Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer's Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis

Diling Chen, Xin Yang, Jian Yang, Guoxiao Lai, Tianqiao Yong, Xiaocui Tang, Ou Shuai, Gailian Zhou, Yizhen Xie, Qingping Wu, Diling Chen, Xin Yang, Jian Yang, Guoxiao Lai, Tianqiao Yong, Xiaocui Tang, Ou Shuai, Gailian Zhou, Yizhen Xie, Qingping Wu

Abstract

Gut microbiota influences the central nervous system disorders such as Alzheimer's disease (AD). The prebiotics and probiotics can improve the host cognition. A previous study demonstrated that fructooligosaccharides from Morinda officinalis (OMO) exert effective memory improvements in AD-like animals, thereby considered as potential prebiotics; however, the underlying mechanism still remains enigma. Thus, the present study investigated whether OMO is effective in alleviating AD by targeting the microbiota-gut-brain axis. OMO was administered in rats with AD-like symptoms (D-galactose- and Aβ1-42-induced deficient rats). Significant and systematic deterioration in AD-like animals were identified, including learning and memory abilities, histological changes, production of cytokines, and microbial community shifts. Behavioral experiments demonstrated that OMO administration can ameliorate the learning and memory abilities in both AD-like animals significantly. AD parameters showed that OMO administration cannot only improve oxidative stress and inflammation disorder, but also regulate the synthesis and secretion of neurotransmitter. Histological changes indicated that OMO administration ameliorates the swelling of brain tissues, neuronal apoptosis, and down-regulation of the expression of AD intracellular markers (Tau and Aβ1-42). 16S rRNA sequencing of gut microbiota indicated that OMO administration maintains the diversity and stability of the microbial community. In addition, OMO regulated the composition and metabolism of gut microbiota in inflammatory bowel disease (IBD) mice model treated by overdosed antibiotics and thus showed the prebiotic potential. Moreover, gut microbiota plays a major role in neurodevelopment, leading to alterations in gene expression in critical brain and intestinal regions, thereby resulting in perturbation to the programming of normal cognitive behaviors. Taken together, our findings suggest that the therapeutic effect of the traditional medicine, M. officinalis, on various neurological diseases such as AD, is at least partially contributed by its naturally occurring chemical constituent, OMO, via modulating the interaction between gut ecology and brain physiology.

Keywords: Alzheimer’s disease; behavior; fructooligosaccharides; microbiota-gut-brain axis; prebiotics.

Figures

FIGURE 1
FIGURE 1
Effect of OMO in D-galactose-induced deficient rats. (A) Body weight changes during the treatments time. (B) Escape latency in the MWM. (C) Swimming time in the platform quadrant during the spatial probe test. (D) Effect on SOD, MDA, CAT, GSH-Px TchE, Ach, and Na+/K+-ATPase levels. (E) Histopathological changes in the intestine and brain. The graph Control, control group; Model, model group; OMO-50 mg, low-dose group that received D-galactose (100 mg/kg/d) by i.p. and gavage at a dosage of 50 mg/[kg⋅d] in OMO; OMO-100 mg, high-dose group that received D-galactose (100 mg/kg/d) i.p. and gavage at a dosage of 100 mg/[kg⋅d] in OMO. Values are represented as mean ± SD (n = 6) and expressed as the percentage of the control group, #p < 0.01 vs. control group, ∗p < 0.05 vs. model group, ∗∗p < 0.01 vs. model group.
FIGURE 2
FIGURE 2
Effects of OMO on gut microbiota in D-galactose-induced deficient rats. (A) Sequencing data summary at 97% similarity. (B) Results of PCA. (C) Classification and abundance of cecal contents at the phylum level. (D) Classification and abundance of cecal contents at the genus level, and the beta diversity. The graph N is normal group; M is model group; O is OMO-100 mg, high-dose group that received D-galactose (100 mg/kg/d) i.p., and gavage at a dosage of 100 mg/[kg⋅d] in OMO. Values are the means of six independent experiments (n ≥ 5).
