Antibiotic use alters microbiome, increasing risk for obesity, diabetes

ORLANDO, Fla. — The increasing reliance on antibiotics in pregnancy and early childhood is influencing long-term physiology through microbiotic changes, altering key “conversations” with stem cell populations and guiding early cellular development of adipocytes, immunocytes, muscle and bone, according to a speaker here.

“The microbiome in early life is a critical determinant of normal human metabolic and immunological development,” Martin J. Blaser, MD, director of the human microbiome program and professor of microbiology at the NYU School of Medicine told Endocrine Today. “We have been substantially impacting the early life microbiota through such practices as the extensive use of antibiotics and C-sections. Work in animal models show that antibiotic impacts that change the microbiome have effects on host tissues, which affect disease outcomes, including obesity and type 1 diabetes.”

Diseases like obesity have grown rapidly in recent decades, Blaser noted: In 1989, there was no state in the U.S. where more than 14% of adults were obese. By 2010, there was no state where less than 20% of adults had obesity.

“This is happening everywhere, and the distance between the first map and the last map is only 21 years,” Blaser said, speaking during the presidential plenary session at ENDO 2017. “This is also happening all over the world. So, where might this be coming from?”

Over generations, changes in the ancient relationships between microbes and their human hosts have likely played a key role in diseases seen today, Blaser said. Humans begin life in a sterile womb, and babies historically have been exposed to microbes as they descend the birth canal of the mother and through their mother’s breast milk, forming the foundation of the GI tract.

“But now, moms are not the same as they used to be,” Blaser said. “They live in an environment with antisepsis. They’ve taken antibiotics, often during pregnancy, before the intergenerational transfer. They have a diet with antibacterial substances. And babies aren’t the same either. They may be born by Caesarean section and miss that passage through the birth canal. Babies are bathed extensively, they have formula that only superficially resembles breast milk, and, of course, they get a lot of antibiotics.”

‘Disappearing microbiota’

Based on these ideas, Blaser said, he has proposed what he calls the “disappearing microbiota hypothesis.”

“This hypothesis has two major tenets,” Blaser said. “First, the changed human ecology has altered the transmission and maintenance of our ancestral microbes, and this affects the composition of the microbiota. Second, especially important are microbes usually acquired in life, since they affect a developmentally critical stage.”

Both human and animal studies have shown a loss of microbiota diversity may be directly influenced using antibiotics, Blaser said.

“Antibiotics are miraculous drugs, but we have been using them more and more,” Blaser said. “According to [WHO], 73 billion antibiotic doses worldwide yearly. That’s 10 doses for every man women and child on earth. In the U.S., according to CDC, 258 million courses a year. That’s 833 per 1,000 — five courses for every six people; [for] children, almost three courses [of antibiotics] by the time they are age 2 years. More than 50% of pregnant women are getting antibiotics during pregnancy.”

Recent studies also suggest that greater antibiotic use early in life is associated with greater adiposity in children, though Blaser cautioned that the data are mostly observational. Blaser also pointed to famers, who often feed their livestock sub-therapeutic antibiotic doses (often referred to as STAT) to help their animals gain weight. Experiments in mice fed antibiotics in early life showed they had a fecal community structure that differed from mice unexposed antibiotics.

Reversing course

In this next generation, Blaser said, humans can make important choices that can either spur a further decline in microbiota, arrest the decline or reverse the trend through restorative steps.

“The pediatricians of the future will be examining babies, and they’ll be examining babies’ diapers,” Blaser said. “And they will ask, ‘Does this baby have the global microbes that all babies should have? Does this baby have the personal microbes that a baby of their genotype has?’ If they don’t, they’re going to administer those microbes to the baby and analyze, is this working? This, I believe is one component of what the future of medicine will look like. It will take some time, but that will be the direction.”

“We need to define the parameters more fully, but the evidence is sufficient to begin to influence both physician and patient choices,” Blaser said in an interview. – by Regina Schaffer

Reference:

Blaser MJ. Early Life Microbiota and Physiologic Development. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2017; Orlando, Fla.

Disclosures: Blaser reports no relevant financial disclosures.