News: Modern Life Means Less Gut Bacteria, More Chronic Disease

When you have an infection, a doctor prescribes antibiotics to make the bacteria that causes it disappear. Sounds like a good idea, but the disappearance of microorganisms that have inhabited humans for millennia could be driving rising numbers of serious illness and debilitating conditions.

Martin J. Blaser is the Director of the Human Microbiome Program at the NYU School of Medicine. A commentary written by Blaser in the journal Nature Reviews Immunology, suggests that loss of microbes that have long accompanied humans is causing an overall rise in conditions against which our bodies can no longer defend.

Even as medical research makes stunning progress on certain infectious and other diseases, case numbers on others continue to tick upward. Some of the illnesses or disorders mentioned in this paper as possibly being microbiome-mediated include Type 1 diabetes, autism, inflammatory bowel disease, food allergies, and more. Each of these conditions is complex in its causes and triggers — there is still so much that we do not know.

In the broader view, Blaser offers a theory that "losses of particular bacterial species of our ancestral microbiota have altered the context in which immunological, metabolic and cognitive development occur in early life, which results in increased disease." This important idea takes into account how modern life is impacting the loss of important microbes that could be responsible for our well-being, physically and psychologically.

The Importance of Microbiota in Early Life

The bacterial communities that normally reside on and in humans have been developing as long as we have. The biological imperative of any species is to grow and reproduce, and our microbiota has both enjoyed and contributed to our success at the seeming top of the food chain.

In his commentary, Blaser notes early life is critical for humans to gain exposure to, and establish, important communities of microbiota in order to aid our immune system in important early life tasks that include:

• Understanding what is self and not self: This puzzling comment refers to the critical ability of our immune system to see, meet, and identify other parts of its own host as "safe" and not as invaders. The loss of the ability of your immune system to understand what is you, and what is enemy, is at the root of autoimmune diseases. Autoimmune diseases occur when the immune system fails to recognize its own cells are not the enemy, and mounts an often lifelong attack on itself.
• Metabolism: Early in life, through breastfeeding and seeding of the gut microbiota at birth, your body gains an understanding of how much energy to "partition" and how much to expend and save. Problems establishing these processes may come into play in later life as a contributor to obesity.
• Brain function: In infancy, and throughout life, connections between the gut microbiome and the brain support function, and can also lead to dysfunction, including potential involvement in autism spectrum disorders.

Microbial diversity and abundance is our birth inheritance. During pregnancy, birth, and breastfeeding, essential communities of microbiota flow to our bodies though a process called "vertical transmission." This means the passage of ancestral and local microbes from a mother to her child.

In our day, that inheritance is being interrupted in several ways including:

Caesarean section: According to the commentary, one-third of births in the US are now surgical. While birth teams are beginning to initiate the practice of swabbing C-section babies with vaginal secretions taken from the mother, it is too early to tell if this attempt to replace the seeding of the child with the mother's microbiome is effective n the longer term. Blaser notes that during C-section, "intergenerational transfer of microorganism(s), which is a conserved feature of essentially all animals, is diminished."

Use of antibiotics during pregnancy: The use of some antibiotics during pregnancy has become commonplace, disturbing the microbiome of the mother, and the altered bacterial communities she passes to her child. Recent studies have discussed that some antibiotics given to pregnant women put children at higher risk for birth defects.

Lack of breastfeeding: Human breast milk is the critical food for human infants. Biologically active, and fine-tuned on site, no formula or supplement can replace the microbial richness lost when a baby is not given access to the breast milk of its mother. Breast milk both seeds and maintains the infant microbiota until it can do so itself. While some women are unable to produce enough breastmilk, still others suffer a lack of social support for breastfeeding in the workplace, or in public. In a society that pushes infant formula — the overall biological loss in early life is great and could impact adult immune and other functions.

Because the microbiome of an infant is not well-established, interruptions of the seeding of baby bodies with ancestral microbiota can last a lifetime. The common use of antibiotics has not only supported the creation of drug-resistant bacteria but killed off bacteria in our bodies that perform important roles as supporters and mediators of our immune system. Blaser writes: "In young children in particular, (antibiotic) insults may change the development of the 'adult' microbiota, and not allow its normal maturation."

As our lives become more sanitary, there is also a loss of horizontal transmission of bacteria. Children do not play as they used to, and are less exposed to what might have been considered harmless microbes. This does have its advantages when it comes to cleaner drinking water and fewer pathogens on our food. Some of the bacteria we do pick up could be more dangerous given the loss of normal, harmless bacteria on our skin due to our overuse use of antibiotic soaps and disinfectants.

The real loss suggested by Blaser is the damage to our innate and adaptive immune system on which we depend to protect us 24/7 for as long as we live. He writes:

A growing body of evidence indicates that both the prenatal (maternal) microbiota and the early life (infant) microbiota have crucial roles in the later development of adaptive immunity. Important interactions between innate and adaptive immunity may also be relevant here. With the decline of the ancestral microbiota, the net early life interactions with innate immune elements may have shifted away from the commensal taxa. Thus, the signals that the major adaptive immune cells receive from their two principal inputs — the microbiota and innate immune cells — will have shifted, creating an altered context for their next developmental steps.

Noting the reduction in the content and context of our microbiota and our immune adaptivity, Blaser predicts stronger, starker responses from "opportunistic organisms and adventitious stimuli." Simply put, that means the greater onset of disease at all stages of life.

Blaser highlights the need for more information on developmental windows in which the microbiome is established, disturbed, and restored — if ever. He advises solutions to repair the human microbiome may include:

• Developing best practices for nurturing the human microbiome
• Create drugs, prebiotics, "validated probiotics," or vaccines
• Develop ways to suppress opportunistic pathogens and nurture beneficial microbiota

To restore the human microbiome, Blaser believes immunologists of present-day will need to revisit the roots of nineteenth-century microbiology to uncover and recover, what they can. Blaser said, "I believe that ultimately we will have to restore our lost microbiota to optimize human health and to reverse the disease epidemics that are increasing around the world."

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