FIGURE 3
FIGURE 3
Effect of OMO in Aβ1-42-induced deficient rats. (A) Body weight changes during the treatments time. (B-a) Escape latency in the MWM. (B-b) Swimming distance. (B-c) Swimming time in the platform quadrant during the spatial probe test. (C) Level of cytokines GM-CSF, TNF-γ, 1L-10, IL-12, 1L-17α, 1L-4, TNF-α, and VGEF-α in the serum. (D) Levels of monoamine neurotransmitters (NE, DA, 5-HT, and 5-HIAA) in the brain tissue. (E) Histopathological changes in the intestine, heart, and brain, and the expressions of Aβ1-42 and Tau proteins in brain tissues by immunohistochemistry. The graph Control, control group; Model, model group; OMO-50 mg, low-dose group that received D-galactose (100 mg/kg/d) i.p. and gavage at a dosage of 50 mg/[kg⋅d] in OMO; OMO-100 mg, high-dose group that received D-galactose (100 mg/kg/d) i.p. and gavage at a dosage of 100 mg/[kg⋅d] in OMO. Values are represented as mean ± SD (n = 6) and expressed as the percentage of the control group, #p < 0.01 vs. control group, ∗p < 0.05 vs. model group, ∗∗p < 0.01 vs. model group.
FIGURE 4
FIGURE 4
Effects of OMO on gut microbiota in Aβ1-42-induced deficient rats. (A) Rarefaction curve and (B) PCA results of different concentrations of Aβ1-42-induced groups, H (20 μg of Aβ1-42), L (20 μg of Aβ1-42), Z (normal rats with vehicle). (C) Rarefaction curve. (D) Operation schematic diagram. (E) Classification and abundance of cecal contents at the phylum level. (F) Classification and abundance of cecal contents at the genus level. (G) The dominant species classification tree. (H) The relative abundance of the dominant microorganism. Values are the means of six independent experiments.
FIGURE 5
FIGURE 5
OMO improves the pathological parameters of the high-dose broad spectrum antibiotics and TNBS-induced inflammatory bowel disease (IBD) mice. (A) Body weight changes. (B) Levels of LPS in serum. (C) The levels of cytokines (GM-CSF, TNF-γ, 1L-10, IL-12, 1L-17α, 1L-4, TNF-α, and VGEF-α) in serum. (D) The histopathological changes in colon. (E) The histopathological changes in spleen. Control is the normal group; model is the TNBS-induced group; model and high-dose antibiotics, HEP3 (100 mg/kg/d), Bifidobacterium, HEP3 and high-dose antibiotics, HEP3 and Bifidobacterium, Bifidobacterium and high-dose antibiotics, HEP3, Bifidobacterium, and high-dose antibiotics.
FIGURE 6
FIGURE 6
Immunohistochemistry staining of Foxp3 (A), IL-17 (B), NF-κB p65 (C), and TNF-α (D) in the colons of different experimental groups in high-dose broad spectrum antibiotics and TNBS-induced IBD mice after treatment with OMO.
FIGURE 7
FIGURE 7
Effects of OMO on the microbiota of cecal contents in high-dose broad spectrum antibiotics and TNBS-induced IBD mice. (A) The graph represents the rarefaction curve. (B) The dominant species classification tree. (C) The classification and abundance of cecal contents at the phylum level. (D) The classification and abundance of cecal contents at the family level. Values are the means of six independent experiments.
FIGURE 8
FIGURE 8
Effects of Aβ1-42 on gut microbiota in rats. (A–F) The rarefaction curve of different concentrations and durations in Aβ1-42-induced groups, H (20 μg of Aβ1-42), L (20 μg of Aβ1-42), Z (normal rats with vehicle); H1, H2, and H3 (or L1, L2, L3) is the treatment time after injection of Aβ1-42 at 2nd, 3rd, and 4th weeks; (G) is the dominant species classification tree; (H) is the relative abundance of the dominant microorganism. Values represent the means of six independent experiments.
FIGURE 9
FIGURE 9
The KEGG pathway enrichment of gut microbiota in the metabolism system. (A) The dynamic variations in the 2nd, 3rd, and 4th week after injection of Aβ1-42 in rats. (B) The 4th week after injection of Aβ1-42 in rats. (C) The high dose broad spectrum antibiotics and TNBS-induced IBD mice.
FIGURE 10
FIGURE 10
Small intestine transcriptome analysis in the deficit rats by injected Aβ1-42. (A) The statistics of transcriptome sequences. (B) DEGs in the small intestine at different concentrations of Aβ1-42. (C) Venn diagram of DEGs. (D) The heat map of the relative expressions of DEGs in all three groups.
