More on Childhood Obesity and Antibiotics

This post continues an overview of some investigations into the suspected connection between antibiotics and obesity. In 2016 a ScienceDaily.com piece said,

In the last five years, scientists have made compelling discoveries showing that there may be a connection between the amount and type of bacteria in the intestines and weight gain.

The theory is that antibiotics knock out beneficial bacteria and clear space for harmful ones, although another school of thought proposes that what matters may not be the types of bugs, so much as the balance of power maintained between them.

At any rate, when antibiotics flood the system, massive numbers of our microbial tenants are slaughtered and the result is dysbiosis. It appears that the disturbance “may increase calorie absorption, slow metabolism and cause very low levels of inflammation — all of which appear to trigger a chain reaction that alters the behavior of fat cells.”

PCORnet

The PCORnet Obesity Observational Study is both meta and longitudinal, prenatal and post-birth. It investigates such questions as the effect on the fetus if the mother is prescribed antibiotics while pregnant. If a baby escapes that hazard before being born, the researchers are intensely interested in the first administration of antibiotics to the baby itself, and what happens as a consequence.

The task of PCORnet is to examine the medical records of 42 healthcare systems and figure out what is going on with more than a million and a half children. The activities are coordinated by the Duke Clinical & Translational Science Institute and Harvard Pilgrim Health Care Institute.

One part of the project, in which multiple researchers analyzed data from 35 institutions, concerning more that 362,000 children, concluded:

Antibiotic use at <24 months of age was associated with a slightly higher body weight at 5 years of age.

An article published by Frontiers in Pharmacology explains the alarming maps that illustrated yesterday’s post. Data collected in 2014 revealed that for every 1,000 Americans, 835 antibiotic prescriptions were written and filled. When separated by state, and graphically illustrated, the result is a stark admission of undeniable alignment, “a positive and strong correlation, meaning that the higher the use of antibiotics the higher the rate of obesity at that place.”

The authors write,

The scientific community has reached a consensus on the relationship between antibiotics and obesity, showing beyond any doubt that the use of antibiotics causes dysbiosis to varying degrees, especially in children (with less than 3 years of age), which can trigger an increased energy intake from the diet with concomitant increase of weight.

Two more brief notes of confirmation: Clinical Pharmacist published a study of almost 300,000 children who had been given both antibiotics and acid suppressants in the first two years of life. It used data on “241,502 children prescribed an antibiotic, 39,488 children prescribed an H2 receptor antagonist (H2RA) and 11,089 children prescribed a proton pump inhibitor (PPI)” and concluded that…

[…] antibiotic exposure was associated with a 26% increased risk of obesity… Combinations of exposure to the three medicine types were associated with increasing risk of obesity, with those exposed to all three having a 42% increased risk.

A recent report from the United Kingdom adds to the sum of knowledge:

Children who receive four or more courses of antibiotics between the ages of two and three years are more likely to be obese by the age of five, a study by Trinity College Dublin has found. The study […] found no statistical increase in weight for children who received fewer than four courses of antibiotics.

One of the implications affecting not only children but adults is that the composition of the microbiome might explain why obesity is such a difficult process to reverse. No matter what a person does or neglects to do regarding weight loss, failure might be inevitable if the obesity is caused by the same cast of characters continuing to reside in the digestive system.

Your responses and feedback are welcome!

Source: “Swelling obesity rates may be tied to childhood antibiotic use,” ScienceDaily.com, 08/30/16
Source: “Early Antibiotic Exposure and Weight Outcomes in Young Children,” AAPPublications.org, December 2018
Source: “Obesity: A New Adverse Effect of Antibiotics?” FrontiersIn.org, 12/03/18
Source: “Early life exposure to antibiotics and acid suppressants increases obesity risk,” Pharmaceutical-Journal.com, 12/18/18
Source: “Childhood obesity linked to courses of antibiotics,” TheTimes.co.uk, 01/20/19
Photo credit: kleuske on Visualhunt/CC BY-SA

Childhood Obesity and Antibiotics, Continued

Once the idea had been floated that antibiotics might have something to do with obesity, academics started looking into it. They faced the challenge of corralling vastly dissimilar data sets into coherence and usable order.

Always, parameters need to be drawn, and boundaries observed. A team might start out with what looks like a lavishly sufficient number of subjects, but then reject half of them because their 5-year-old weights had been recorded by parents rather than professionals. Often, scientists begin with bright hopes, but have to abandon a hypothesis because there is simply not enough of the right kind of information to do anything with.

