Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression

Wang, Xinyi; Sun, Guangqiang; Feng, Teng; Zhang, Jing; Huang, Xun; Wang, Tao; Xie, Zuoquan; Chu, Xingkun; Yang, Jun; Wang, Huan; Chang, Shuaishuai; Gong, Yanxue; Ruan, Lingfei; Zhang, Guanqun; Yan, Siyuan; Wen, Li-Li; Du, Chen; Yang, Da; Zhang, Qingli; Lin, Feifei; Liu, Jia; Zhang, Haiyan; Ge, Changrong; Xiao, Shifu; Ding, Jian; Geng, Meiyu

doi:10.1038/s41422-019-0216-x

Cited by 809 publications

(653 citation statements)

References 61 publications

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“…A recent investigation has shown that GV-971, a sodium oligomannate, produced an evident and consistent improvement of cognition in phase 3 clinical trial in China. GV-971(degree of polymerization: 2-10, molecular weight: up to 1kDa, quantities ingested: 100 mg/kg/day, oral administration) suppressed gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnessed neuroinflammation, and reversed the cognition impairment in mild-to-moderate AD patients [103]. All these findings offered the possibility of a conceptual advancement in the understanding of the etiology of AD.…”

Section: Neuroprotective Activitymentioning

confidence: 91%

“…Future studies identifying the crucial strains of bacteria accounting for the effects of pM on metabolic and neuroinflammation changes will be critical. In addition, extensive research will be required to identify other mechanistic links connecting gut microbiota and neuroinflammation [20,103], and uncover other possible effects of AOS on intestinal microbes.…”

Section: Neuroprotective Activitymentioning

confidence: 99%

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Advances in Research on the Bioactivity of Alginate Oligosaccharides

et al. 2020

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Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products.2 of 26 the 4 C 1 conformation and are linked by β-1,4-glycosidic bond, while in pG, all G residues are in the 1 C 4 conformation and are linked by an α-1,4-glycosidic bond. These features are responsible for the differences in their higher-order structure. For example, pG exhibits an egg-box-like conformation and usually forms stiffer 2-fold screw helical chains when dissolved in water, while pM forms belt chains through intra-molecular hydrogen bonds. Due to these dissimilarities, pM and pG, as well as their derivatives, will exhibit different activities [12].As the most abundant marine biomass and low-cost material, alginate has been extensively used in the food and medical industries. The widespread utilization is also driven by its favorable chemical properties and versatile activities. However, the applications of alginate have been greatly limited due to its high molecular weight and low bioavailability. Therefore, the degradation of high molecular weight polysaccharides into low molecular weight poly-or oligosaccharides is considered of great significance for improving their bioavailability, increasing the body's absorption of drugs, and fully utilizing the efficacy of polysaccharides. Recently, the degradation products of alginate, i.e., alginate oligosaccharides (AOS), have attracted increasing attention due to their biological activities and excellent solubility in water [13]. AOS can be depolymerized by different degradation methods, including enzymatic degradation, acid hydrolysis, and oxidative degradation [14]. Alginate lyases have been isolated from a wide range of organisms, including algae, marine invertebrates, and marine and terrestrial microorganisms, which can degrade alginate into unsaturated oligosaccharides by β-elimination [15,16]. Moreover, due to differences in degradation patterns, G content (G/M ratio), molecular weight, and spatial conformation of degradation products, AOS possess a variety of biological activities. They have anti-tumor properties [17], counteract oxidation [8], regulate immune respo...

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Section: Neuroprotective Activitymentioning

confidence: 91%

Section: Neuroprotective Activitymentioning

confidence: 99%

Advances in Research on the Bioactivity of Alginate Oligosaccharides

et al. 2020

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“…The identified protein lists were generated with a target-decoy strategy based on a FDR cut-off of 0.01. Label-free quantification (LFQ) intensity of proteins across all samples were obtained with the MaxLFQ algorithm 17 . Taxonomic and functional enrichment analysis was performed using the enrichment module on iMetalab.ca 40 through inputting the list of altered proteins groups.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have added drug stimulation to the in vitro gut bacteria at various points during the growth phases of the gut microbiome. For example, Maier et al 16 , Li et al 15 and Wang et al 17 studied microbial responses to drugs by inoculating bacterial strains or fecal inoculum into culture mediums containing drugs. Wu et al 10 used the SHRIM to explore the effect of metformin on a stabilized gut microbial community in vitro, and added the metformin after one week of stabilization in SHRIM.…”

Section: Introductionmentioning

confidence: 99%

Growth phase-dependent responses of an in vitro gut microbiome to metformin

Zhang

Ning

et al. 2020

Preprint

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In vitro gut microbiota models are often used to study drug-microbiome interaction. Similar to culturing individual microbial strains, the biomass accumulation of in vitro gut microbiota follows a logistic growth curve. Current studies on in vitro gut microbiome responses introduce drug stimulation during different growth stages, e.g. lag phase or stationary phase. However, in vitro gut microbiota in different growth phases may respond differently to same stimuli. Therefore, in this study, we used a 96-deep well plate-based culturing model (MiPro) to culture the human gut microbiota. Metformin, as the stimulus, was added at the lag, log and stationary phases of growth. Microbiome samples were collected at different time points for optical density and metaproteomic functional analysis. Results show that in vitro gut microbiota responded differently to metformin added during different growth phases, in terms of the growth curve, alterations of taxonomic and functional compositions. The addition of drugs at log phase leads to the greatest decline of bacterial growth. Metaproteomic analysis suggested that the strength of the metformin effect on the gut microbiome functional profile was ranked as lag phase > log phase > stationary phase. Our results showed that metformin added at lag phase resulted in a significantly reduced abundance of the Clostridiales order as well as an increased abundance of the Bacteroides genus, which was different from stimulation during the rest of the growth phase.Metformin also resulted in alterations of several pathways, including energy production and conversion, lipid transport and metabolism, translation, ribosomal structure and biogenesis. Our results indicate that the timing for drug stimulation should be considered when studying drugmicrobiome interactions in vitro.

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“…Researchers are now convinced that gut bacteria may be involved in many neurological disorders including AD. The oligomannate discovery opens the door widely to address many other diseases via targeting the microbiome [15].…”

Section: Highlighted By Rafik Karamanmentioning

confidence: 99%