FIGURE 11
FIGURE 11
The KEGG pathway enrichment of DEGs in the small intestine transcriptome in deficient rats induced by Aβ1-42. (A) The group of Aβ-10 vs. the Normal; (B) the group of Aβ-20 vs. the Normal; (C) the group of Aβ-20 vs. the Aβ-10.
FIGURE 12
FIGURE 12
Brain transcriptome analysis in the deficit rats by injected Aβ1-42. (A) Statistics of the transcriptome sequences. (B) The differentially expressed genes in the brain at different concentration of Aβ1-42. (C) Venn diagram of DEGs. (D) The heat map of the relative expressions of DEGs in all the three groups.
FIGURE 13
FIGURE 13
The KEGG pathway enrichment of DEGs in brain transcriptome in the deficit rats induced by Aβ1-42. (A) The group of Aβ-10 vs. the Normal; (B) the group of Aβ-20 vs. the Normal; (C) the group of Aβ-20 vs. the Aβ-10.
FIGURE 14
FIGURE 14
Binding pattern of fructooligosaccharides from Morinda officinalis: (A) HPLC-ELSD analysis of fructooligosaccharides from M. officinalis. (B) The chemical structure of nystose (3), F-fructofuranose nystose (4), fructooligosaccharide (GF5, 5), fructooligosaccharide (GF6, 6); (C) The docked poses were ranked by CDOCKER- ENERGY and the top 10 poses with the co-crystal ligand for SusCD were retained. The data revealed compounds 3, 4, 5, and 6 with CDOCKER-ENERGY of –52.0244180, –75.5881, –101.88, and –110.387, respectively.
FIGURE 15
FIGURE 15
The interactive information analysis of DEGs in brain and intestine in deficient rats by injected Aβ1-42. (A–C) Wayne chart of DEGs in the brain and intestine transcriptome. (D–F) KEGG pathway enrichment of DEGs in the brain and intestine transcriptome.

References

    1. Abbott A. (2011). Dementia: a problem for our age. Nature 475 S2–S4. 10.1038/475S2a
    1. Akbari E., Asemi Z., Daneshvar Kakhaki R., Bahmani F., Kouchaki E., Tamtaji O. R., et al. (2016). Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer’s disease: a randomized, double-blind and controlled trial. Front. Aging Neurosci. 8:256. 10.3389/fnagi.2016.00256
    1. Alkasir R., Li J., Li X., Jin M., Zhu B. (2017). Human gut microbiota: the links with dementia development. Protein Cell. 8 90–102. 10.1007/s13238-016-0338-6
    1. Allen A. P., Hutch W., Borre Y. E., Kennedy P. J., Temko A., Boylan G., et al. (2016). Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl. Psychiatry 6:e939. 10.1038/tp.2016.191
    1. Anderson G., Seo M., Berk M., Carvalho A. F., Maes M. (2016). Gut permeability and microbiota in Parkinson’s disease: role of depression, tryptophan catabolites, oxidative and nitrosative stress and melatonergic pathways. Curr. Pharm. Des. 22 6142–6151. 10.2174/1381612822666160906161513
    1. Arboleya S., Sanchez B., Milani C., Duranti S., Solis G., Fernandez N., et al. (2015). Intestinal microbiota development in preterm neonates and effect of perinatal antibiotics. J. Pediatr. 166 538–544. 10.1016/j.jpeds.2014.09.041
    1. Benjamin J. L., Hedin C. R., Koutsoumpas A., Ng S. C., McCarthy N. E., Hart A. L., et al. (2011). Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn’s disease. Gut 60 923–929. 10.1136/gut.2010.232025
    1. Bland J. (2016). Intestinal microbiome, Akkermansia muciniphila, and medical nutrition therapy. Integr. Med. 15 14–16.
    1. Burokas A., Arboleya S., Moloney R. D., Peterson V. L., Murphy K., Clarke G., et al. (2017). Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol. Psychiatry 82 472–487. 10.1016/j.biopsych.2016.12.031
    1. Cabili M. N., Trapnell C., Goff L., Koziol M., Tazon-Vega B., Regev A., et al. (2011). Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 25 1915–1927. 10.1101/gad.17446611
    1. Cai B., Cui C. B., Chen Y. H., Luo Z. P., Yang M., Yao Z. W. (1996). Antidepressant effect of inulin- type oligosaccharides from Morinda officinalis How in mice. Chin. J. Pharmacol. Toxicol. 10 109–112.
