Immunology (1986) from Federal University of Minas Gerais – UFMG. Postdoctoral from the French National Institute for Agricultural Research Jouy-en-Josas (1989). Since 1986, he is a teacher/researcher at the Federal University of Minas Gerais – UFMG. He has experience in microbiology and immunology, focusing on microbial ecology, prebiotics and probiotics, and gnotobiology.

Gesivaldo Santos

Gesivaldo Santos – Bachelor in biology from State University of the Southwest of Bahia – UESB (1994). Master degree in Human Physiology from University of São Paulo – USP (2003). Ph.D. in Molecular and Functional Biology from State University of Campinas-Unicamp (2009). Since 2001, he is a teacher/researcher at the State University of the Southwest of Bahia – UESB. He has experience in Neurobiology, focusing on neurogenomics in neurodevelopmental disorders and neurodegenerative diseases.

Jane Lima-Santos

Jane Lima-Santos – Bachelor in Biology from Federal University of Viçosa-UFV (1993). Master degree in Microbiology (1997), and Ph.D. in Biochemistry and Immunology from Federal University of Minas Gerais-UFMG (2002). Postdoctoral from the department of Nuclear Engineering from the same institution (2006). Since 2008, she is a teacher/researcher at the State University of Santa Cruz – UESC. She has experience in Immunology, focusing on innate and adaptive immunology and host–pathogen interaction.