In 2012, news appeared of a longitudinal birth cohort study designed to “examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life.” They had the records of more than 11,000 children to work with, and landed squarely on intestinal colonization, or rather the interference with it by the administration of antibiotics, or by bottle feeding. Their report said,

Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6–14 months, 15–23 months) are not consistently associated with increased body mass.

A 2014 study added to the knowledge:

Using electronic health record data from 64,000 children, our research team identified an exposure-response association between the number of antibiotic treatment episodes during the first 2 years of life and development of obesity in later childhood, an effect that was most pronounced for broad-spectrum antibiotics.

That is another obstacle to designing good studies. There might be several thousand more potential subjects of the right age and other qualifications, but they took a different type or class of antibiotic. That would make an interesting study too, but it might not be the one on the table at the moment.

The United Kingdom’s National Health Service generates an awesome amount of data. A 2016 research team was concerned that antibiotics had been used for decades to promote weight gain in animals sold for human consumption. They set up a retrospective cohort study of the records of more than 20,000 children, aka “a population-representative dataset of >10 million individuals” and concluded,

Administration of 3 or more courses of antibiotics before children reach an age of 2 years is associated with an increased risk of early childhood obesity.

In the illustration at the top of the page, the map on the left represents obesity rates, while the map on the right represents antibiotic prescriptions. They come from the Centers for Disease Control by way of Frontiers in Pharmacology.

Your responses and feedback are welcome!

Source: “Infant antibiotic exposures and early-life body mass,” Nature.com, 08/21/12
Source: “Antibiotics, infections, and childhood obesity,” NIH.com, 11/01/16
Source: “Administration of Antibiotics to Children Before Age 2 Years Increases Risk for Childhood Obesity,” GastroJournal.org, July 2016
Image by Centers for Disease Control

Childhood Obesity and Antibiotics

Much has been written about the relationship between antibiotics and obesity, a subject that is not likely to be exhausted any time soon. Generalizations are difficult because of, once again, multifactorialism. For instance, there are different kinds of antibiotics.

Researchers cannot keep a gang of human subjects under strict control and dose them with different amounts of antibiotics to see what happens; or round up people with infections and divide them into a group that receives antibiotics and another group that doesn’t. That would be profoundly unethical and illegal. They have to depend on records created for other purposes. Those records may not accurate (if, for instance, the patient does not finish all the pills) and are usually not kept with the intention of tracking weight.

Many medical professionals now believe that antibiotics are grossly overprescribed. In addition, the rampant overuse is evident in animal products, which people eat. This is particularly concerning because about 75 percent of the antibiotics fed to animals are not absorbed. According to one estimate, around 22 million pounds of antibiotics are excreted, each year, into wherever factory-farmed animals’ urine and feces end up. Just call it the environment.

An early start

Exposure to antibiotics is common, even before birth. In nations that practice Western medicine, about 80 percent of the drugs prescribed to pregnant women are antibiotics, and about one-third of pregnant women are prescribed at least one systemic antibiotic treatment. Nobody knows how the in utero fetus is affected. Vaginal birth baptizes a baby with microbes on the way out, an experience of which a C-section baby is deprived. Opinion is solidifying into certainty that the omission can have serious consequences.

Because of neonatal sepsis, some newborn babies are treated with IV antibiotics, and there are other reasons for administering them during the first six months. Most probably, antibiotics cause obesity by slaughtering the gut flora. One doctor compared a round of antibiotics to a forest fire. The good bugs die along with the bad bugs, and a healthy population might not be restored for a couple of years, if ever. Many in the medical field now believe that the baby’s microbiome needs to be stocked up with organisms from the mother, to jump-start the establishment of the microbial colonies that will have such a pervasive influence throughout life.

How long has this been going on?

Way back in 1955, the U.S. Navy experimented on a bunch of recruits, and learned that “a 7 week course of antibiotics led to significantly greater weight gain in the treated group compared with placebo.” In 2009, New York University researchers fed low doses of penicillin to lab rodents for 30 weeks, with the result that “penicillin-fed mice were between 10 and 15 per cent bigger and twice as fat as drug-free mice.”

In 2011, Danish scientists hypothesized that “environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight.” They reported,

This effect may potentially be explained by an impact on establishment and diversity of the microbiota… Exposure to antibiotics in infancy was found to increase the risk of childhood overweight in offspring of normal-weight mothers, while to some extent reducing the risk of overweight in children of overweight or obese mothers.