    1. Chen D. L., Li N., Lin L., Long H. M., Lin H., Chen J., et al. (2014a). Confocal mirco-Raman spectroscopic analysis of the antioxidant protection mechanism of the oligosaccharides extracted from Morinda officinalis on human sperm DNA. J. Ethnopharmacol. 153 119–124. 10.1016/j.jep.2014.01.021
    1. Chen D. L., Yong T. Q., Yang J., Zheng C. Q., Shuai O., Xie Y. Z. (2017). Docking studies and biological evaluation of a potential β-secretase inhibitor of 3-hydroxyhericenone F from Hericium erinaceus. Front. Pharmacol. 8:219 10.3389/fphar.2017.00219
    1. Chen D. L., Zhang P., Lin L., Shuai O., Zhang H. M., Liu S. H., et al. (2013). Protective effect of Bajijiasu against β-amyloid-induced neurotoxicity in PC12 cells. Cell Mol. Neurobiol. 33 837–850. 10.1007/s10571-013-9950-7
    1. Chen D. L., Zhang P., Lin L., Zhang H. M., Deng S. D., Wu Z. Q., et al. (2014b). Protective effects of bajijiasu in a rat model of Aβ25-35-induced neurotoxicity. J. Ethnopharmacol. 154 206–217. 10.1016/j.jep.2014.04.004
    1. Choi Y. J., Yang H. S., Jo J. H., Lee S. C., Park T. Y., Choi B. S., et al. (2015). Anti-amnesic effect of fermented Ganoderma lucidum water extracts by lactic acid bacteria on scopolamine-induced memory impairment in rats. Prev. Nutr. Food Sci. 20 126–132. 10.3746/pnf.2015.20.2.126
    1. Davis D. J., Doerr H. M., Grzelak A. K., Busi S. B., Jasarevic E., Ericsson A. C., et al. (2016). Lactobacillus plantarum attenuates anxiety-related behavior and protects against stress-induced dysbiosis in adult zebrafish. Sci. Rep. 6:33726. 10.1038/srep33726
    1. Derrien M., Belzer C., de Vos W. M. (2016). Akkermansia muciniphila and its role in regulating host functions. Microb. Pathog. 106 171–181. 10.1016/j.micpath.2016.02.005
    1. Dinan T. G., Cryan J. F. (2017). The microbiome-gut-brain axis in health and disease. Gastroenterol. Clin. North Am. 46 77–89. 10.1016/j.gtc.2016.09.007
    1. Erdman S. E., Poutahidis T. (2016). Microbes and oxytocin: benefits for host physiology and behavior. Int. Rev. Neurobiol. 131 91–126. 10.1016/bs.irn.2016.07.004
    1. Gao J., Zhou R., You X., Luo F., He H., Chang X., et al. (2016). Salidroside suppresses inflammation in a D-galactose-induced rat model of Alzheimer’s disease via SIRT1/NF-κB pathway. Metab. Brain Dis. 31 771–778. 10.1007/s11011-016-9813-2
    1. Garcia-Mazcorro J. F., Barcenas-Walls J. R., Suchodolski J. S., Steiner J. M. (2017). Molecular assessment of the fecal microbiota in healthy cats and dogs before and during supplementation with fructo-oligosaccharides (FOS) and inulin using high-throughput 454-pyrosequencing. PeerJ 5:e3184. 10.7717/peerj.3184
    1. Gareau M. G. (2014). Microbiota-gut-brain axis and cognitive function. Adv. Exp. Med. Biol. 817 357–371. 10.1007/978-1-4939-0897-4_16
    1. Glenwright A. J., Pothula K. R., Bhamidimarri S. P., Chorev D. S., Baslé A., Firbank S. J., et al. (2017). Structural basis for nutrient acquisition by dominant members of the human gut microbiota. Nature 541 407–411. 10.1038/nature20828
    1. Greer R. L., Dong X., Moraes A. C., Zielke R. A., Fernandes G. R., Peremyslova E., et al. (2016). Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism. Nat. Commun. 7:13329. 10.1038/ncomms13329
    1. Harach T., Marungruang N., Duthilleul N., Cheatham V., Mc Coy K. D., Frisoni G., et al. (2017). Reduction of Abeta amyloid pathology in APP/PS1 transgenic mice in the absence of gut microbiota. Sci. Rep. 7:41802. 10.1038/srep41802
