**Author details**

Clinical trials targeting not only the cross-talk between the gut microbiota and the central nervous system focus on its association with various neuropsychiatric and neurodegenerative disorders (anxiety, depression, dementia, etc.), but also on its involvement in the regulation of hunger/satiety and in pathologies affecting the digestive tract (**Table 1**). The therapeutic solutions investigated these clinical trials involve the use of prebiotics and probiotics, dietary

**No. Clinical trial Main objective Status Reference**

To assess the efficiency of fecal microbiota transplant in treating irritable bowel syndrome

To investigate the effect of a Mediterranean diet low in processed meat on the gut microbiota and age-related declines (changes in adiposity, cognitive function and cardiometabolic risk)

To examine whether the gut microbiota is involved in the modulation of sleep disorders in patients with brain traumatic

injury

**Table 1.** Clinical trials related to investigation of gut-brain axis in relationship with mental health.

Recruiting https://clinicaltrialbase.

Recruiting https://clinicaltrialbase.

Recruiting https://clinicaltrialbase.

com/study/NCT03125564/

com/study/NCT03020186/

com/study/NCT02849028/

Reports of already completed trials support the findings of preclinical trials, demonstrating that modulation of gut microbiota results in anxiolytic effect without a direct intervention on neurotransmitter circuitries. For example, the reported results of Schmidt et al. [93], after completion of trial, supported previous evidence that fructooligosaccharides, or Bimuno® galactooligosaccharides supplementation lowered neuroendocrine stress response, measured by cortisol awakening response. Rao et al. [94] reported that supplementation with specific lactic acid probiotic bacteria for 8 weeks improved the anxiety scores of patients with chronic fatigue syndrome. A complex report by Messaoudi et al. [95], involving both laboratory rats as well as healthy human volunteers showed that supplementation with a combination of *Lactobacillus helveticus* and *Bifidobacterium longum* displayed beneficial psychological effect. Finally, a recent publication regarding the effect of "4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood", [96]. These results open a promising avenue not only for age-related mental disorders, but also for selected

Gut-brain axis is a bidirectional chemical network sending information between the intestine and the brain via soluble, chemical messages as well as nervous sympathetic and parasympathetic

changes and fecal microbiota transplant.

12 FMT for patients with IBS with fecal and mucosal microbiota

13 Effects of green-MED diet via the

assessment

256 Gerontology

gut-fat-brain axis

14 The clinical research on the relationship between circadian rhythm and gut microbiota in TBI

patients

cases of psychiatric pathologies.

**7. Conclusions**

Ana-Maria Enciu1,2\*, Elena Codrici1 , Simona Mihai1 , Emilia Manole1 , Sevinci Pop1 , Eleonora Codorean1 , Cristina Mariana Niculite1,2, Laura Necula3 , Isabela Tarcomnicu4 , Elvira Gille5 and Cristiana Pistol Tanase1,6

