Early changes of fecal short‐chain fatty acid levels in patients with mild cognitive impairments

Abstract

AbstractBackgroundMild cognitive impairment (MCI) is with great risk for the conversion to Alzheimer’s disease (AD). The aim of present study wanted to explore whether fecal Short‐chain fatty acids (SCFAs) could be used as the biomarker for the identification of MCI patients and to examine the relationship between fecal SCFAs and amyloid‐β deposition in the brain.MethodsA cohort of 32 MCI patients and 27 NC were recruited in our study. Fecal levels of SCFAs were measured using chromatography and mass spectrometry. Disease duration, ApoE genotype, body mass index, constipation, and diabetes were evaluated. To assess cognitive impairment, we used the Mini‐Mental Status Examination (MMSE). To assess brain atrophy, the degree of medial temporal atrophy (MTA score, Grade 0‐4) was measured by structural MRI. β‐amyloid positron emission tomography (PET) with 18F‐AV‐45 was performed in seven MCI patients to detect and quantify Aβ deposition in the brain.ResultsCompared with NC, MCI patients had significantly lower fecal levels of acetic acid, butyric acid, and caproic acid. Among fecal SCFAs, acetic acid performed the best in discriminating MCI from NC, achieved an AUC of 0.752 (p = 0.001, 95% CI: 0.628‐0.876), specificity of 66.7% and sensitivity of 75%. By combining fecal levels of acetic acid, butyric acid and caproic acid, the diagnostic specificity was significantly improved, reaching 88.9%. To better verify the diagnostic performance of SCFAs, we randomly assigned 80% of participants into training dataset and 20% into testing dataset. Only acetic acid showed significantly difference between these two groups in the training dataset. Based on the fecal levels of acetic acid, we achieved the ROC curve. Next, the ROC curve was evaluated in the independent test data and 66.7% (4 in 6) of MCI patients, and 80% (4 in 5) of NC could be identified correctly. Subgroup analysis showed that reduced fecal SCFAs in MCI group were negatively associated with Aβ deposition in cognition‐related brain regions.ConclusionOur findings suggest that gut metabolite SCFAs have the potential to serve as early diagnostic biomarkers for distinguishing patients with MCI from NC and could serve as potential targets for preventing AD.