    1. Henning S. M., Summanen P. H., Lee R. P., Yang J., Finegold S. M., Heber D., et al. (2017). Pomegranate ellagitannins stimulate the growth of Akkermansia muciniphila in vivo. Anaerobe 43 56–60. 10.1016/j.anaerobe.2016.12.003
    1. Hsiao E. Y., McBride S. W., Hsien S., Sharon G., Hyde E. R., McCue T., et al. (2013). Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155 1451–1463. 10.1016/j.cell.2013.11.024
    1. Hu X., Wang T., Jin F. (2016). Alzheimer’s disease and gut microbiota. Sci. China Life Sci. 59 1006–1023. 10.1007/s11427-016-5083-9
    1. Huang H. C., Zheng B. W., Guo Y., Zhao J., Zhao J. Y., Ma X. W., et al. (2016). Antioxidative and neuroprotective effects of curcumin in an Alzheimer’s disease rat model co-treated with intracerebroventricular streptozotocin and subcutaneous D-galactose. J. Alzheimers Dis. 52 899–911. 10.3233/JAD-150872
    1. Jeong J. J., Woo J. Y., Kim K. A., Han M. J., Kim D. H. (2015). Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent memory impairment in Fischer 344 rats. Lett. Appl. Microbiol. 60 307–314. 10.1111/lam.12393
    1. Jiang C., Li G., Huang P., Liu Z., Zhao B. (2017). The gut microbiota and Alzheimer’s disease. J. Alzheimers Dis. 58 1–15. 10.3233/JAD-161141
    1. Jung I. H., Jung M. A., Kim E. J., Han M. J., Kim D. H. (2012). Lactobacillus pentosus var. plantarum C29 protects scopolamine-induced memory deficit in mice. J. Appl. Microbiol. 113 1498–1506. 10.1111/j.1365-2672.2012.05437.x
    1. Le Sage F., Meilhac O., Gonthier M. P. (2017). Porphyromonas gingivalis lipopolysaccharide induces pro-inflammatory adipokine secretion and oxidative stress by regulating Toll-like receptor-mediated signaling pathways and redox enzymes in adipocytes. Mol. Cell. Endocrinol. 446 102–110. 10.1016/j.mce.2017.02.022
    1. Leung K., Thuret S. (2015). Gut microbiota: a modulator of brain plasticity and cognitive function in ageing. Healthcare 3 898–916. 10.3390/healthcare3040898
    1. Li X., Lu F., Li W., Xu J., Sun X. J., Qin L. Z., et al. (2016). Minocycline ameliorates D-galactose- induced memory deficits and loss of Arc/Arg3.1 expression. Mol. Biol. Rep. 43 1157–1163. 10.1007/s11033-016-4051-6
    1. Li Y. F., Liu Y. Q., Yang M., Wang H. L., Huang W. C., Zhao Y. M., et al. (2004). The cytoprotective effect of inulin-type hexasaccharide extracted from Morinda officinalis on PC12 cells against the lesion induced by corticosterone. Life Sci. 75 1531–1538. 10.1016/j.lfs.2004.02.029
    1. Li Y. F., Yuan L., Xu Y. K., Yang M., Zhao Y. M., Luo Z. P. (2001). Antistress effect of oligosaccharides extracted from Morinda officinalis in mice and rats. Acta Pharmacol. Sin. 22 1084–1088.
    1. Liang C. Y., Liang Y. M., Liu H. Z., Zhu D. M., Hou S. Z., Wu Y. Y., et al. (2017). Effect of Dendrobium officinale on D-galactose-induced aging mice. Chin. J. Integr. Med. 10.1007/s11655-016-2631-x [Epub ahead of print].
    1. Ling Z. X., Xia L., Jia X. Y., Cheng Y. W., Luo Y. Q., Li Y., et al. (2014). Impacts of infection with different toxigenic Clostridium difficile strains on faecal microbiota in children. Sci. Rep. 4:7485. 10.1038/srep07485
    1. Liu K. L., He Y. G., Yu L. X., Chen Y., He R. (2017). Elevated formaldehyde in the cecum of APP/PS1 mouse. Microbiol. China 44 1761–1766.
