Analysis of Faecal Microbiota and Small ncRNAs in Autism: Detection of miRNAs and piRNAs with Possible Implications in Host–Gut Microbiota Cross-Talk

Abstract

Intestinal microorganisms impact health by maintaining gut homeostasis and shaping the host immunity, while gut dysbiosis associates with many conditions, including autism, a complex neurodevelopmental disorder with multifactorial aetiology. In autism, gut dysbiosis correlates with symptom severity and is characterised by a reduced bacterial variability and a diminished beneficial commensal relationship. Microbiota can influence the expression of host microRNAs that, in turn, regulate the growth of intestinal bacteria by means of bidirectional host-gut microbiota cross-talk. We investigated possible interactions among intestinal microbes and between them and host transcriptional modulators in autism. To this purpose, we analysed, by “omics” technologies, faecal microbiome, mycobiome, and small, non-coding-RNAs (particularly miRNAs and piRNAs) of children with autism and neurotypical development. Patients displayed gut dysbiosis related to a reduction of healthy gut micro- and mycobiota as well as up-regulated transcriptional modulators. The targets of dysregulated non-coding-RNAs are involved in intestinal permeability, inflammation, and autism. Furthermore, microbial families, underrepresented in patients, participate in the production of human essential metabolites negatively influencing the health condition. Here, we propose a novel approach to analyse faeces as a whole, and for the first time, we detected miRNAs and piRNAs in faecal samples of patients with autism.

Gut Microbiota Profiles in Children and Adolescents with Psychiatric Disorders

“…Six studies revealed a decreased Bacteroidetes/Firmicutes ratio in ASD [ 30 , 34 , 41 , 49 , 54 , 62 ]. Contradictory findings were reported by the same number of authors [ 36 , 38 , 40 , 52 , 53 , 57 ], and in four other studies, no significant differences were observed [ 28 , 37 , 39 , 64 ]. A similar number of studies reported decreased, increased, or no specific difference in the abundance of Bacteroidetes , Firmicutes , and Actinobacteria .…”

“…Lower amounts of Prevotella or certain Prevotella species in ASD patients were found in several studies [ 25 , 30 , 31 , 37 ]. In contrast, some authors found the opposite [ 33 , 40 , 42 , 55 , 57 ].…”

“…Lower alpha diversity (microbial diversity within the same group’s samples) in ASD patients was described in ten studies [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], while in thirteen cases, higher alpha diversity was found [ 19 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Another eleven studies did not reveal any significant differences in alpha diversity between ASD patients and healthy controls [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. In the rest of the studies, information about alpha diversity differences were not provided [ 58 , 59 , 60 , 61 , 62 , 63 , 64 ].…”

Exploration of the relationship between gut microbiota and fecal microRNAs in patients with major depressive disorder

“…Using fluid samples such as blood and cerebrospinal fluid or brain-associated tissues, such as the cortex and basolateral amygdala, the associations between miRNAs and depression in humans have been reported in a review article 24 , despite lacking robust findings to serve as potential biomarkers for depression. Recently, an autism-associated study using fecal samples found that autistic patients with gut dysbiosis were also associated with transcriptional modulators, which were involved in intestinal permeability and inflammation 6 . However, as far as we know, there are no studies exploring miRNAs' roles in fecal samples for depression.…”

“…In particular, depressed individuals commonly reported gastrointestinal dysfunction and disordered bowel habit 3 , indicating the link between the gut and brain health. In this regard, recent work exploring the causal effects of gut microbiota on human health has suggested the interactions between gut microbiota and host microRNAs (miRNAs) [4][5][6] .…”