(To be continued…)

Your responses and feedback are welcome!

Source: “Antibiotics, infections, and childhood obesity,” NIH.gov, 11/01/16
Source: “Surprise: Antibiotics May Be Contributing to the Obesity Epidemic,” ANH-USA.org, 04/03/12
Source: “Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics,” Nature.com, 03/08/11
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Multietiological Stew

Recently, the journal Childhood Obesity published a piece titled “Behavioral Research Agenda in a Multietiological Approach to Child Obesity Prevention” that emphasizes once again, in case we ever forget for a minute, how complicated life can be.

Etiology is a branch of medical knowledge concerned with the root causes of illness, which first proved its usefulness by saving the lives of people who would otherwise have been condemned as witches. With the realization that diseases come from germs, not curses, the human race hit a huge turning point.

For centuries, we could only play catch-up, scrambling to alleviate symptoms as effectively as possible, occasionally managing to keep some sick people alive, and maybe even seeing some of them recover. Eventually, it got to where we could look a little deeper and figure out how to prevent suffering.

Of course, it was never easy. Tradition is always a formidable barrier. It took quite a few years for surgeons to accept that hand-washing prevents the spread of disease. It seems that in each new iteration of the discovery journey a mountain of resistance has to be overcome.

Now what?

The human tendency to cling to old ways is especially prevalent when we are stuck in the middle, acknowledging that the old way doesn’t work, yet unable to see a clear path forward. “So, Answer A doesn’t work. Fine. What does work? Now you’re telling me, it might be Answer B, or C, or D…” Even people who are willing to try something different are tempted give up in despair.

But when multifactorialism shows up, it gets even worse. “Oh great, now you say it could be a combination of things? A little bit of A, plus a dollop of B, and a heaping helping of C, and just a dash of D…” Factors work together in uncharted ways, and synergy can throw a monkey wrench into any theory.

Multietiological approach

This paper has three authors, Tom Baranowski, Ph.D.; Kathleen J. Motil, M.D.; and Jennette P. Moreno, Ph.D. It begins with the stark admission,

Serious limitations have been found in the simple energy balance model (energy in — energy out) as the single or primary biological strategy for virtually all child obesity prevention interventions. Experts have criticized it for not reflecting the likely multifactorial nature of obesity.

Right up there in the first paragraph, the authors note that “A substantial number of other possible, even likely, causes of obesity have been identified.” This paper discusses three of those potential causative (or at least complicating) factors — infectobesity, the microbiome, and biorhythms.

At present, infectobesity refers mainly to the activities of adenovirus 36, although other, as yet unsuspected organisms might do similar damage. Regarding adenovirus 36, we need to know how the infection gets a foothold and how it spreads, and why; and whether the possibility exists of a vaccine to prevent it:

If we assume that not everyone who is infected becomes obese, it would be important to know the behaviors and other exposures that minimize or enhance viral infection immunity in general and resistance to adenovirus 36 in particular.

The introductory sentences of the microbiome section hint at the complexity:

Imbalances in the bacterial (and maybe the viral, fungal, and eukaryotic) phyla in the microbiome can lead to obesity. The microbiome begins to develop (from the mother) in the immediate postnatal period and changes substantially early in life, due, in part, to diet and physical activity influences.

That’s a lot of ifs and maybes, packed into one short paragraph. Then, with the addition of circadian and circannual rhythms, things really get crazy:

Once the operative nutritional factors can be identified, the role of school and family influences on chronobiology, meal content, and timing may be determined. Longitudinal analyses of interrelationships among diet, physical activity (PA), sedentary behaviors, sleep, and indicators of circadian rhythmicity are needed, including their impact on the microbiome.

As always — and this will not come as a surprise — the need for additional research, both wide and deep, is emphasized. Childhood obesity is not an easy nut to crack.

Your responses and feedback are welcome!

ANNOUNCEMENT

If you have a child between the ages of 14 and 18 years that is overweight and can read English, you may be eligible for a clinical research study at the Children’s Hospital of Los Angeles (CHLA) that is currently recruiting participants. Please visit http://bit.ly/CHLA-Study for more information.

Source: “Behavioral Research Agenda in a Multietiological Approach to Child Obesity,” PreventionLiebertPub.com, 04/22/19
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