    1. Malaguarnera M., Vacante M., Antic T., Giordano M., Chisari G., Acquaviva R., et al. (2012). Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis. Dig. Dis. Sci. 57 545–553. 10.1007/s10620-011-1887-4
    1. Mayer E. A., Knight R., Mazmanian S. K., Cryan J. F., Tillisch K. (2014). Gut microbes and the brain: paradigm shift in neuroscience. J. Neurosci. 34 15490–15496. 10.1523/JNEUROSCI.3299-14.2014
    1. Minter M. R., Zhang C., Leone V., Ringus D. L., Zhang X., Oyler-Castrillo P., et al. (2016). Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease. Sci. Rep. 6:30028. 10.1038/srep30028
    1. Park K. Y., Jeong J. K., Lee Y. E., Daily J. W., III (2014). Health benefits of kimchi (Korean fermented vegetables) as a probiotic food. J. Med. Food 17 6–20. 10.1089/jmf.2013.3083
    1. Petra A. I., Panagiotidou S., Hatziagelaki E., Stewart J. M., Conti P., Theoharides T. C. (2015). Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin. Ther. 37 984–995. 10.1016/j.clinthera.2015.04.002
    1. Pistollato F., Sumalla Cano S., Elio I., Masias Vergara M., Giampieri F., Battino M. (2016). Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutr. Rev. 74 624–634. 10.1093/nutrit/nuw023
    1. Potgieter M., Bester J., Kell D. B., Pretorius E. (2015). The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol. Rev. 39 567–591. 10.1093/femsre/fuv013
    1. Rhee S. H., Pothoulakis C., Mayer E. A. (2009). Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol. 6 306–314. 10.1038/nrgastro.2009.35
    1. Rieder R., Wisniewski P. J., Alderman B. L., Campbell S. C. (2017). Microbes and mental health: a review. Brain Behav. Immun. 66 9–17. 10.1016/j.bbi.2017.01.016
    1. Rigo-Adrover M., Pérez-Berezo T., Ramos-Romero S., van Limpt K., Knipping K., Garssen J., et al. (2017). A fermented milk concentrate and a combination of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides/pectin-derived acidic oligosaccharides protect suckling rats from rotavirus gastroenteritis. Br. J. Nutr. 117 209–217. 10.1017/S0007114516004566
    1. Russo R., Cristiano C., Avagliano C., De Caro C., La Rana G., Raso G. M., et al. (2017). Gut-brain axis: role of lipids in the regulation of inflammation, pain and CNS diseases. Curr. Med. Chem. 10.2174/0929867324666170216113756 [Epub ahead of print].
    1. Sanches Lopes S. M., Francisco M. G., Higashi B., de Almeida R. T., Krausová G., Pilau E. al. (2016). Chemical characterization and prebiotic activity of fructo-oligosaccharides from Stevia rebaudiana (Bertoni) roots and in vitro adventitious root cultures. Carbohydr. Polym. 152 718–725. 10.1016/j.carbpol.2016.07.043
    1. Scott K. A., Ida M., Peterson V. L., Prenderville J. A., Moloney G. M., Izumo T., et al. (2017). Revisiting Metchnikoff: age-related alterations in microbiota-gut-brain axis in the mouse. Brain Behav Immun. 65 20–32. 10.1016/j.bbi.2017.02.004
    1. Servin A. L. (2004). Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol. Rev. 28 405–440. 10.1016/j.femsre.2004.01.003
    1. Sun L., Luo H., Bu D., Zhao G., Yu K., Zhang C., et al. (2013). Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts. Nucleic Acids Res. 41:e166. 10.1093/nar/gkt646
    1. Tan B. X., Chen C. F., Chen J. W., Su W., Li X. Y., Lin R. S., et al. (2000a). Mechanism of BA-JI-SU in invigorating kidney to anti-aging. J. New Chin. Med. 32 36–38.
    1. Tan B. X., Su W., Chen J. W., Chen C. F., Wang Y., Li X. Y. (2000b). improvement effect of bajiasu on spatial learning and memory ability of rats. Tradit. Chin. Drugs Res. Clin. Pharmacol. 11 95–97.
