Systems biology is an inter-disciplinary field of study which is based on a holistic “understanding that the whole is greater than the sum of the parts”, according to Seattle-based Institute of Systems Biology, and combines bioinformatics, biology, computer science, engineering, physics and more to predict how systems will change over time. The discipline is attracting a lot of attention (and investment).
Speaking at the recent 4th annual Thought Leaders Consortium hosted by the Personalized Lifestyle Medicine Institute in Phoenix, AZ, Dr Knight explained that we have about 20,000 human genes, but we carry around 2-20 million microbial genes, so we’re about 1% human.
“It’s hard to do systems biology when you ignore 99% of us, and that’s what we’re doing when we ignore the microbiome,” said Dr Knight.
And this is important because the microbiome has been linked to an ever-growing number of health benefits, from the well-established gut health and immune function to cardiovascular health, inflammation, brain health and mood, oral health, and more.
Gut microbiota and obesity
One of the most intriguing and potentially important areas of research is in obesity. “I can tell you with 90% certainty if you’re lean or obese based on your microbiome,” noted Dr Knight. “If I was going on human genes alone, the accuracy would be 57%.”
“We’ve been losing microbes over the years through a combination of antibiotics, hygiene and also diet. The processing applied to this food has stripped out much of the good stuff and replaced it with synthetic analogues,” he said.
Dr Knight cited work by Jeffrey Gordon and his group at Washington University in St. Louis, which reported that microbial populations in the gut are different between obese and lean people, and that when the obese people lost weight their microflora reverted back to that observed in a lean person, suggesting that obesity may have a microbial component (Nature, Vol. 444, pp. 1022-1023, 1027-1031).
Dr Knight contributed to a 2013 paper in Science (Vol. 341, Issue 6150), also led by Prof Gordon, which found that transplanting gut bacteria from obese humans into germ-free mice leads to greater weight gain and fat accumulation than mice that were given bacteria from the guts of lean humans.
The findings showed that weight and fat gain is influenced by communities of microbes in the gut and their effect on the physical and metabolic traits of the host, leading to metabolic changes in the rodents that are associated with obesity in humans.
“We shouldn’t be looking for a solution to the obesity epidemic in human genes,” said Dr Knight, before adding that a fascinating correlation exists between the prevalence of antibiotic prescription in the US and the prevalence of obesity (see figure below). “Modifying the microbiome may be responsible,” he said.
Anecdotal evidence supports such associations, with people reporting that aspects of their weight, or aspects of their personality have changed after antibiotics. Animal data from researchers at McMaster University has also indicated that changing the microbiota can change behavior, with timid mice becoming brave as a result of microbiota modification (Gastroenterology, 2011, Vol. 141, No. 2, pp. 599-609).
“Despite tremendous advances in the field of nutrition much of the impact is disappointingly small at a population level,” said Dr Knight. However, effects at an individual level can be significant but a lot of variability, he said.
And with this he pointed to a “remarkable study” published in the journal Cell by Zeevi et al., (2015, Vol. 163, No. 5, pp 1079-1094), which found that “personalized diets may successfully modify elevated postprandial blood glucose and its metabolic consequences”. (This study led to the personalized nutrition company Day Two – for more information about this, please watch the video below).
American Gut Project
Dr Knight co-launched the American Gut Project with Jeff Leach over Thanksgiving in 2012, and is designed to let everyone know what’s in your microbiome: it’s the world’s largest crowd-funded citizen science project in existence, and has so far raised over $1 million, with samples collected from over 10,000 people.
“With the data from this we can link microbiome to all kinds of different things. For example, age, IBD or antibiotics have fairly large effects, but we’re also seeing effects of sleep on microbiota,” said Dr Knight.
The project is now expanding into other populations, including Britain.