“We’re only just beginning to understand how microbial activities influence cell types and ultimately the health of the host.” - Susan Lynch, PhD
Could the trillions of microbes that live in and on our bodies be the piece of the biomedicine puzzle we’ve been missing? The role of the human microbiome – the vast ecosystem of bacteria, viruses, fungi, and other infinitesimally small organisms that live on our skin and in our mouths, guts, and respiratory and urogenital tracts – is one of the great, unexplored frontiers of human biology. Scientists still have much to learn, but they are already developing treatments, such as microbial transplants that show promise for addressing infectious, chronic inflammatory, and even neurological diseases.
Susan Lynch, PhD, head of the UCSF Benioff Center for Microbiome Medicine, has been fascinated by the human microbiome since the field emerged just 15 years ago. “We thought for a long time that microbes simply help us digest foods, but it turns out that the range of genes encoded by the human microbiome is far greater than previously thought, resulting in a huge diversity of microbial-derived molecules,” says Lynch. “We’re only just beginning to understand how these microbial activities influence cell types and ultimately the health of the host.”
Unraveling the mysteries of the human microbiome and its impact on our health requires contributions from many specialists, from epidemiologists and immunologists to microbiologists and geneticists. The organisms and genes present or absent in any one human microbial community are influenced by a multitude of factors, including the way we were birthed, where we live, who we live with, the pets we own, the air we breathe, the food we eat, and the drugs we take.
“It’s incredibly complicated,” says UCSF epidemiologist Katie Pollard, PhD, who identifies patterns and themes across microbial communities in healthy and unhealthy people. She describes her work of tracking bacterial strains and their genes using sequencing methods, algorithms, and big data tools as a “huge, messy bioinformatics problem.”
Pollard and Lynch, along with many others in the field, believe that studying the early-life microbiome can provide some crucial clues. “Babies are born with an extremely simple microbiome in their meconium – their first bowel movement,” explains Lynch. “But by age 3, children have developed a microbiome that is as diverse as that of an adult’s yet very distinct in terms of the role it plays.” Lynch posits that altering the microbiome of certain at-risk subjects early in life might prevent disease further down the road. Lynch’s lab already has found a connection between the neonatal gut microbiome and a child’s propensity for allergies and asthma.
Following the same logic, UCSF dermatologist Tiffany Scharschmidt, MD, is deciphering the molecular basis of how microbes shape the immune function in relation to skin diseases. Her lab uses animal models to map the dialogue between the immune system and the microbiome. Scharschmidt’s research has revealed that microbes colonizing hair follicles very early in life might influence the immune response on the skin – and therefore a child’s susceptibility to skin disorders.
“Sue [Lynch] is close to determining what might be an optimal microbiome to stave off allergy,” says Scharschmidt. “I believe the same concepts apply with inflammatory skin diseases, like eczema and acne.”
Other scientists seek to comprehend the effects that drug treatments have on the gut microbiome for conditions including cancer, rheumatoid arthritis, and other autoimmune diseases. For example, a groundbreaking study published in Science, co-authored by UCSF microbiologist Peter Turnbaugh, PhD, revealed that the efficacy of levodopa, a therapy used to reduce tremors in patients with Parkinson’s disease, might be dependent on an enzyme in the gut microbiome.
“We’re really interested in the interaction between drugs and the microbiome and how variations in microbial communities might explain why people respond differently to a medication,” says Turnbaugh.
Technological advances in data science, sequencing, and mass spectrometry enable these pioneering investigators to examine not only the species of microbes in the human microbiome but also the genetic diversity of the species and the physiological effects of the molecules that they produce. The holy grail will be figuring out how to manipulate the microbiome and create new molecular environments that are health-promoting.
The UCSF Benioff Center for Microbiome Medicine, made possible by a $25 million gift from Marc and Lynne Benioff in 2019, aims to drive these innovations in microbiome-based therapies through support for new faculty members, expanded technological infrastructure, and translational collaborations between microbiome and clinical researchers across the university.
“What really excites me about doing this now at UCSF is that we have all the pieces in place,” Lynch says. “We have the computational capacity and expertise to work with big data, the immunological and microbiological skills to profile human immunity, and the technology to study the microbiome at very high resolution. The marriage of these three pieces will accelerate breakthrough discoveries and improve human health.”