Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. We extracted data from case–control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.

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寻找自闭症胃肠道炎症：非侵入性胃肠道标志物的系统回顾和荟萃分析

自闭症人群中胃肠道症状和炎症性胃肠道疾病的发生率较高。然而，目前尚不清楚自闭症是否与胃肠道炎症升高有关，因为检查非侵入性粪便生物标志物的研究报告了相互矛盾的结果。为了了解研究现状并找出差距，我们对测量自闭症和非自闭症样本中胃肠道炎症非侵入性标志物的研究进行了系统回顾和荟萃分析。我们的检查重点是粪便生物标志物，因为采样是非侵入性的，这些标志物是胃肠道炎症过程的直接反映。我们从检查胃肠道炎症粪便标志物的病例对照研究中提取了数据。我们检索了 PubMed、Embase、Cochrane CENTRAL、CINAHL、PsycINFO、Web of Science Core Collection 和 Epistemonikos，以及截至 2023 年 4 月 14 日发表的纳入研究的向前和向后引用 (PROSPERO CRD42022369279)。很少有研究检查自闭症人群胃肠道炎症的粪便标记物，并且许多已建立的标记物尚未进行研究。对钙卫蛋白 (n = 9) 和乳铁蛋白 (n = 3) 的研究进行荟萃分析。钙卫蛋白研究的荟萃分析共纳入了 508 名自闭症儿童和青少年以及 397 名非自闭症儿童和青少年，未发现显着的组间差异（ROM：1.30 [0.91，1.86]）。在兄弟姐妹的研究和不排除有胃肠道症状的非自闭症对照的研究中，钙卫蛋白的估计差异较低。乳铁蛋白研究的荟萃分析共纳入了 139 名自闭症参与者和 75 名非自闭症对照者，结果发现没有显着的组间差异（ROM：1.27 [0.79，2.04]）。本系统评价和荟萃分析中包含的所有研究均针对儿童和青少年进行了检查。许多研究都纳入了患有胃肠道症状的非自闭症对照，这限制了研究结果的有效性。大多数胃肠道炎症研究都集中在 12 岁以下儿童，很少有研究包括青少年参与者。大多数涉及四岁或以下参与者的研究并未考虑年龄对钙卫蛋白水平的影响。未来的研究应该筛选相关的混杂因素，纳入更大的样本，并探索自闭症青少年和成人的胃肠道炎症。没有证据表明，通过钙卫蛋白和乳铁蛋白测量，自闭症儿童和青少年的胃肠道炎症水平较高。然而，初步证据表明，一部分自闭症参与者可能存在较高的钙卫蛋白水平，他们的临床特征可能是更严重的胃肠道症状和更高水平的自闭症特征。