這項新研究透過一個月大的幼豬(等同人類嬰兒期，方便大腦發展及腸道菌叢得觀察)，開始先透過蒐集昇結腸內含相關的腸道菌叢分析，然而檢測血液以及大腦中一些特定檢測物質的濃度。研究發現，糞便中擬桿菌( Bacteroides)以及縮狀菌(Clostridium)濃度比較高的，血液中的肌醇(myo-inositol)濃度就比較高。而Butyricimonas這種桿菌濃度高的，n-乙醯天門冬胺酸(n-acetylaspartate ，簡稱NAA)這種神經傳導物質(與興奮有關),就會高些。但瘤胃球菌(Ruminococcus )濃度高的，NAA濃度比較低。
然而要做檢測，血液還是比較直接且容易蒐集的檢體，因此研究人員想了解血液濃度得哪些代謝物質與腸道菌的多寡有關，結果發現，可體松以及血清素與腸道菌的關連比較明顯。數據顯示擬桿菌( Bacteroides)濃度高者，血清素濃度會比較高。瘤胃球菌(Ruminococcus )濃度高的，血清素和可體松的濃度都會比較低。許多自閉症患者，其血清素和可體松的濃度都呈現異常。
- Austin T. Mudd, Kirsten Berding, Mei Wang, Sharon M. Donovan, Ryan N. Dilger. Serum cortisol mediates the relationship between fecal Ruminococcus and brain N-acetylaspartate in the young pig. Gut Microbes, 2017; 1 DOI: 10.1080/19490976.2017.1353849
The researchers found predictive relationships between the fecal microbiota and serotonin and cortisol, two compounds in the blood known to be influenced by gut microbiota. Specifically, Bacteroideswas associated with higher serotonin levels, while Ruminococcuspredicted lower concentrations of both serotonin and cortisol. Clostridium and Butyricimonas were not associated strongly with either compound.
Again, Mudd says, the results supported previous findings related to ASD. "Alterations in serum serotonin and cortisol, as well as fecal Bacteroides and Ruminococcus levels, have been described in ASD individuals."
Based on their initial analyses, the researchers wanted to know if there was a three-way relationship between Ruminococcus, cortisol, and NAA. To investigate this further, they used a statistical approach known as "mediation analysis," and found that serum cortisol mediated the relationship between fecal Ruminococcus abundance and brain NAA concentration. In other words, it appears that Ruminococcus communicates with and makes changes to the brain indirectly through cortisol. "This mediation finding is interesting, in that it gives us insight into one way that the gut microbiota may be communicating with the brain. It can be used as a framework for developing future intervention studies which further support this proposed mechanism," Dilger adds.
"Initially, we set out to characterize relationships between the gut microbiota, blood biomarkers, and brain metabolites. But once we looked at the relationships identified in our study, they kept leading us to independently reported findings in the autism literature. We remain cautious and do not want to overstate our findings without support from clinical intervention trials, but we hypothesize that this could be a contributing factor to autism's heterogenous symptoms," Mudd says. Interestingly, in the time since the researchers wrote the paper, other publications have also reported relationships between Ruminococcus and measures of brain development, supporting that this might be a promising area for future research.
Dilger adds, "We admit this approach is limited by only using predictive models. Therefore, the next step is to generate empirical evidence in a clinical setting. So it's important to state that we've only generated a hypothesis here, but it's exciting to consider the progress that may be made in the future based on our evidence in the pre-clinical pig model."