A Combination Supplement of Fructo- and Xylo-Oligosaccharides Significantly Abrogates Oxidative Impairments and Neurotoxicity in Maternal/Fetal Milieu Following Gestational Exposure to Acrylamide in Rat

Abstract

Prebiotic oligosaccharides are demonstrated to confer a wide spectrum of physiological benefits during pregnancy. In view of this, focused attempts are being directed towards understanding their role as modulators of brain chemistry and behavior. Epidemiological studies have identified that exposure to neurotoxins during prenatal/early life can profoundly impact neurodevelopment/function. In this context, we have tested the hypothesis that a combination of prebiotic supplements during gestation has the propensity to attenuate acrylamide (ACR) induced oxidative impairments, mitochondrial dysfunction and neurotoxicity in maternal and fetal brain of rats. To achieve this, pregnant dams given oral supplements of a combination of fructo- and xylooligosaccharides (FOS + XOS, 3 g/kg/day) during gestation days (GD 0-19) were exposed to ACR (200 ppm in drinking water, GD 6-19). The behavioral analysis revealed that ACR dams fed prebiotics displayed higher exploratory behavior in the open field test. The prenatal evaluation showed that ACR-induced decrements of placental/fetal weights were markedly restored with prebiotic feeding. Prebiotics significantly offset markers of oxidative stress, restored enzymic antioxidants, cholinergic and mitochondrial function in the maternal and fetal brain. Concomitantly, prebiotics restored ACR-induced depletion in the levels of dopamine and γ-aminobutyric acid in the maternal cortex that positively correlated with cecal bacterial numbers. Collectively, these data suggest that prenatal prebiotic oligosaccharide supplements protect developing brain against oxidative stress-mediated neurotoxicity. While the underlying mechanism/s by which prebiotics abrogate the impact of neurotoxicants in the developing brain merits further studies, we speculate that it may be mediated predominantly through attenuation of oxidative stress and proliferation of enteric microbiota.

Prebiotics Regulation of Intestinal Microbiota Attenuates Cognitive Dysfunction Induced by Surgery Stimulation in APP/PS1 Mice

“…In summary, the typical changed intestinal taxa after surgery also play roles in the neurodegeneration diseases and immune diseases, indicating that intestinal microbiota alterations are the potential mechanism for the intestinal barrier damage and inflammatory response, as well as cognitive dysfunction after surgery. When compared with other well stablished prebiotics, such as inulin or FOS, XOS showed higher resistance to digestion and has been reported to present many beneficial functions including preventing intestinal microbiota alteration, neurotoxicity and intestinal inflammation [41,42]. The present study indicates that XOS intervention attenuated surgery induced intestinal microbiota alterations, including four upregulated and two downregulated taxa, then Muribaculum and Lactobacillus were also upregulated by XOS intervention after surgery.…”

“…When compared with other well stablished prebiotics, such as inulin or FOS, XOS showed higher resistance to digestion and has been reported to present many beneficial functions including preventing intestinal microbiota alteration, neurotoxicity and intestinal inflammation [ 41 , 42 ]. The present study indicates that XOS intervention attenuated surgery induced intestinal microbiota alterations, including four upregulated and two downregulated taxa, then Muribaculum and Lactobacillus were also upregulated by XOS intervention after surgery.…”

Emerging literature in the Microbiota-Brain Axis and Perinatal Mood and Anxiety Disorders

“…There is evidence that prebiotic consumption may impact the effect of stressors on maternal outcomes. In open field mouse experiments, dams exposed to Acrylamide (ACR, a known neurotoxin) displayed increased anxiety-like behavior compared to control dams, while supplementation with prebiotics (fructo- and xylo-oligosaccharide, non-digestible carbohydrates that are easily fermented by intestinal organisms) restored exploratory behavior in ACR-exposed dams, indicative of reduced anxiety (Krishna et al, 2015). ACR-exposed dams also supplemented with prebiotics showed a reduction in markers of oxidative stress and a recovery of antioxidant enzymes in the maternal brain to control levels.…”

Targeted Approaches for In Situ Gut Microbiome Manipulation

“…Decreased levels of Bifidobacterium have been observed and associated with obesity and Type II diabetes, while supplementation of NDC in murine models [ 18 ] and human subjects [ 19 , 20 ] has been found to restore those levels. The major end-products of NDC fermentation are short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate [ 21 , 22 , 23 , 24 ]. Acetate and propionate are involved in gluconeogenesis in hepatocytes and act as signalling molecules [ 25 ], while butyrate is an important carbon source for epithelial cells in the colon [ 26 ].…”