Serotonin can reduce the ability of some intestinal pathogens to cause deadly infections


Serotonin, a chemical known for its role in producing feelings of well-being and happiness in the brain, can reduce the ability of some intestinal pathogens to cause deadly infections, new research by UT Southwestern scientists suggests.

The findings, publishing online today in Cell Host & Microbe, could offer a new way to fight infections for which few truly effective treatments currently exist.

Although the vast majority of research on serotonin has centered on its effects in the brain, about 90 percent of this neurotransmitter – a chemical that nerve cells use to communicate with each other – is produced in the gastrointestinal tract, explains study leader Vanessa Sperandio, Ph.D., a professor of microbiology and biochemistry at UT Southwestern Medical Center.

In humans, trillions of bacteria live within this space. Most of these gut bacteria are beneficial, but pathogenic bacteria can also colonize the gastrointestinal tract, causing serious and potentially fatal infections.

Because gut bacteria are significantly affected by their environment, Sperandio, along with UTSW doctoral student Aman Kumar, laboratory manager Regan Russell, and their colleagues, wondered whether the serotonin produced in the gut can affect the virulence of pathogenic bacteria that infect the gastrointestinal tract.

The researchers worked with Escherichia coli O157, a species of bacteria that causes periodic outbreaks of often deadly foodborne infection. The team grew these pathogenic bacteria in petri dishes in the lab, then exposed them to serotonin.

Gene expression tests showed that serotonin significantly reduced the expression of a group of genes that these bacteria use to cause infections.

Additional experiments using human cells showed that the bacteria could no longer cause infection-associated lesions on the cells if these bacteria were exposed to serotonin.

Next, the researchers examined how serotonin affected virulence in living hosts. Using mice, the researchers studied how serotonin might change the ability for Citrobacter rodentium – a mouse gut bacterium often used as an analog for E. coli in humans—to infect and sicken their hosts.

These mice were genetically modified to either over- or underproduce serotonin in their gastrointestinal tracts. Those that overproduced this neurotransmitter were less likely to become colonized by C. rodentium after being exposed to this bacterium or had relatively minor courses of illness.

Treating mice with fluoxetine (sold under the brand name Prozac) to increase serotonin levels prevented them from getting sick from C. rodentium exposure. However, the mice that underproduced serotonin became much sicker after bacterial exposure, often dying from their illness.

Further experiments identified the receptor for serotonin on the surfaces of both E. coli and C. rodentium, a protein known as CpxA. Because many species of gut bacteria also have CpxA, it’s possible that serotonin could have wide-ranging effects on gut bacterial health, Sperandio says.

In the future, she adds, she and her colleagues plan to study the feasibility of manipulating serotonin levels as a way of fighting bacterial infections in the gastrointestinal tract. Currently, few available antibiotics can effectively fight E. coli O157 – some antibiotics actually worsen the consequences of infection, causing the bacteria to release more damaging toxins.

“Treating bacterial infections, especially in the gut, can be very difficult,” Sperandio says. “If we could repurpose Prozac or other drugs in the same class, it could give us a new weapon to fight these challenging infections.”

Depression is a predominant, fetal and extremely recurring mental illness described by anhedonia, depressed mood, plus great suicide rates.1 As per the World Health Organization (WHO), depressive illnesses are the utmost heavy sicknesses in the general public, besides they may perhaps become the principal foundation of disability globally.2

In latest periods, numerous concepts have made an effort to clarify the pathogenesis of major depressive disorder (MDD), containing neurotransmission insufficiency,3 neurotrophic changes,4 endocrine‐immune system dysfunction,5 and neuroanatomical irregularities.6 However, there have not been any globally approved theories.

Therefore, there is a need to determine the etiology of depression and neurobiological mechanisms for the avoidance and treatment of this illness.

Multiple data support that gut microbiota has an effect on gastrointestinal physiology and central nervous system (CNS) function plus behavior via the microbiota‐gut‐brain axis.7, 8, 9 Serotonin (5‐hydoxytryptamine, 5‐HT) is a kind of neurotransmitter both in the central nervous system and in the peripheral nervous system (CNS/PNS), which has been implicated in the etiology of numerous disease states, including depression, anxiety, social phobia, schizophrenia, obsessive‐compulsive, and panic disorders.

Latest research recommended that some prebiotic and probiotic treatment could result in reversal of behavioral deficits, adjust the composition of gut microbiota, rise in peripheral levels of the serotonin precursor tryptophan, and alter 5‐hydroxyindoleacetic acid (5‐HIAA) and dihydroxyphenylacetic acid (DOPAC) levels in the brain of animal models of depression and chronic stress.10

Precisely, the lack of GI microbes in rats leads to decreased expression of brain‐derived neurotrophic factor in the cortex and hippocampus, in addition to an inflated hypothalamic‐pituitary‐adrenal (HPA) axis reaction to stress.11

Given the capability of the gut microbiota to influence serotonin and its precursor, tryptophan,12 control the stress response 13 plus control cognition 14 in addition to behavior,15 the potential prominence of the gut microbiota to psychiatry in general and to depression definitely is obvious.

