Short-chain fatty acids (SCFAs) are bioactive lipids that are released into the colon as a metabolite of bacterial fermentation of dietary fibers. Beyond their function in the gastrointestinal tract, SCFAs can also have effects inthe brain, as a part of the gut-brain axis. Recent investigations into potential therapeutic interventions via the manipulation of the gut microbiome—and thus their SCFA metabolites—has been emerging as a new branch of personalized medicine,especially for mental health conditions. The current study sought to measure and localize SCFA receptors in the mouse brain. Two cell types have been implicated in the gut-brain axis: microglia and serotonergic neurons. We used fluorescenthybridization in brain sections from mice fed diets with different compositions of fat and fiber to quantify the mRNA levels of known gene markers of these two cell types and colocalize each with mRNA for free fatty acid receptors that bind SCFAs. We focused onmicroglia in the hippocampus and the serotonergic neurons of the dorsal raphe. We found high colocalization of SCFA receptors in both microglia and serotonergic neurons and discovered that SCFA receptor expression in the dorsal raphe is driven by fiber solubility, while SCFA receptor expression in the hippocampus is driven by fiber amount. Higher dietary fiber was associated with decreased tyrosine hydroxylase expression. Thus, our results indicate that the amount and solubility of dietary fiber can change gene expression in the brain’s microglia and serotonin neurons, potentially via sensitivity to circulating levels of SCFAs produced in the gut.

中文翻译：

---

膳食纤维对小鼠脑小胶质细胞和血清素能神经元短链脂肪酸受体 mRNA 的影响

短链脂肪酸 (SCFA) 是一种生物活性脂质，作为膳食纤维细菌发酵的代谢产物释放到结肠中。除了在胃肠道中发挥作用外，短链脂肪酸还可以对大脑产生影响，作为肠脑轴的一部分。最近对通过操纵肠道微生物组及其 SCFA 代谢物进行潜在治疗干预的研究已成为个性化医疗的一个新分支，特别是针对心理健康状况。当前的研究试图测量和定位小鼠大脑中的 SCFA 受体。有两种细胞类型与肠脑轴有关：小胶质细胞和血清素能神经元。我们在喂食不同脂肪和纤维成分的小鼠的脑切片中使用荧光杂交来量化这两种细胞类型的已知基因标记物的 mRNA 水平，并将每种细胞与结合 SCFA 的游离脂肪酸受体的 mRNA 共定位。我们重点关注海马体中的小胶质细胞和中缝背侧的血清素能神经元。我们发现小胶质细胞和血清素能神经元中 SCFA 受体的高度共定位，并发现中缝背侧的 SCFA 受体表达由纤维溶解度驱动，而海马中的 SCFA 受体表达由纤维量驱动。较高的膳食纤维与酪氨酸羟化酶表达降低有关。因此，我们的结果表明，膳食纤维的含量和溶解度可以改变大脑小胶质细胞和血清素神经元的基因表达，这可能是通过对肠道中产生的 SCFA 循环水平的敏感性来实现的。