    1. Tanner S. A., Lacroix C., Del’Homme C., Jans C., Zihler Berner A., Bernalier-Donadille A., et al. (2015). Effect of Bifidobacterium thermophilum RBL67 and fructo-oligosaccharides on the gut microbiota in Göttingen minipigs. Br. J. Nutr. 114 746–755. 10.1017/S0007114515002263
    1. Trapnell C., Hendrickson D. G., Sauvageau M., Goff L., Rinn J. L., Pachter L. (2013). Differential analysis of gene regulation at transcript resolution with RNA-seq. Nat. Biotechnol. 31 46–53. 10.1038/nbt.2450
    1. Valdés-Varela L., Ruas-Madiedo P., Gueimonde M. (2017). In vitro fermentation of different fructo-oligosaccharides by Bifidobacterium strains for the selection of synbiotic combinations. Int. J. Food Microbiol. 242 19–23. 10.1016/j.ijfoodmicro.2016.11.011
    1. Van Herreweghen F., Van den Abbeele P., De Mulder T., De Weirdt R., Geirnaert A., Hernandez-Sanabria E., et al. (2017). In vitro colonisation of the distal colon by Akkermansia muciniphila is largely mucin and pH dependent. Benef. Microbes 8 81–96. 10.3920/BM2016.0013
    1. Vandenplas Y., Ludwig T., Bouritius H., Alliet P., Forde D., Peeters S., et al. (2017). Randomised controlled trial demonstrates that fermented infant formula with short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides reduces the incidence of infantile colic. Acta Paediatr. 106 1150–1158. 10.1111/apa.13844
    1. Vanegas S. M., Meydani M., Barnett J. B., Goldin B., Kane A., Rasmussen H., et al. (2017). Substituting whole grains for refined grains in a 6-wk randomized trial has a modest effect on gut microbiota and immune and inflammatory markers of healthy adults. Am. J. Clin. Nutr. 105 635–650. 10.3945/ajcn.116.146928
    1. Vuong H. E., Yano J. M., Fung T. C., Hsiao E. Y. (2017). The microbiome and host behavior. Annu. Rev. Neurosci. 40 21–49. 10.1146/annurev-neuro-072116-031347
    1. Wall R., Cryan J. F., Ross R. P., Fitzgerald G. F., Dinan T. G., Stanton C. (2014). Bacterial neuroactive compounds produced by psychobiotics. Adv. Exp. Med. Biol. 817 221–239. 10.1007/978-1-4939-0897-4_10
    1. Wang L., Feng Z., Wang X., Wang X., Zhang X. (2010). DEGseq: an R package for identifying differentially expressed genes from RNA-seq data. Bioinformatics 26 136–138. 10.1093/bioinformatics/btp612
    1. Wang X., Li G. J., Hu H. X., Ma C., Ma D. H., Liu X. L., et al. (2016). Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats. Transl. Neurosci. 7 151–157. 10.1515/tnsci-2016-0022
    1. Wei Y., Lu C., Chen J., Cui G., Wang L., Yu T., et al. (2017). High salt diet stimulates gut Th17 response and exacerbates TNBS-induced colitis in mice. Oncotarget 8 70–82. 10.18632/oncotarget.13783
    1. Woo J. Y., Gu W., Kim K. A., Jang S. E., Han M. J., Kim D. H. (2014). Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model. Anaerobe 27 22–26. 10.1016/j.anaerobe.2014.03.003
    1. Yano J. M., Yu K., Donaldson G. P., Shastri G. G., Ann P., Ma L., et al. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161 264–276. 10.1016/j.cell.2015.02.047
    1. Zeng G. F., Zhang Z. Y., Lu L., Xiao D. Q., Zong S. H., He J. M. (2013). Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats. Rejuvenation Res. 16 124–133. 10.1089/rej.2012.1389
    1. Zhan P. Y., Peng C. X., Zhang L. H. (2014). Berberine rescues D-galactose-induced synaptic/memory impairment by regulating the levels of Arc. Pharmacol. Biochem. Behav. 117 47–51. 10.1016/j.pbb.2013.12.006
    1. Zhong L., Huang F., Shi H., Wu H., Zhang B., Wu X., et al. (2016). Qing’E formula alleviates the aging process in D-galactose-induced aging mice. Biomed. Rep. 5 101–106. 10.3892/br.2016.667

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera