Could Manipulating the Microbiome Treat Food Allergies?

University of Chicago immunologist Cathryn Nagler began to suspect that the body’s resident bacteria play a role in food allergies almost two decades ago. A handful of studies of germfree mice in the 1980s and ’90s had suggested that bacteria in the gut, or compounds they produce, such as lipopolysaccharide (LPS), are important in teaching the immune system not to overreact to the foods we eat. But it was a new mouse model of peanut allergy, developed by researchers at Mount Sinai School of Medicine in New York in 2000, that really made Nagler think about whether the gut microbiome might be involved in how humans respond to dietary antigens.

The mouse strain they used, C3H/HeJ, carried a mutation in the toll-like receptor 4 (TLR4). This protein had recently been shown to mediate immune responses triggered by a bacterial antigen known as lipopolysaccharide (LPS), and the mutant mice were consequently nonresponsive to LPS. But according to the 2000 paper, the animals also exhibited anaphylaxis—a sometimes fatal allergic reaction in people—upon exposure to freshly ground peanuts.

It made Nagler wonder if TLR4—and specifically, the propensity of certain gut bacteria to activate it—was the key to tolerance to dietary antigens. Sure enough, when she treated mice with broad-spectrum antibiotics to deplete their intestinal bacteria, even animals with wildtype TLR4 had severe reactions to food allergens. “That established a role of signaling by bacteria in the gut in regulating responses to food,” she says. “And then all of the studies we’ve done since then, over 15 years, have built on that.”

These days, there is little doubt that the body’s resident bacteria have a big say in how the immune system responds to food allergens. Research into the underlying causes of food allergies has blossomed to parallel the condition’s growing prevalence: an estimated 6 percent of children and up to 10 percent of adults in the US have an allergy to some food. Scientists have identified connections between a person’s microbial makeup and whether or not that person has a food allergy. Microbiome differences also help determine which children will outgrow their food allergies and which won’t, notes Supinda Bunyavanich, a physician scientist at Icahn School of Medicine at Mount Sinai. “So it suggests that there is an impact of these microbiota on the clinical outcomes.”

Further research in mice has demonstrated a causal relationship between the microbiome and allergic reactions to food. In January, Nagler and her colleagues published the results of an experiment in which they transferred fecal samples from healthy human infants and from infants with cow’s milk allergy to germfree mice. Control animals that did not receive a fecal transplant, as well as mice that received samples from the allergic babies, became sensitized to the milk protein β-lactoglobulin, developing an allergic response upon repeated exposure to the protein. Mice that had received transplants from healthy infants, on the other hand, tolerated the dietary antigen without any issues.

Exploring the microbiomes of the mice, the researchers identified one particular bacterial species, Anaerostipes caccae, that was significantly reduced in rodents that demonstrated an allergic response to cow’s milk. The team also showed that transferring this species “to germfree mice is sufficient to protect against an allergic response to” cow’s milk, Nagler says.

In June, researchers at Boston Children’s Hospital got similar results with a different allergen in a different mouse model. The team found that transplanting fecal material from healthy human babies into their own mouse model of severe egg allergy protected the animals against anaphylaxis, whereas a transplant of fecal material from babies with food allergies provided no such protection. Moreover, they found that feeding allergic mice a consortium of Clostridium or Bacteroides species or even the single species Subdoligranulum variabile was sufficient to provide protection against egg allergy.

“They’re not exactly the same data, but they seem to be very consistent,” study coauthor Rima Rachid, a clinical researcher at Boston Children’s, says of her results and those of Nagler’s group. “We’re very happy, because the science is being validated.”

The mechanisms underlying the bacteria’s effect on response to food allergens appear to be multifaceted. In Rachid’s recent study, the researchers found that the microbes somehow trigger the formation of a type of regulatory T cell called retinoid-related orphan receptor gamma (RoRγ) T cells. If the investigators removed these T cells from their mouse model, the animals had severe reactions to allergen exposure, even after transplants of the protective bacteria. And a study published in May found that germfree or antibiotic-treated mice develop a different type of regulatory T cell that cause elevated level of immunoglobulin E, an antibody that is known to mediate food-allergic reactions. Other work has pointed to a possible role for basophils, immune cells involved in inflammatory responses, and Nagler says she and her colleagues are still working out the role of TLR4.

While researchers continue to untangle these mechanisms, many scientists already have an eye toward microbiome-manipulating interventions for preventing or treating food allergies. Currently, the standard of care for such conditions simply involves avoiding the culpable antigens and being prepared with an epinephrine autoinjector (EpiPen) and an antihistamine in the event of accidental exposures. Immunotherapy, in which patients are exposed to low, increasing doses of an allergen over time, has recently become an option as well, but it only works for some patients, Rachid notes. “There is really an unmet need here for finding better treatment for food allergy.”

Several clinical trials have tested the effects of probiotic supplementation, with promising but mixed results. “When it comes to probiotics, so far the studies done are not very definitive,” says Rachid. The approach is worth pursuing further, she says, noting that she and her colleagues hope to develop probiotics based on the bacterial species they recently identified as protective against food allergy. At the same time, Rachid is overseeing the first clinical trial for fecal transplant for peanut allergy. “It’s a very interesting approach where you’re trying to change the whole microbiome.” The researchers are currently screening potential trial participants.

“There’s tremendous interest in this,” says Bunyavanich, adding that some of her colleagues have started companies to move such approaches forward. “The fact that food allergies have been rising in recent decades really implores us to try to figure out as much as possible what could be contributing to this.”

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Emergency Room Visit Cost How Much Does an Emergency Room Visit Cost?

 Typical costs:
  • An emergency room visit typically is covered by health insurance. For patients covered by health insurance, out-of-pocket cost for an emergency room visit typically consists of a copay, usually$50-$150 or more, which often is waived if the patient is admitted to the hospital. Depending on the plan, costs might include coinsurance of 10% to 50%.
  • For patients without health insurance, an emergency room visit typically costs from $150-$3,000 or more, depending on the severity of the condition and what diagnostic tests and treatment are performed. In some cases, especially where critical care is required and/or a procedure or surgery is performed, the cost could reach $20,000 or more. For example, at Park Nicollet Methodist Hospital in Minnesota, a low-level emergency room visit, such as for a minor laceration, a skin rash or a minor viral infection, costs about $150; a moderate-level visit, such as for a urinary tract infection with fever or a head injury without neurological symptoms, about $400; and a high-level visit, such as for chest pains that require multiple diagnostic tests or treatments, or severe burns or ingestion of a toxic substance, about $1,000, not including the doctor fees. At Dartmouth-Hitchcock Medical Center[1] , a low-level emergency room visit costs about $220, including hospital charge and doctor fee, with the uninsured discount, while a moderate-level visit costs about $610 and a high-level visit about $1,400.
  • Services, diagnostic tests and laboratory fees add to the final bill. For example, Wooster Community Hospital, in Ohio, charges about $170 for a simple suture, $200 for a complex suture, about $170 for a minor procedure and about $400 for a major procedure, not including doctor fees, medicine or supplies.
  • A doctor fee could add hundreds or thousands of dollars to the final cost. For example, at Grand Lake Health System[2] in Ohio, an emergency room doctor charges about $100 for basic care, such as a wound recheck or simple laceration repair; about $300 for mid-level care, such as treatment of a simple fracture; about $870 for advanced-level care, such as frequent monitoring of vital signs and ordering multiple diagnostic tests, administering sedation or a blood transfusion for a seriously injured or ill patient; and about $1,450 for critical care, such as major trauma care or major burn care that could include chest tube insertion and management of IV medications and ventilator for a patient with a complex, life-threatening condition. At the Kettering Health Network, in Ohio, a low-level visit costs about $350, a high-level visit costs about $2,000 and critical care costs almost$1,700 for the first hour and $460 for each additional half hour; ER procedures or surgeries cost$460-$2,300.
  • According to the U.S. Agency for Healthcare Research and Quality[3] the average emergency room expense in 2008 was $1,265.

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What should be included:
  • According to the U.S. Centers for Disease Control and Prevention, in 2008, about 18%of emergency room patients waited less than 15 minutes to see a doctor, about 37%waited 15 minutes to an hour, about 15% waited one to two hours, about 5% waited two to three hours, about 2% waited three to four hours, and about 1.5% waited four to six hours.
  • In some cases, the doctor might recommend the patient be admitted to the hospital. The American College of Emergency Physicians Foundation offers a guide[4] on what to expect.

Additional costs:

  • An ambulance ride typically costs $400-$1,200 or more, depending on the location and services performed.


  • An urgent care center offers substantial savings for more minor ailments. offers a guide[5] on when to seek urgent care. An urgent care visit typically costs between 20% and 50% of the cost of an emergency room visit. offers a cost-comparison tool for common ailments.
  • Hospitals often offer discounts of up to 50% or more for self-pay/uninsured emergency room patients. For example, Ventura County Medical Center[6] in California offers ER visits, including the doctor fee and emergency room fee but not including lab tests, X-rays or procedures, for $150 for patients up to 200% of the federal poverty level, for $225 for patients between 200% and 500% of the federal poverty level and $350 for patients from 500% to 700% of the federal poverty level.

Shopping for an emergency room visit:

  • The American College of Emergency Physicians Foundation offers a primer[7] on when to go to the emergency room.
  • In most cases, it is recommended to go to the nearest emergency room. The U.S. Department of Health and Human Services offers a hospital-comparison tool[8] that lists hospitals near a chosen zip code.
Material on this page is for informational purposes only and should not be construed as medical advice. Always consult your physician or pharmacist regarding medications or medical procedures.

Needless medical tests not only cost $200 billion, they can do harm

It’s common knowledge in medicine: Doctors routinely order tests on hospital patients that are unnecessary and wasteful. Sutter Health, a giant hospital chain in Northern California, thought it found a simple solution.

The Sacramento-based health system deleted the button physicians used to order repetitive daily blood tests. “We took it out and couldn’t wait to see the data,” said Ann Marie Giusto, a Sutter Health executive.

Alas, the number of orders hardly changed. That’s because the hospital’s medical-records software “has this cool ability to let you save your favorites,” Giusto said at a recent presentation to other hospital executives and physicians. “It had become a habit.”

There are plenty of opportunities to trim waste in America’s $3.4 trillion health care system — but, as the Sutter example illustrates, it’s often not as simple as it seems.

At least $200 billion is wasted annually on excessive testing and treatment, according to an estimate by the Institute of Medicine, now called the National Academy of Medicine. This overly aggressive care also can harm patients, generating mistakes and injuries that are thought to cause 30,000 deaths each year.

“The changes that need to be made don’t appear unrealistic, yet they seem to take an awful lot of time,” said Dr. Jeff Rideout, chief executive of the Integrated Healthcare Association, an Oakland, California, nonprofit group that promotes quality improvement. “We’ve been patient for too long.”

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Progress may be slow — but there have been some encouraging signs. In San Diego, for instance, the Sharp Rees-Stealy Medical Group said it cut unnecessary lab tests by more than 10%.

A large public hospital, Los Angeles County-University of Southern California Medical Center, eliminated preoperative testing that was deemed superfluous before routine cataract surgery. As a result, patients got into surgery six months sooner, on average.

These efforts were sparked by the Choosing Wisely campaign, a national effort launched in 2012 by the American Board of Internal Medicine (ABIM) Foundation. The group asked medical societies to identify at least five common tests or procedures that often provide little benefit.

The campaign, also backed by Consumer Reports, encourages medical providers to hand out wallet-sized cards to patients with questions they should ask to ascertain whether they truly need a procedure.

Critics have knocked Choosing Wisely for playing it too safe and not going after some of the more lucrative procedures, such as certain spine operations and arthroscopic knee surgeries.

Daniel Wolfson, chief operating officer at the ABIM Foundation, said the Choosing Wisely campaign has been successful at starting a national conversation about unwarranted care. “I think we need massive change and that takes 15 years,” Wolfson said.

For patients, overtreatment can be more than a minor annoyance. Galen Gunther, a 59-year-old from Oakland, said that during treatment for colorectal cancer a decade ago, he was subjected needlessly to repeated blood draws, often because the doctors couldn’t get their hands on earlier results. Later, he said, he was overexposed to radiation, leaving him permanently scarred.

“Every doctor I saw wanted to run the same tests, over and over again,” Gunther said. “Nobody wanted to take responsibility for that.”

At Cedars-Sinai Medical Center in Los Angeles, officials said that economic incentives still drive hospitals to think more is better.

“We have excellent patient outcomes, but it’s at a very high cost,” said Dr. Harry Sax, executive vice chairman for surgery at Cedars-Sinai. “There is still a continued financial incentive to do that test, do that procedure and do something more.”

In addition to financial motives, Sax said, many physicians still practice defensive medicine out of fear of malpractice litigation. Also, some patients and their families expect antibiotics to be prescribed for a sore throat or a CT scan for a bump on the head.

To cut down on needless care, Cedars-Sinai arranged for doctors to be alerted electronically when they ordered tests or drugs that run contrary to 18 Choosing Wisely recommendations.

The hospital analyzed alerts from 26,424 patient encounters from 2013 to 2016. All of the guidelines were followed in 6% of those cases, or 1,591 encounters.

Cedars-Sinai studied the rate of complications, readmissions, length of stay and direct cost of care among the patients in whose cases the guidelines were followed, Sax said. It compared those outcomes with cases where adherence was less than 50%.

Related: Rural shoppers face slim choices, steep premiums on Obamacare exchanges

In the noncompliant group, patients had a 14% higher incidence of readmission and 29% higher risk of complications. Those complications and longer stays increased the cost of care by 7%, according to the hospital.

Cedars-Sinai said it avoided $6 million in medical spending in 2013, the first year of implementation of Choosing Wisely guidelines.

In Northern California, Sutter has incorporated more than 130 Choosing Wisely recommendations as part of a broader effort to reduce variation in care. In all, Sutter said it has saved about $66 million since 2011.

For her part, Giusto meets with Sutter doctors to present them with data on how many tests or prescriptions they order and how that compares to others. At one clinic, she shared slides showing that some doctors were ordering more than 70 opioid pills at a time when others prescribed fewer than 20. In response, Sutter set a goal of 28 tablets in hopes of reducing opioid abuse.

“Most of the physicians changed,” said Giusto, director of Sutter’s office of patient experience. “But there were still two who said, ‘Screw it. I’m going to keep doing it.'”

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

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Yearly Costs of Chronic Pain Exceed Those of Cancer, Heart Disease, and Diabetes

The annual cost of chronic pain is as high as $635 billion a year, which is more than the yearly costs for cancer, heart disease, and diabetes, say health economists from Johns Hopkins University in this month’s The Journal of Pain.

The researchers estimated the annual economic costs of chronic pain in the United States by assessing incremental costs of health care due to pain and the indirect costs of pain from lower productivity. They compared the costs of health care for people with chronic pain with those who do not report chronic pain. The authors defined people with pain as those who have pain that limits their ability to work, are diagnosed with joint pain or arthritis, or have a disability that limits capacity for work.

Data from the 2008 Medical Expenditure Panel Survey was used to gauge the economic burden of pain. The sample included 20,214 individuals 18 and older to represent 210.7 million US adults.

Results showed that mean health care expenditures for adults were $4,475. Prevalence estimates for pain conditions were 10% for moderate pain, 11% for severe pain, 33% for joint pain, 25% for arthritis, and 12% for functional disability. Persons with moderate pain had health care expenditures $4,516 higher than someone with no pain, and individuals with severe pain had costs $3,210 higher than those with moderate pain. Similar differences were found for other pain conditions: $4,048 higher for joint pain, $5,838 for arthritis, and $9,680 for functional disabilities.

Also, adults with pain reported missing more days from work than people without pain. Pain negatively impacted 3 components of productivity—work days missed, number of annual hours worked, and hourly wages.

Based on their analysis of the data, the authors determined that that the total cost for pain in the United States ranged from $560 to $635 billion. Total incremental costs of health care due to pain ranged from $261 to $300 billion, and the value of lost productivity ranged from $299 to $334 billion. Compared with other major disease conditions, the per-person cost of pain is lower but the total cost is higher.

The authors noted their conclusions are conservative because the analysis did not consider the costs of pain for institutionalized and noncivilian populations, for persons under 18, and for caregivers.

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Rep. Anna Eshoo, D-Palo Alto, has led a group of more than 70 Congressional members against President Donald Trump’s request to gather voter data from states for the Advisory Commission on Election Integrity, which held its first meeting Wednesday. The elected leaders signed an eight-page letter stating their concerns that releasing names, addresses, dates of birth and other highly sensitive information may put people at risk of identity theft and hacks. “The federal government has an obligation to protect the private information of Americans, but this request for personal voter data does the exact opposite,” Eshoo said in a press release.

TOP STORIESfrom the Palo Alto Weekly and the Palo Alto Online staff

Rape reported at Stanford student residence
The Stanford University Department of Public Safety is investigating an alleged rape that occurred a… (Thursday, 8:22 AM)

Maybell Avenue development moves ahead
A developer’s plan to build 16 homes on a former orchard site on Maybell Avenue scored a major victo… (Thursday, 9:53 AM)

Around Town: staged protest; downtown retail
In this week’s Around Town column, find out why the city has butt heads with the San Francisco Mime … (Thursday, 9:15 AM)

Pastor pleads not guilty to child molestation
A pastor from East Palo Alto pleaded not guilty Tuesday to allegations that he molested three minors… (Wednesday, 1:50 PM)

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HOT PICKSMust-see events recommended by our A&E editors


Concert: Jacknife: the Music of Jackie McLean
The Jazz Mentor Fellows are selected from nearly 200 applicants from all over the country to teach at the Workshop’s summer education programs. This year’s Mentor Fellows feature a swinging rhythm section and virtuosic horns. On the same evening, San Francisco saxophonist Steven Lugerner continues his explorations of the music of jazz legend Jackie McLean with Jacknife, a hard-hitting post-bop quintet, tonight, July 20, 7:30-9:30 p.m. at Dinkelspiel Auditorium, 471 Lagunita Drive, Stanford. Go to

Live Music: Music On the Plaza
Live music returns to downtown Palo Alto for six summer concerts at Lytton Plaza, tonight, July 20, 6-8 p.m. at Lytton Plaza, 202 University Ave., Palo Alto. Go to

Talk: Vinod Khosla: The Future of Technology
Vinod Khosla, entrepreneur, investor and founder of Khosla Ventures will discuss how to harness the entrepreneurial spirit to develop the clean technologies that are desperately needed, tonight, July 20, 7-8 p.m. at Oshman Family JCC, 3921 Fabian Way, Palo Alto. Go to


Concert: Jazz Camp Showcase 1
The free Stanford Jazz Camp Showcase features over 200 kids having the time of their lives, playing in bands and improvising, on four stages. In this action-packed community event, young musicians demonstrate the vocal and instrumental skills they’ve learned after spending a week immersed in Jazz Camp, tomorrow, July 21, 6-8 p.m. at Dinkelspiel Auditorium, 471 Lagunita Drive, Stanford. Go to

Family: Summer Outdoor Movie Night
The community is invited to celebrate how parks make life better with a movie under the stars. Tomorrow’s movie will be Disney’s “Moana” (PG 1 hour 53 min.). All movies begin at 8:30 p.m. or when dark outside. Guests should bring a blanket or lawn chair to sit on, tomorrow, July 21, 8:30-10 p.m. at Eagle Park, 652 Franklin St., Mountain View. Go

Family: Theatre in the Park
Peninsula Youth Theatre and the City of Mountain View present fairy tales and other children’s stories in a different 45-minute production each week performed by the children from Peninsula Youth Theatre’s “Theatre in the Park” summer camp program. Tomorrow’s show is “On the Tip of My Tongue,” a comic mystery adventure featuring characters from popular stories: Dorothy, Snow White and even Cruella Deville, tomorrow, July 21, 6:30-8 p.m. at ParkStage, 500 Castro St., Mountain View. Go to

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