The prevalence of psychiatric disorders such as major depression disorder (MDD) is increasing
rapidly. Despite advancements in the development of therapeutics, current treatment options
have not reached optimal efficacy.
Recent interest has been drawn towards the importance of the biochemical signalling between
the gastrointestinal tract and the central nervous system also known as the
"microbiome-gut-brain axis". The pathogenesis of gut microbiota in extra intestinal diseases
was inspired by massive studies in germ free (GF) animals, which indicated that the gut
microbiota plays a role in the normal regulation of behaviour that are relevant to mood,
anxiety and stress. However, the exact mechanisms by which intestinal dysbiosis are involved
in the development of psychiatric diseases are not completely clarified.
A new method to alter the composition of the gastrointestinal microbiota involves fecal
microbiota transplantation (FMT). The goal of FMT is to introduce or restore a stable
microbial community in the gut by transplanting intestinal microbiota from a healthy donor to
the patient. FMT, as a microbiota-target therapy, is arguably very effective for curing
recurrent Clostridium difficile infection and has good outcomes in other intestinal diseases.
At the same time, applications in previously unexpected areas, including metabolic diseases,
neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors have shown
health enhancing results. FMT has initially been conducted using colonoscopy. However, recent
evidence has shown that treatment with frozen FMT capsules (to be taken orally) is also safe
and beneficial in restoring the gut microbiota in patients with various diseases As FMT
capsules may be an effective, pragmatical adjuvant therapy (in addition to standard
treatment) for depression, this project is aimed at (1) investigating for the first time if
single administration of FMT capsules ameliorates depressive symptoms in patients with
moderate to severe MDD 4 weeks after treatment and (2) establishing the safety profile of
encapsulated FMT in MDD. Furthermore, we will also test if (3) FMT capsules modulates immune
signalling and inflammatory processes, (4) Hypothalamic-pituitary-adrenal (HPA) axis
responses, (5) neurogenesis, (6) energy balance hormones, (7) gut microbiota composition and
(8) brain perfusion, structure and activation.