Maternal Iron Deficiency Programs Offspring Cognition and Its Relationship with Gastrointestinal Microbiota and Metabolites

• Main Authors: Hsin-Yi Hsieh, Yu-Chieh Chen, Mei-Hsin Hsu, Hong-Ren Yu, Chung-Hao Su, You-Lin Tain, Li-Tung Huang, Jiunn-Ming Sheen
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: spatial deficit; iron deficiency; microbiota; programming
• Online Access: https://www.mdpi.com/1660-4601/17/17/6070
• ISSN: 1661-7827; 1660-4601

Iron is an essential micronutrient for the brain development of the fetus. Altered intestinal microbiota might affect behavior and cognition through the so-called microbiota-gut-brain axis. We used a Sprague-Dawley rat model of a maternal low-iron diet to explore the changes in cognition, dorsal hippocampal brain-derived neurotrophic factor (BDNF) and related pathways, gut microbiota, and related metabolites in adult male offspring. We established maternal iron-deficient rats by feeding them a low-iron diet (2.9 mg/kg), while the control rats were fed a standard diet (52.3 mg/kg). We used a Morris water maze test to assess spatial learning and long-term memory. Western blot (WB) assays and a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect the BDNF concentration and related signaling pathways. We collected fecal samples for microbiota profiling and measured the concentrations of plasma short-chain fatty acids. The adult male offspring of maternal rats fed low-iron diets before pregnancy, during pregnancy and throughout the lactation period had (1) spatial deficits, (2) a decreased BDNF mRNA expression and protein concentrations, accompanied by a decreased TrkB protein abundance, (3) a decreased plasma acetate concentration, and (4) an enrichment of the <i>Bacteroidaceae</i> genus <i>Bacteroides</i> and <i>Lachnospiraceae</i> genus <i>Marvinbryantia</i>. Maternal iron deficiency leads to an offspring spatial deficit and is associated with alternations in gastrointestinal microbiota and metabolites.