Modern medicine was founded on the discovery that microorganisms are a cause of disease. It has taken several hundred years to begin to realize that they also can be beneficial to our health, Stanford University Professor David Relman, M.D, told a symposium at the AAAS Annual Meeting.

Humans have evolved a symbiotic, co-dependent relationship with specialized communities of microorganisms that colonize every part of the our bodies, from the space between our toes, to the roof of our mouths and the recesses of our gut. They are part of “what it means to be human,” Relman said.

These organisms break down foods that the body cannot; protect against infection; and release signaling molecules that our bodies have become accustomed to as part of healthy homeostasis.  Now researchers are exploring whether conditions such as autism and Type II diabetes may be the result of disruptions in the normal ecology of the gut.

Relman’s lab has led the way in characterizing gut microbiota and how it can vary by geography, diet, and with age, among other factors.

Recent work has evaluated the impact of administering the antibiotic ciprofloxacin, commonly known as Cipro. It immediately reduces the gut bacteria count by a third to half. But more surprising is the lasting effect once the drug is stopped. While some bacteria rebound quickly to baseline,  others see only partial recovery. The change in the number and diversity of gut microorganisms “might be semi-permanent,” said Relman.

There also is the suggestion that subsequent exposure to Cipro results in more persistent change. “You could say that the [microbial] community had memory of the first time,” he said.

Professor Jeremy Nicholson, from Imperial College, London, said: “There is a complex interaction between the [host] gene environment and the microbes, they all impact on each other.” Changing the ratios of microbes can dramatically affect the metabolism of food, not just in the gut but also in the liver, kidney, and heart.

He noted that human genetic activity can produce 700-800 different metabolites—but  the microbiota in the gut can produce “thousands and thousands” of different metabolites, or chemical compounds necessary for normal functioning. “There may be 50 times the number of druggable targets in the microbiome as there is in the human genome” that might be exploited to improve health.  

Nicholson pointed to the example of bariatric surgery, such as gastric bypass or gastric banding, “where you are changing the whole physiological-biochemical relationship scale” by drastically reducing the size of the stomach. Interestingly, “80% of the people with type 2 diabetes are cured the following day by this procedure,” Nicholson said. He believes microbes probably are an important causal factor—when the stomach is physically reduced, so too are gut microbes.

“If you can find the biochemistry root of all this,” he said, then you don’t need the actual bariatric surgery any more.”

Autism is another focus of Nicholson’s work. About 70% of persons with autism have serious gastrointestinal disorders at some point in their lives. Other researchers have shown they also have “a very unusual gut microbiome,” he told the AAAS audience.  

He said the human microbiome changes very rapidly in the first 2-3 years of life. “You don’t get an adult microbiome until you are about 3 years old. So if you do something that changes that in some ways, so that you get bugs that are potentially hostile, you can generate potentially a whole series of diseases from that.”

“In the case of autism, your neurological connections, your synaptic connections, are being made in the first 2-3 years of life. It is easy to imagine—this is purely speculation—how a microbe might be introduced that generates neurotoxins at the time you are doing synaptic development. That has got to be bad news. It is just a possible explanation.”

Immune function is another changing factor exerting pressure on the microbiome. “There is an incredible connection between mother and microbes,” he said. The mother’s immune system protects the developing fetus. Those antibodies linger for at least six months after delivery as the infant’s immune system develops.

The infant’s microbiome is “seeded” from the mother by exposure at time of delivery, and subsequently through breast feeding, which also continues to transfer some maternal antibodies.

“The other thing that is a very big worry is antibiotics in early childhood development because that could possibly derail the ecology,” Nicholson said. “[When] the system is developing, it must be much easier to derange.”

For Nicholson, it is an area that needs to be looked at very carefully.