Microbiota fasting-related changes ameliorate cognitive decline in obesity and boost ex vivo microglial function through the gut-brain axis.

The role of microglial cells in this process remains underexplored.

在这个过程中，小胶质细胞的作用尚未得到充分探索。

To investigate how diet-induced changes in gut microbiota influence cognitive function in individuals with obesity and their microglial activity, and to determine the impact of specific dietary interventions.

为了研究饮食引起的肠道微生物群变化如何影响肥胖个体的认知功能及其小胶质细胞活性，并确定特定饮食干预的影响。

Methods

This study included 96 participants with obesity who were randomised into three dietary intervention groups: Mediterranean diet (Med), alternate-day fasting (ADF) and ketogenic diet (Keto).

该研究包括96名肥胖参与者，他们被随机分为三组进行饮食干预：地中海饮食（Med）、隔日禁食（ADF）和生酮饮食（Keto）。

Cognitive performance and microbiota composition were assessed pre-intervention and post-intervention.

在干预前后评估了认知表现和微生物群组成。

The effects of microbiota-related changes on microglial function were further evaluated in mice models through faecal transplantation and in vitro model with microbiota exosome treatment.

通过粪便移植和微生物群外泌体处理的体外模型，进一步评估了微生物群相关变化对小鼠模型中微胶质细胞功能的影响。

Results

Both the Keto and ADF groups demonstrated significant weight loss, but cognitive performance improved most notably in the ADF group, in association with reduced inflammation.

无论是生酮饮食组还是间歇性禁食组都显示出显著的体重减轻，但与炎症减少相关联，间歇性禁食组的认知表现改善最为显著。

Diet-related microbiota composition was correlated with the cognitive outcomes in the human study.

饮食相关的微生物群组成与人类研究中的认知结果相关。

Mice models confirmed that the cognitive benefits of ADF were microbiota-dependent and linked to enhanced microglial phagocytic capacity and reduced inflammation, accompanied by changes in microglia morphology.

小鼠模型证实，抗衰因子(ADF)的认知益处依赖于微生物群，并与微胶质细胞吞噬能力的增强和炎症的减少有关，同时伴随着微胶质细胞形态的变化。

Conclusions

Fasting-induced modifications in gut microbiota contribute to cognitive improvement in individuals with obesity, with microglial cells playing a crucial mediatory role.

禁食引起的肠道微生物群改变有助于肥胖个体的认知改善，微胶质细胞在其中扮演了关键的介导作用。

Among the interventions, ADF most effectively enhanced microglial function and cognitive performance, suggesting its potential as a therapeutic strategy for obesity-related cognitive decline.

在这些干预措施中，间歇性禁食（ADF）最有效地增强了小胶质细胞的功能和认知表现，这表明它作为一种治疗肥胖相关认知衰退的潜在策略的潜力。

Further studies are required to fully elucidate the underlying mechanisms.

需要进一步的研究来完全阐明潜在的机制。

trial_registration_number

NCT04453150.

NCT04453150。