Objective To investigate the difference in fecal intestinal flora instructure and short chain fatty acids between children with autism spectrum disorder (ASD) and healthy children, so as to provide new clues for the prevention and treatment of ASD from the perspective of intestinal flora. Methods A total of 25 ASD childrendiagnosed in the Department of Pediatrics, Afficiated Hospital of Jiangsu University were enrolled in the ASD group from January to November 2019. Meanwhile 24 healthy children with typical growth and development who took physical examination were selected as control group. Their feces samples were collected. 16SrRNA sequencing was used to analyze the structure of the intestinal microflora, and gas chromatography was used to detect the content of short-chain fatty acids in feces. Results Compared with the control group, ASD children had a significant decrease in the abundance (Chao index and Ace index) and diversity (Shannon index) of intestinal flora (t=2.917, 2.890, 3.353, P<0.05), an increase in the abundance of Firmicutes and Proteus and a decrease in the abundance of Bacterioidetes at the phylum level(t=3.180, 5.761, 5.970, P<0.05). At the genus level, ASD children had a significant decrease in the abundance of Bacterioides, Bifidobacterium, Blautia and Streptococcus, a significant increase in the abundance of Clostridium and Sutterella (Z=2.440, 3.100, 3.620, 3.500, 4.200, 4.054, P<0.05). Compared with the control group, the levels of acetic acid, propionic acid and total short chain fatty acids in ASD group were significantly increased, while the butyric acid was significantly decreased(t=3.040, 3.220, 2.560, 4.100, P<0.05). Spearman correlation analysis showed Bifidobacterium was negatively correlated with propionic acid and total short chain fatty acids(r=-0.422,-0.412, P<0.05). Conclusions There are significant changes in the structure of intestinal flora and the content of short chain fatty acids in feces of ASD children. The increase of the content of propionic acid and the total short chain fatty acids caused by the decrease of Bifidobacterium may be related to ASD.
Key words
autism spectrum disorder /
intestinal flora /
short chain fatty acids /
gas chromatography
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Kim YS, Leventhal BL. Genetic epidemiology and insights into interactive genetic and environmental effects in autism spectrum disorders[J]. Biol Psychiat, 2015,77(1):66-74.
[2] Lyall K, Croen L, Daniels J, et al. The changing epidemiology of autism spectrum disorders[J]. Annu Rev Public Health, 2017,38:81-102.
[3] Sharon G, Cruz NJ, Kang DW, et al. Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice[J]. Cell, 2019,177(6):1600-1618.
[4] Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J]. Cell, 2013,155(7):1451-1463.
[5] Wang Y, Kasper LH. The role of microbiome in central nervous system disorders[J]. Brain Behav Immun, 2014,38:1-12.
[6] 王宏波, 王宇鹏, 谭超超, 等. 肠道微生物与自闭症谱系障碍[J]. 中国微生态学杂志, 2020,32(1):104-107.
[7] 乐涛, 卢红艳, 薛正阳, 等. 基于高通量测序分析早产认知障碍大鼠肠道菌群结构特征[J]. 中国当代儿科杂志, 2019,21(7):701-707.
[8] Mosca A, Leclerc M, Hugot JP. Gut microbiota diversity and human diseases:Should we reintroduce key predators in our ecosystem?[J]. Front Microbiol, 2016,7:455.
[9] 蒋海寅. 人类肠道微生物群落菌群多样性变化与抑郁症的相关性研究[D]. 杭州:浙江大学, 2015.
[10] 李慧慧. 肠道菌群及短链脂肪酸与精神分裂症的相关性研究[D]. 郑州:郑州大学, 2020.
[11] Kelly CR, Khoruts A, Staley C, et al. Effect of fecal microbiota transplantation on recurrence in multiply recurrent clostridium difficile infection: A randomized trial[J]. Anna Intern Med, 2016,165(9):609-616.
[12] Tomova A, Husarova V, Lakatosova S, et al. Gastrointestinal microbiota in children with autism in Slovakia[J]. Physiol Behav, 2015,138:179-187.
[13] de Theije CG, Wopereis H, Ramadan M, et al. Altered gut microbiota and activity in a murine model of autism spectrum disorders[J]. Brain Behav Immun, 2014,37:197-206.
[14] Shin NR, Whon TW, Bae JW. Proteobacteria:Microbial signature of dysbiosis in gut microbiota[J]. Trends Biotechnol, 2015,33(9):496-503.
[15] Patterson E, Cryan JF, Fitzgerald GF, et al. Gut microbiota, the pharmabiotics they produce and host health[J]. Proc Nutr Soc, 2014,73(4):477-489.
[16] Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis[J]. Cell, 2015,161(2):264-276.
[17] Coretti L, Cristiano C, Florio E, et al. Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder[J]. Sci Rep, 2017,7:45-56.
[18] Finegold SM, Summanen PH, Downes J, et al. Detection of Clostridium perfringens toxin genes in the gut microbiota of autistic children[J]. Anaerobe, 2017,45:133-137.
[19] Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice[J]. Sci Transl Med, 2014,6(263):158r-263r.
[20] Wang L, Christophersen CT, Sorich MJ, et al. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder[J]. Dig Dis Sci, 2012,57(8):2096-2102.
[21] de la Cuesta-Zuluaga J, Mueller NT, Alvarez-Quintero R, et al. Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors[J]. Nutrients, 2018,11(1):51.
[22] Kratsman N, Getselter D, Elliott E. Sodium butyrate attenuates social behavior deficits and modifies the transcription of inhibitory/excitatory genes in the frontal cortex of an autism model[J]. Neuropharmacology, 2016,102:136-145.
[23] Liu S, Li E, Sun Z, et al. Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder[J]. Sci Rep, 2019,9(1):287.
[24] MacFabe DF, Cain DP, Rodriguez-Capote K, et al. Neurobiological effects of intraventricular propionic acid in rats:Possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders[J]. Behav Brain Res, 2007,176(1):149-169.
[25] Gilbert KM, DeLoose A, Valentine JL, et al. Structure-activity relationship between carboxylic acids and T cell cycle blockade[J]. Life Sci, 2006,78(19):2159-2165.
[26] Shaaban SY, El GY, Mehanna NS, et al. The role of probiotics in children with autism spectrum disorder: A prospective,open-label study[J]. Nutr Neurosci, 2018,21(9):676-681.