Available online 5 April 2024, 109640

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Midlife overweight and obesity are risk factors of cognitive decline and Alzheimer' s disease (AD) in late life. In addition to increase the risk of obesity and cognitive dysfunction, diets rich in fats also contributes to an imbalance of gut microbiota. Xylo-oligosaccharides (XOS) are a kind of prebiotics with several biological advantages, and can selectively promote the growth of beneficial microorganism in the gut. To explore whether XOS can alleviate cognitive decline induced by high-fat diet (HFD) through improving gut microbiota composition, mice were fed with normal control or 60% HFD for 9 weeks to induce obesity. After that, mice were supplemented with XOS (30 g or 60 g/kg-diet) or without, respectively, for 12 weeks. The results showed that XOS inhibited weight gain, decreased epidydimal fat weight, and improved fasting blood sugar and blood lipids in mice. Additionally, XOS elevated spatial learning and memory function, decreased amyloid plaques accumulation, increased brain-derived neurotrophic factor levels, and improved neuroinflammation status in hippocampus. Changes in glycerolipids metabolism-associated lipid compounds caused by HFD in hippocampus were reversed after XOS intervention. On the other hand, after XOS intervention, increase in immune-mediated bacteria, Faecalibacterium was observed. In conclusion, XOS improved gut dysbiosis and ameliorated spatial learning and memory dysfunction caused by HFD by decreasing cognitive decline-associated biomarkers and changing lipid composition in hippocampus.

Section snippetsINTRODUCTION

The prevalence of obesity is increasing worldwide [1]. Obesity is a risk factor for multiple diseases, such as type II diabetes mellitus (T2DM), cardiovascular diseases (CVD), several types of cancer, and cognitive impairment [2]. Diets rich in fats increase the risks of obesity and conditions involving cognitive impairment, such as Alzheimer's disease (AD) [3,4]. In experiments that involved feeding high-fat diets (HFDs) to rodents, the identified markers of cognitive decline included defects

Animals and study design

Fig. 1 shows the experiment procedure. Male C57BL/6 mice (25 weeks old) were obtained from the National Laboratory Animal Center (Taipei, Taiwan) and housed under laboratory conditions with a 12:12 light–dark cycle (temperature, 23 ± 2°C; humidity, 50%–60%) and ad libitum access to food and fresh water. After the mice underwent acclimatization for 3 weeks (baseline), they were randomly divided into a normal control (NC) group (n = 24) or a HFD group (n = 24). After 9 weeks, the mice were

RESULTS

At baseline (mice 25 wk old), no significant difference in body weight was identified between the NC and HFD groups. After 9 weeks (mice wk 37 old) of consuming high fat diet, the mean body weight in the HFD was significantly higher than that in the NC mice (p < 0.05). The food intake and energy intake in the HFD mice were significantly lower than those in the NC mice (p < 0.05). The food efficiency ratio (FER) in the HFD group was significantly higher than that in the NC group (p < 0.01; Table

DISCUSSION

This study was to explore the effects and mechanism of low or high doses of xylo-oligosaccharide on cognitive decline in mice induced by a high-fat diet. In the present study, the body weight in the HFD mice significantly increased. However, the food and energy consumption significantly decreased during the 21-week HFD intervention. A similar result was also reported that the food intake of rats fed an HFD significantly decreased, whereas their body weight and obesity level significantly

CONCLUSION

In our study, we found that a diet high in fat in fat reduced weigh of hippocampus, induced AD-related Aß, decreased expression of brain-derived neurotrophic factor, and increased the BBB leakage marker ZO-1, while the content of lipid compounds related to glycerolipid and glycerophospholipid metabolism was altered in the hippocampus. A 12-week XOS intervention led to changes in the gut microbiota composition and a significant increase in the abundance of beneficial bacteria in the mice fed a

Author Statement

We have revised the manuscript and increased the resolution of the figures carefully according to the reviewer's comments. This manuscript is solely submitted to the Journal of Nutritional Biochemistry.

CRediT authorship contribution statement

Chu-Yun Teng: Writing – original draft, Methodology, Formal analysis, Data curation. Ning-Jo Kao: Writing – review & editing, Visualization, Methodology. Thi Kim Ngan Nguyen: Validation, Supervision. Ching-I Lin: Supervision. Tzu-Wen L. Cross: Supervision. Shyh-Hsiang Lin: Writing – review & editing, Supervision, Methodology, Investigation, Funding acquisition, Conceptualization.

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