By Kim E. Barrett, Division of Gastroenterology, Department of Medicine, University of California, San Diego, USA, @Jphysiol_eic.
This article originally appeared in our magazine, Physiology News.
We all know that stress has an impact on the function of our digestive system. Whether it is the transient butterflies that accompany an exam or an interview, or the more toxic consequences of chronic stress, our experience of our world and its challenges can profoundly alter our digestion, absorption of nutrients, and excretion.
What has been less fully appreciated, until recently, is that communication between the brain and gut is bi-directional. Gut illnesses may be accompanied by brain disorders, such as anxiety, depression, and memory problems. The brain and spinal cord are in constant communication with the gut, in part via the “little brain” – the nerves present in the gut that communicate with the brain.
While we humans like to think that we are masters of our own universe, in fact we, along with all other beings, are superorganisms. Our bodies consist not only of our own cells and genome, but also of distinctive populations of ‘friendly microbes’, along with their genes and ability to break down compounds. This so-called “microbiome” is made up mostly of bacteria, the best-studied populations, but also other microbes such as fungi and viruses (which are only now beginning to be examined). Specialized groups of microbes inhabit various parts of our body, such as the intestines, mouth, skin, lungs, and genitals. The most extensively characterized of these microbiomes is the collection of bacteria in the gut, consisting of thousands of species in a typical healthy human adult. They reside throughout the intestines, but are most heavily concentrated in the colon. There are as many as 1014 of them throughout the gut. That’s ten times the number of human cells in the entire body (Sekirov et al., 2010). Recently, the 10:1 ratio has been disputed, with a claim that the numbers of human cells and gut bacteria are of the same order of magnitude (Sender et al., 2016). Even if this true, the microbes collectively have more genes than our cells do.
We are rapidly learning the ways in which these gut microbes may be important mediators of the cross-talk between the gut and brain. They are, in turn, influenced by environmental conditions, such as stress and diet, in ways that change their impact on both our thinking and digestion.
Friendly microbes – what do they do for us?
Microbes, in the gut or elsewhere, are not essential for life, as illustrated by the ability to raise animals in a sterile environment in the lab. Nevertheless, the gut microbes in particular offer several advantages to the organism they inhabit. For us, they break down nutrients we can’t, such as dietary fibre, drugs, carcinogens, and compounds that break down into vitamins. Similarly, the microbiota “educate” the immune system of organs such as our lungs and intestines to fight foreign substances but tolerate the proteins of broken-down food or other harmless microbes.
The organisms of the microbiome also defend against pathogens by crowding them out, producing substances that kill bacteria or keep them from reproducing, or causing the host to create those lethal compounds itself. For this reason, antibiotics that kill beneficial microbes can render patients susceptible to intestinal infections and overgrowth of harmful bacteria, such as Clostridium difficile (C. diff).
Gut microbes and birth
We think that gut microbes exist in the body immediately after birth, although some controversial data suggests the presence of microbes in the fetus before birth. Animals without microbes can be born via Caesarean section (C-section), implying that even if there are microbes in the womb, organisms don’t need them to survive (Perez-Munoz et al., 2017).
For babies delivered vaginally, their gut microbes are initially very similar to the mother’s vaginal microbiota, whereas they differ substantially for babies delivered by C-section. An intriguing recent study partially restored “normal” microbes in the gut, mouth, and skin by exposing babies delivered via C-section to the mother’s vaginal fluids. The authors thought that this might reverse the known association between C-section deliveries and an increased risk for immune and metabolic disorders (Dominguez-Bello et al., 2016).
For the first year or two of life, the baby’s microbes are relatively simple and variable, but they gradually take on the characteristics of a mature, adult-like microbiome. These early years are also a critical period for maturation of the immune system, so it makes sense that disrupting the maturation of the infant’s microbes also predisposes them to autoimmune and allergic diseases. For example, the increasing tendency to protect babies from germs or an excessive early-life use of antibiotics may set them up for an increased later risk of asthma, metabolic disease or obesity. This is called the “hygiene hypothesis” (Schulfer & Blaser, 2015).
Stay tuned for the part 2 of the series next week to learn about how gut microbes respond to stress, and the efficacy of therapeutics, from probiotics to transplants.
Dominguez-Bello MG, De Jesus-Laboy KM, Shen N, Cox LM, Amir A, Gonzalez A, Bokulich NA, Song SJ, Hoashi M, Rivera-Vinas JI, Mendez K, Knight R & Clemente JC. (2016). Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat Med 22, 250-253.
Perez-Munoz ME, Arrieta MC, Ramer-Tait AE & Walter J. (2017). A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome 5, 48.
Schulfer A & Blaser MJ. (2015). Risks of antibiotic exposures early in life on the developing microbiome. PLoS Pathog 11, e1004903.
Sekirov I, Russell SL, Antunes LC & Finlay BB. (2010). Gut microbiota in health and disease. Physiological reviews 90, 859-904.