Dr. Kathie Mathis, Psy.D, D.D., CAMS-IV, CDAC, CSAC ,  CEO California Cognitive Behavioral Institute

Humans have over 100 trillion bacteria, highly abundant in the intestinal tract. Evidence suggests that intestinal microbiota is associated with the neuro-endocrine-immune pathways and can be associated with various mood disorders. This review summarizes findings from studies looking into neurobiochemical, neuroendocrine, and neuroimmune system mechanisms of the gut–brain axis to determine the relationship between intestinal microbiota and mood disorders.

Intestinal microbiota is considered to be associated with the neuro–endocrine–immune pathways, generating the concept of the gut–brain axis. The first evidence of the gut–brain axis came from a work of an army surgeon through monitoring gastric juices secreted by intragastric fistula he found that intestinal function was related with mood. About 60% of anxiety and depression patients are described to have intestinal function disturbance, such as in irritable bowel syndrome (IBS). Recently, IBS has also been related to changes in intestinal microbiota, including reduced microbiota species and genus potent instability. Meanwhile, many animal studies suggest that intestinal microbiota disturbances could induce an increased visceral pain response and changes of brain chemistry and behavior.

The research clearly shows the importance of the gut microbiota in early life through adulthood effects neurodevelopment in emotional wellbeing and our emotions, including anger.  Counselors and other mental health professionals need to provide education on the roles of diet, nutrition and development of emotional behavior from infancy into adulthood. Anger is not a loss of emotional control entirely. It has factors associated with neuro-endocrine-immune pathways and  probiotic, nerobiological mechanisms effecting mood, mental disorders, depression and anger.


Microbiota can secrete many kinds of neurotransmitters  (regulating memory, attention, learning and mood).  Some intestinal microbiota such as Lactobacillus acidophilus, Bifidobacterium infantis, Bifidobacterium, Candida, Streptococcus have proven mental illness therapeutic effects through secreting neurotransmitters (gamma-aminobutyric acid [GABA], 5-HT, glycine, catecholamine) or regulating endocannabinoid expression. Neuroactive molecules secreted by intestinal microbiota have the ability of regulating nerve signals and can affect neuropsychiatric parameters such as sleep, appetite, mood and cognition.

Some neurotransmitter changes in stress state may not be caused by stress itself, but by the intestinal microbiota. Crumeyrollearias et al. found that in GF rats homovanillic acid (HVA) concentrations decreased in the anterior cortex, hippocampus, and striatum and lead to low HVA/dopamine.  Depression is associated with a downregulation of tryptophan metabolism presented by the increased plasma ratio of kynurenine/tryptophan. Kelly et al.

Vagus nerve

The intestinal tract is controlled by intrinsic and extrinsic factors, the intrinsic factor is intestinal neural system also called the second brain which is composed of 200–600 million neurons. The intestinal neural system is also controlled by extrinsic factor including the vagal and sacral parasympathetic nerve fibers and visceral sympathetic nerve fiber. The vagus nerve is the primary connection between the brain and proximal intestinal tract, sacral parasympathetic nerve fiber connects the distal third colon. The humoral connection includes the HPA axis, which is responsible for regulating stress response and intestinal endocrine cells, secreting neuropeptides and intestinal peptide that act locally and through the vagus nerve and spinal cord afferent or blood brain barrier to act on the brain .

Bravo et al. showed that L. rhamnus regulated behavioral and physical reactions through the vagus nerve (all are anxiety behavior related receptors). The amygdala can regulate fear and anxiety behavior, thus indicating that reduced GABA receptor subtypes induced by L. rhamnus has adaptive advantage in stress state.  Interestingly indicating that the vagus nerve is an important pathway for regulating the gut–brain axis and microbiota.

Pathological ecological imbalance can increase intestinal vagus nerve activity, inducing low grade intestinal inflammatory reaction leading to anxiety-like behavior.  In other words, the vagus nerve could be seen as the pathway of behavioral change, having anxiety (through intestinal inflammatory reaction) and anti-anxiety (through probiotics) effects.


The imbalances in the intestinal tract and the changes in permeability lead to the production of a kind of proinflammatory endotoxin—lipopolysaccharide (LPS), which can enter the blood system. LPS is important for regulating the neural system, it increases the activity of the amygdala which is responsible for regulating emotion, affecting the physical activity of the brain and regulating the further production of neuropeptides. LPS when given to healthy people can produce inflammatory cytokine and increase norepinephrine in plasma, which has been linked to high depression mortality .

Some studies have shown that just a small amount of LPS could lead to symptoms of acute anxiety and depression, cognition deficit, emotional change and an increase in visceral pain sensitivity.

(Counseling Today, 2020, NCIH, 2018, Front Psychology, 2018)