Depression and gut bacteria: What is the link?

In this study, researchers at Oxford Population Health, working with colleagues in the Netherlands, investigated the relationship between the composition and diversity of the gut microbiota with symptoms of depression.

They examined data from 1,133 participants in the Rotterdam Study. As part of their analysis, they made sure to control for lifestyle factors and medication use. For example, they only included individuals who were not taking antidepressants.

This was to avoid measuring changes in the gut microbiota that are a consequence of the depression — or the medication — rather than a cause.

Various bacteria identified showed a potential involvement in the way people produce neurotransmitters, particularly those linked to depression such as glutamate.

The researchers then replicated and validated these findings using data from another observational study, called the HELIUS study.

The results of this research may one day lead to the development of novel treatments for conditions such as depression.

Dr. Najaf Amin, study author and senior research associate at Oxford Population Health, highlighted the key findings to Medical News Today, saying that the research team has “identified 13 types of bacteria [12 genera and one family] associated with depression.”

“Eggerthella, Hungatella, Sellimonas, and Lachnoclostridium are more abundantly found, while Coprococcus, Lachnospiraceae UCG001, Ruminococcusgauvreauii group, Eubacterium ventriosum, Subdoligranulum, Ruminococcaceae (UCG002, UCG003, UCG005), and [the] family Ruminococcaceae were less abundant in individuals with higher symptoms of depression,” she specified.

“These bacteria are known to be involved in the metabolism of some key molecules including glutamate and butyrate through which these bacteria can influence depression.”

– Dr. Najaf Amin

Dr. Amin said that “large and carefully conducted studies on the association of gut microbiome with depression were missing.” According to her, “[s]uch studies are the first step towards understanding the pathogenesis, providing biomarkers and therapeutic targets for the disease.”

“Since gut microbiome is primarily determined by the lifestyle factors, diet in particular, once causality is established, the therapy would be as simple as modification of diet or the use of probiotics,” she noted.

“Further, depression is both an underdiagnosed and overdiagnosed disease. A biomarker will enable an objective measurement for depression, which is currently lacking, thus improving the diagnosis,” Dr. Amin explained.

New York-based anti-aging and regenerative medicine doctor, Dr. Neil Paulvin, not involved in the study, told MNT that “we know that the microbiome affects our mood.”

“The microbiome produces neurotransmitters such as nana, serotonin, and norepinephrine. This is part of the future of mental health,” he added.

“We need to find the specific combination of gut bacteria that are good and bad for anxiety. For example, which bacteria can activate GABA [gamma-aminobutyric acid, a neurotransmitter] to help anxiety, which can affect serotonin to help with depression, and if fecal microbiota transplant will be an answer for depression and anxiety.”

– Dr. Neil Paulvin

Dr. Paulvin highlighted that “there are pill psychobiotics [probiotics that affect mood] currently in development.”

“We are now cultivating the information to develop programs in the future,” Dr. Paulvin said.

Dr. James Giordano, Pellegrino professor of Neurology and Biochemistry at Georgetown University Medical Center, also not involved in this research, commented that “this is a very well done study that controlled for several potentially interfering variables, and in so doing, demonstrated the role of certain gut microbiome species in providing chemical modulators that are known to have both direct and indirect effect on brain chemistry involved in cognitive and emotional function.”

“Namely, these gut species, Eggerthella and Eubacterium ventriosum, have been shown to produce butyrate — an important precursor molecule to GABA, a brain chemical that functions in regulatory control of glutamate,” he explained.

“Additionally, these species were shown to produce serotonin, which has direct effects upon the enteric nervous system, the gut-brain axis, and in these ways, can affect serotonin levels and activity in the brain, which in turn, are important to aspects of cognitive, emotional, and behavioral function.”

“Overactivity of glutamate transmission in the brain has been shown to contribute to several features of depressive and anxiety disorders, and thus, gut microbiome contribution to GABA-mediated and serotonin-mediated control of brain glutamate activity (primarily via modulation of the vagus nerve) may be an important mechanism for maintaining mental health.”

– Dr. James Giordano

“[T]he study [also] revealed that certain other species of gut [bacteria] can exert disruptive effects on the microenvironment of the gut, the enteric nervous system, the gut-brain axis, brain chemistry, and the expression of signs and symptoms of depressive and anxiety disorders.”

“Thus, overgrowth of these species, and undergrowth or underactivity of beneficial species can produce local and systemic inflammatory states, which can disrupt the biochemical and physiological stability of the brain, and contribute to the development and exacerbation of neuro-psychiatric conditions,” Dr. Giordano explained.

Dr. Amin noted that “it is possible to alter the composition of these [populations of] bacteria. This is possible through the use of prebiotics and probiotics. For instance, the butyrate-producing bacteria can be altered by the consumption of high-fiber diets, e.g. fresh fruits, whole grains, and vegetables.”

Dr. Giordano agreed, telling MNT that “an important take-away message afforded by this study’s findings is that gut health via [the] stability of the gut microbiome is important to maintaining brain functions that are involved in thought, mood and behavior.”

“The increasing knowledge about the gut microbiome and the gut-brain axis fortifies that the prudent use of pre- and probiotics can be of value in sustaining both gut and brain health,” he said.