Stress, Inflammation, and Microbes: A Moody Trinity, Part 2
Psychological stress leads to physical stress, anxiety, and depression. What can we do about it?
Last week, we talked about the weird role of stress and inflammation on the gut and on the mind. This is the gut-brain axis, and it can make you happy or miserable. Fortunately, for many people, the choice is up to them.
Amazingly, microbes can affect the size of your hippocampus or amygdala, brain centers that are involved with mood, appetite, and fear. The hippocampus tries to keep the HPA axis from going off the rails, and if its growth is stunted, that affects the stress reaction. A balanced immune system is achieved by dialing everything down to a low simmer. A slightly elevated immune reactivity is sufficient for the brain to sample the microbiota and other stressors, but not enough to boil over into a major inflammation.
Conducting the Orchestra
If immune cells and microbes are the key players in this biological orchestra, the HPA axis is the conductor. Short for hypothalamus-pituitary-adrenal, the HPA axis coordinates the release of hormones that build in a crescendo to the release of cortisol, the drug responsible for the fight-or-flight response.
Cortisol is the body's way of amping up the stress response by increasing blood pressure, heart rate, and breathing in order to jump from a snake or run from a badger. In the process, it also dials down the immune response: First, you escape the badger, and only then do you deal with your flu or your food poisoning. That's a reasonable response for a badger encounter, which is only a few moments of panic. But repeated over time, that lowered defense can lead to a leaky gut, converting psychological stress into microbial stress.
The HPA axis communicates with your microbiota and your brain, using several different chemicals:
Bacterial secretions: Metabolites like short-chain fatty acids.
Immune chemicals: Cytokines like interferons, interleukins, and tumor necrosis factors.
Glandular secretions: Hormones like adrenaline and cortisol.
Nerve transmission chemicals: Neurotransmitters like serotonin, dopamine, and GABA.
Your brain communicates directly with your gut through the vagus nerve, and microbes can talk back on the same channel. The baroque complexity of this network provides several different opportunities to tweak the immune reaction. Consult the figure below to see how the main components interact.
The microbiota is a central player in this concerto, and it can be changed by diet. That means you can intervene in the stress-depression axis. With the right diet and possibly some supplements, you can improve the composition of your microbiota and thus increase your resilience to stress.
Eat fiber. Fiber has been stripped from processed foods in order to make them delicious, but many of your more helpful microbes depend on fiber. The real problem with junk food is that it starves your beneficial microbes. Fiber can be found in onions, artichokes, asparagus, and many leafy greens. The Mediterranean diet emphasizes these foods and is a great model to follow.
Avoid antibiotics. These are life-saving drugs, but they have the nasty side effect of killing your gut microbes. Use prudently.
Try prebiotics. If you can't get enough fiber in your diet, prebiotics offer a similar effect. These are complex sugars that your body can't digest, but your gut microbes can.
Exercise. Oddly, sitting on your butt is not good for your gut. If exercise were a drug, it would be worth millions. It's not clear exactly how it works, but moving your body improves the quality of your microbiota.
Sync your schedule with daylight. Your microbes have circadian rhythms, just like you. If those two rhythms are coordinated, life is syncopated goodness. Get up with the sun, and your microbes will thank you.
Depression can come from grief, loss, or just a lousy boss. But it can also be caused or exacerbated by your microbiota. That is hard to wrap our heads around, but it means that we all have a chance to gain the upper hand. Be nice to your gut bugs, and you will find your mood improving. Your mileage may vary, but wouldn't it be silly not to give it a try?
References
Brachman, Rebecca A., Michael L. Lehmann, Dragan Maric, and Miles Herkenham. “Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice.” The Journal of Neuroscience 35, no. 4 (January 28, 2015): 1530–38.
Pereira, Joana da Cruz, Kieran Rea, Yvonne M. Nolan, Olivia F. O’Leary, Timothy G. Dinan, and John F. Cryan. “Depression’s Unholy Trinity: Dysregulated Stress, Immunity, and the Microbiome.” Annual Review of Psychology 71, no. 1 (2020)
Del Grande da Silva, Giovanna, Carolina David Wiener, Luana Porto Barbosa, Jaciana Marlova Gonçalves Araujo, Mariane Lopez Molina, Pedro San Martin, Jean Pierre Oses, Karen Jansen, Luciano Dias de Mattos Souza, and Ricardo Azevedo da Silva. “Pro-Inflammatory Cytokines and Psychotherapy in Depression: Results from a Randomized Clinical Trial.” Journal of Psychiatric Research 75 (April 2016): 57–64.
Pan, Ying, Xu-Yang Chen, Qing-Yu Zhang, and Ling-Dong Kong. “Microglial NLRP3 Inflammasome Activation Mediates IL-1β-Related Inflammation in Prefrontal Cortex of Depressive Rats.” Brain, Behavior, and Immunity 41 (October 2014): 90–100.
Jacka, Felice N., Adrienne O’Neil, Rachelle Opie, Catherine Itsiopoulos, Sue Cotton, Mohammedreza Mohebbi, David Castle, et al. “A Randomised Controlled Trial of Dietary Improvement for Adults with Major Depression (the ‘SMILES’ Trial).” BMC Medicine 15, no. 1 (January 30, 2017): 23.