The human body is not just an organism, it’s an ecosystem. To the billions of microscopic bacteria, viruses and fungi living in the various nooks and crannies of our intestines, mouth, nose, and other areas, we are the world, the environment that drives their evolution. Though scientists and physicians have long known that humans are housing projects for a wide array of species, research on the clinical impact that microscopic population exerts upon its host is just starting to establish momentum. Many researchers are now exploring links between what’s become known as the “microbiome” and everything from infectious disease to diabetes and obesity to psychiatric disorders.
An official seal of approval was stamped on to these efforts by the National Institutes of Health in 2008, with the announcement of the $157 million “Human Microbiome Project.” Tuesday, the project was given another $42 million bolus of funding, $1.1 million of which went to a team of University of Chicago and Argonne National Laboratory scientists. But research into the microbiome is already yielding interesting results on the world inside your gut, and how it is affected by diet from the very start of life.
The debate over giving babies breast milk or formula has swung like a pendulum since the mid-20th-century, with medical societies now endorsing breastfeeding infants whenever possible. Studies have shown that breastfeeding has advantages in protecting infants from infection and disease and provides essential, easily-digestible nutrients. But what is the biological basis for breast milk’s superiority? Scientists have speculated that it has to do with the effect of diet on the microbes of the gut. In a paper published last month at PLoS ONE, Michael Morowitz, assistant professor of surgery and pediatrics at Comer Children’s Hospital, sought to test that hypothesis with the latest genetic technology.
Morowitz was drawn from surgery to microbiology after witnessing the damage caused by a frightening infant disease: neonatal necrotizing enterocolitis (NEC). Seen often in premature babies, NEC causes intestinal inflammation that can require surgical removal and may lead to lifelong complications or death. As the surgeon on such procedures, Morowitz said he became interested in ongoing research on how to reduce the number of NEC cases.
“You say to yourself, ‘How can you prevent it?’ The literature tells you there aren’t many ways other than supporting breast milk usage,” Morowitz said. Others had proposed a link between breast milk, gut bacteria, and protection against NEC, but until recently the technology did not exist to take a full census of the microbial world, he said.
For the PLoS ONE paper, Morowitz and his team decided to study the effects of breast-milk versus formula on the microbe population in the intestines of piglets. By recording a “transcriptome” – a snapshot of gene expression – from the intestinal fluid of the piglets, Morowitz’s team could detect which bacterial species were present and active in the two groups.
Comparing the bacterial census from formula-fed and breastmilk-fed piglets yielded more similarities than differences, but the places where the two microbiomes didn’t line up presented some interesting possibilities. Genes involved in the metabolism of amino acids, the building blocks of proteins, were more abundant in breastmilk-fed compared to formula-fed animals. Metabolizing one amino acid in particular, called arginine, has been linked to the risk of contracting NEC, Morowitz said.
The comparison also found an increase in genes related to antioxidant activity, a healthy process often claimed as an advantage of breast milk – “I think that this lends some support to the idea that some of the antioxidant power of breast milk comes not from the milk itself but from organisms that are in the gut,” Morowitz said. But other assumptions about breast milk were disproved; healthy “probiotic” bacterial species appeared in equal numbers in the two populations, contradicting a long-held assertion about breast milk.
It’s unclear how applicable the results in piglets might be to the gut microbiomes of human infants, Morowitz cautioned. But the success of the advanced sequencing technologies used in piglets suggests that they could be used in human studies, with stool samples instead of intestinal fluid. Until those studies are done, the subtle but biologically intriguing differences between the effects of breastmilk and formula are a reminder that a diet’s influence runs deep.
“When parents or clinicans tend to talk about diet, whether it’s for a baby or an adult, you tend to think of the effects of diet on the human body,” Morowitz said. “But an incredibly important point that we all need to understand is that what we eat very markedly impacts the bacterial communities in the gut – both which organisms are present and which genes they are induced to express.”
“So one of our big messages in our lab is that dietary intake feeds two groups: not only humans, but also their bacteria.”
Poroyko V, White JR, Wang M, Donovan S, Alverdy J, Liu DC, & Morowitz MJ (2010). Gut microbial gene expression in mother-fed and formula-fed piglets. PloS one, 5 (8) PMID: 20805981