How the Microbiome in Early Life Shapes the Immune System

From the time of your birth, your microbiome – the trillions of microbes living on and inside a person – begins taking shape, and by around two to three years of age becomes established for life. During the first few years, especially the first few months, of life, environmental factors can influence the microbiome’s composition. In a review article published in Science, investigators from BWH describe evidence from several studies about factors that can shape the microbiome in early life and influence a person’s immune system, including the later development of inflammatory bowel disease, asthma and allergy.

Human and animal studies have found that some of the factors that may influence the microbiome include circumstances surrounding birth (e.g. delivery by cesarean section), exposure to antibiotics, diet and more. Evidence from animal studies suggests that the presence or absence of specific microbiota may influence the way the immune system in the lung, intestines or other mucosal tissue develops. The authors also note that observational studies have found that children who grew up on or around farms have a decreased risk for the development of allergic diseases, and that farming exposure during pregnancy may protect an unborn child from asthma.

“A ‘window of opportunity’ that is essential for the proper education of the immune system during early life exists in mice. We believe such a window of opportunity may exist in humans as well,” said corresponding author Richard Blumberg, MD, chief of the Division of Gastroenterology, Hepatology and Endoscopy. “In mice, if the interaction between the microbiome and immune system occurs in a normal manner, the immune system is established in a way that may resist disease. If this proves to be true in humans as well, then carefully examining the influence of factors like exposure early in life to antibiotics (which could disrupt the microbiota) may have important implications in understanding and potentially preventing some autoimmune diseases.”

Paper cited: Gensollen T et al. “How colonization by microbiota in early life shapes the immune system.” Science DOI: 10.1126/science.aad9378

Microbial Cooperation in the Intestine

The human intestine is home to a dense and diverse ecosystem of microbes, but little is known about how the abundant bacteria in our gut interact with each other. In a new study published in Nature this week, Brigham and Women’s Hospital (BWH) investigators, in collaboration with colleagues at Boston Children’s Hospital, report on a rare example of cooperation between different species of bacteria.

The team found that one species of bacteria, Bacteroides ovatus, digests a dietary polysaccharide – a complex carbohydrate – at a cost to itself but at a benefit to another species. Using in vitro experiments and a mouse model, the team found that B. ovatus receives reciprocal benefits from other gut species in return.

“Finding a predominant member of our microbiota that doesn’t need to digest a dietary sugar in order to use it for itself, but that seems to be doing so to feed another species of bacteria was a big surprise,” said lead author Seth Rakoff-Nahoum, MD PhD, of Boston Children’s Hospital’s Division of Infectious Diseases.

“Such interspecies cooperative interactions are rarely described, especially among the abundant bacteria in our intestines,” said senior author Laurie Comstock, PhD, of BWH’s Division of Infectious Diseases.

Kevin Foster of Oxford University also contributed to this work.

Paper cited: Rakoff-Nahoum S et al. “The evolution of cooperation within the gut microbiota” Nature DOI: 10.1038/nature17626

Seven Emergency General Surgical Procedures Account for 80 Percent of Complications, Deaths and Costs

A team of researchers led by Joaquim M. Havens, MD, at the Center for Surgery and Public Health at BWH has found that seven procedures account for about 80 percent of all admissions, deaths, complications and inpatient costs attributable to operative emergency general surgery (EGS) in the U.S. The study was published in JAMA Surgery.

These seven procedures include: partial colectomy (removal of part of the colon), small-bowel resection, cholecystectomy (removal of gall bladder), operative management of peptic ulcer disease, removal of peritoneal (abdominal) adhesions, appendectomy and laparotomy (an operation to open the abdomen).

“Our goal was to identify a standardized, representative set of procedures that make up the bulk of the national clinical burden of EGS, which could be used to establish benchmarks, guide focused research priorities and inform quality improvement programs,” said Havens.

EGS encompasses the care of the most acutely ill, highest risk and most costly general surgery patients. There are more than 3 million patients admitted to U.S. hospitals each year for EGS diagnoses.

Study authors reviewed data from the 2008 to2011 Hospital Cost and Utilization Project’s (HCUP) National Inpatient Sample. Adults with primary EGS diagnoses consistent with the American Association for the Surgery of Trauma definition, admitted urgently or emergently, who underwent an operative procedure within two days of admission were included in the analyses. Procedures were ranked to account for national mortality and complication burden. Among ranked procedures, contributions to total EGS frequency, mortality, and hospital costs were assessed.

The study identified 421,476 patient encounters associated with operative EGS, weighted to represent 2.1 million nationally over the 4-year study period. The overall mortality rate was 1.2 percent, the complication rate was 15 percent and average cost per admission was $13,241. After ranking the 35 procedure groups by contribution to EGS mortality and morbidity burden, the final set of seven operative EGS procedures were identified, which collectively accounted for 80 percent of procedures, 80 percent of deaths, 79 percent of complications, and 80 percent of inpatient costs nationwide.

“National quality benchmarks and cost reduction efforts should focus on these common, complicated, and costly EGS procedures,” the authors wrote.

Paper cited: Scott J.W. et al. “Use of National Burden to Define Operative Emergency General Surgery,” JAMA Surgery. Published online April 27, 2016. doi:10.1001/jamasurg.2016.0480.