In‐depth research is desired to cross‐examine this fascinating proposal. Numerous lines of proof, comprising the current reports from Hsiao and colleagues,16 prove that, in the gut, microbial‐derived metabolites have the impact on the creation of serotonin which in turn influences host physiological functions.17

As not all probiotics are beneficial in depression, we selected L. rhamnosus and Bifidobacterium longum. It has been reported that they can advance expressive behavior in animals.18, 19 In this study, we selected prebiotics (fructo‐oligosaccharide and galactooligosaccharide, FOS/GOS) and probiotics (Bifidobacterium longum and L. rhamnosus) and intended to identify the difference in probable antidepressant properties of them in the chronic unpredictable mild stress (CUMS) rat model of depression on the adult behavioral phenotype. Especially, the serotonin and crucial systems participating in depression along with brain‐gut communication were the focus of this study.

The results implied that probiotics and prebiotics exert antidepressive effects in mouse model of CUMS‐induced depression. We established in our experiment that regulating gut microbiota through probiotics and prebiotics has a considerable impact on the modulation of tryptophan metabolism, especially L. rhamnosus. 16S rRNA gene sequencing showed that CUMS‐induced depression suggestively changed not only the composition of gut microbiota but also the abundance of phylum Firmicutes and other levels.

Furthermore, correlation analysis exposed that phylum Firmicutes were strongly correlation with changed colonic and Frontal CX 5‐HT metabolites. Overall, these outcomes specify that CUMS‐induced depression disturbs the gut microbiota at the profusion level and modifies the host 5‐HT metabolism.

Probiotics and prebiotics have an effect of regulating the intestinal flora composition and 5‐HT metabolism, especially L. rhamnosus. Generally, the controlled gut microbiota‐associated 5‐HT metabolites might be possible biomarkers to review the functional impacts of depression.

Regulating the gut microbiota configuration by adding L. rhamnosus might be a treatment for depression. However, further studies are required to substantiate the clinical use of probiotics.


1. Faulconbridge LF, Wadden TA, Berkowitz RI, et al. Fabricatore, Changes in symptoms of depression with weight loss: results of a randomized trial. Obesity. 2009;17:1009‐1016. [PMC free article] [PubMed] [Google Scholar]

2. Moussavi S, Chatterji S, Verdes E, Tandon A, Patel V, Ustun B. Responding to public and private politics: Corporate disclosure of climate change strategies. Strateg Manag J. 2009;30(11):1157‐1158. 10.1002/smj.796. [CrossRef] [Google Scholar]

3. Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16:383‐406. [PMC free article] [PubMed] [Google Scholar]

4. Guilloux J‐P, Douillard‐Guilloux G, Kota R, et al. Corporate social responsibility: A three‐domain approach. Bus Ethics Q. 2003;13(4):503‐530. [Google Scholar]

5. Müller N, Schwarz M. Machiavellianism, stakeholder orientation, and support for sustainability reporting. Bus Ethics Eur Rev. 2018;27(3):271‐285. [Google Scholar]

6. Schlösser RG, Wagner G, Koch K, Dahnke R, Reichenbach JR, Sauer H. The perceived importance of ethics and social responsibility on organizational effectiveness: A survey of marketers. J Acad Mark Sci. 1995;23(1):49‐56. [Google Scholar]

7. Evrensel A, Ceylan ME. Shareholders as norm entrepreneurs for corporate social responsibility. J Bus Ethics. 2009;94(2):177‐191. [Google Scholar]

8. Foster JA, McVey Neufeld KA. Exogenously driven CSR: Insights from the consultants’ perspective. Bus Ethics Eur Rev. 2014;23(3):258‐271. [Google Scholar]

9. Luna RA, Foster JA. Research into quality management and social responsibility. J Bus Ethics. 2011;102(4):623‐638. [Google Scholar]

10. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacterium infantis: an assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008;43:164‐174. [PubMed] [Google Scholar]

11. Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic‐pituitary‐adrenal system for stress response in mice. J Bus Ethics. 2004;558:263‐275. [PMC free article] [PubMed] [Google Scholar]

12. Dash S, Clarke G, Berk M, Jacka FN. An external perspective on CSR: What matters and what does not? Bus Ethics Eur Rev. 2017;26(4):396‐397. [Google Scholar]

13. Moloney RD, Desbonnet L, Clarke G, et al. The microbiome:stress, health and disease. Mamm Genome. 2014;25:49‐74. [PubMed] [Google Scholar]

14. Desbonnet L, Clarke G, Shanahan F, et al. Microbiota is essential for social development in the mouse. Mol Psychiatry. 2014;19:146‐148. [PMC free article] [PubMed] [Google Scholar]

15. Ohland CL, Kish L, Bell H et al. Effects of Lactobacillus helveticus on murine behavior are dependent on diet and genotype and correlate with alterations in the gut microbiome. Psychoneuroendocrinology 2013; 38:1738‐1747. [PubMed] [Google Scholar]

16. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264‐276. [PMC free article] [PubMed] [Google Scholar]

17. Ridaura V, Belkaid Y. Gut microbiota: the link to your second brain. Cell. 2015;161:193‐194. [PubMed] [Google Scholar]

More information: Aman Kumar et al. The Serotonin Neurotransmitter Modulates Virulence of Enteric Pathogens, Cell Host & Microbe (2020). DOI: 10.1016/j.chom.2020.05.004


Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.