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It's Time to B. Cereus: the Truth About Gut Microbiota and Childhood Obesity
Audrey Thomas
Kalamazoo College - Winter 2016

















In the past fifty years, Michigan's obesity rates have skyrocketed far beyond what anyone in the 1960s would have ever predicted. Obesity is defined as an excess of body fat that results from a skewed energy balance, so the person is in the 95 percentile of weight for their age; being overweight is when someone is in the 85-95 percentile range (Sanchez 2015). Overweight and obesity are troublesome issues in the average person's life - not only do these conditions affect adults, but they also target children at alarming rates. As of 2011, 13.2% of toddlers in Michigan were obese, whereas 14.8% of children aged 10-17 were (Michigan 2013). Obesity goes hand-in-hand with other co-morbitidies, such as Type 2 Diabetes, cardiovascular disease, and metabolic syndrome (Sanchez 2015). Studies have shown that children exposed to unhealthy food choices, lack of exercise, and live with other overweight or obese family members are more likely to obtain the condition themselves. Unfortunately, though, that does not account for the handfuls of children around the world who suffer from obesity yet do not meet any of the aforementioned criteria (Collen 2016). New York University Department of Medicine chairman and microbiologist Dr. Martin J. Blaser recently stated, "Bad eating habits are not sufficient to explain the worldwide explosion in obesity" (Specter 2012). Dr. Blaser is one of many prominent scientists in the world that believe that there is a missing component that is not focused on when it comes to tackling childhood obesity: gut microbiota, the bacteria in one's intestines and stomach. Recent studies have led to the conclusion that gut microbiota that deviate from the normal levels and types, in combination with the influences of specific lifestyle factors, contribute to the development of childhood obesity and overweight (Bervoets 2013). Due to this shift in thinking and the experimental results that have arisen, Michigan should begin to assess young children's gut microbiota, targeting that for treatment and prevention through physicians. Children in Michigan are becoming obese and overweight - in part - because of their lack of proper, healthy microbiota.












How do children lack healthy microbiota?

Children can acquire unhealthy gut microbiota in a plethora of ways. Two main focuses for childhood obesity researchers are the overuse of antibiotics, and the correlation between cesarean section births and obesity, as compared to vaginally-born babies. Both of these parallels are concerned with healthy microbiota, because either they kill or prevent healthy bacteria from colonizing the child. Without these bacteria, the child will be more likely to become obese or overweight due to the connections between harboring plentiful gut microbiota and weight.
	Cesarean sections are depleting natural microbial resources. Dr. Blaser has mentioned that "the way we live now, we are losing these organisms, and each generation arrives with fewer than the one before" (Specter 2012). In part, this is due to the growth in popularity of cesarean sections amongst expectant mothers across the globe, where 50% of Chinese women receive a cesarean section and more than a third of American women do. Cesarean sections are hindering the passing on of the mother's vaginal microbes to the baby; this is how mammals have been able to colonize their offspring with copious amounts of naturally healthy bacteria for the past 150 million years (Specter 2012). A seven year-long longitudinal study of over 28,000 Danish mothers found that children delivered via cesarean section were 10.9% and 8.3% more likely to be obese as they became seven year-old girls and boys, respectively (Ajslev 2011). Specifically, the researchers from this study also concluded that there was a tendency towards an increased risk of being obese in boys delivered by cesarean section (Ajslev 2011). In a separate study, 1255 children were followed from birth until age three, in attempt to see what percentage of children who were born via cesarean section became obese as a toddler. The results were shocking: out of the 284 children delivered by cesarean section, 15.7% were obese at age three compared to 7.5% of children born vaginally (Huh 2012). Just as Dr. Blaser had stated before, "We will need to make sure that pregnant women have the appropriate microbial communities to pass on to their children... That way, people can get the benefit of these organisms in early life without having to pay the cost as they age" (Specter 2012).
	In addition to cesarean sections reducing microbial diversity, the overuse of antibiotics in today's world can create a significant lack in a child's healthy gut microbiota. To Dr. Blaser, however, there should be an awakening about the risks of antibiotics: "Antibiotics are so miraculous that we have been lulled into a belief that there is no downside. But there is: they kill good bacteria along with the bad bacteria" (Specter 2012). In the majority of American children's lives, there will be courses upon courses of antibacterial drugs given to them - for some, that is roughly one round of antibiotics every other year. By the age of eighteen, the average American child will receive between ten to twenty courses of antibiotics. Over 43 million doses of antibiotics were dispensed in 2010 (Specter 2012). This means that millions of people are diminishing themselves of healthy gut microbes alongside the ones causing infection. A 2013 research study found that both oral and intravenous antibiotics decreased the bacterial load within the digestive tract. Metronidazole, cefoperazone, and vancomycin led to significant decreases in overall bacterial biomass in the intestines; these drugs targeted Lactobacillus, a very important bacteria involved in maintaining digestive health. Researchers from this group also pin-pointed that clarithromycin, an antibacterial drug used to target stomach-ulcer-causing Helicobacter pylori was associated with weight gain and acquired obesity. Other sulphonamide antibacterial medications have been linked to weight gain, as well (Million 2013). Moreover, Dr. Blaser's research team at New York University found that once they fed antibiotics to mice that were comparable to those used to treat children with ear infections, the mice who were given the drugs gained considerable weight, while the control group did not - despite eating the same, unchanged diet (Specter 2012). Alongside these alarming lab results from all studies is the reality behind antibiotics: many physicians are over-prescribing antibiotics to children for viral infections, upon which they do not work. They do this as a safety precaution, "just in case" the ear infection happens to be bacterial, rather than viral - even though viral infections cause 90% of upper respiratory infections (Resistance 2014). Over-prescribing antibiotics is one of the issues standing in the way of children having healthy gut microbiota.
	All in all, there is substantial evidence accusing both antibiotics and cesarean sections of harming children in the long-run by reducing their gut microbiota in both volume and diversity. Cesarean sections reduce microbial colonization during the birthing process, which is the first initial contact the newborn has with bacteria - and the one moment in the child's life that instantly predicts what their gut microbiota will be like. Antibiotics reduce microbial diversity through their species-specific targeting, killing off both the "good" and the "bad" bacteria in one's intestines. Whenever a child is born via a cesarean section, or given a dosage of antibiotics to curb a urinary tract or ear infection, part of his or her gut microbiota - or prospective microbiota - dies off. Lacking these helpful bacteria may be the key as to why children today, in Michigan and across the world, are gaining weight.











What proof is there correlating gut microbes and childhood obesity?

There are universal studies done that have bridged the gap between a low intestinal bacterial diversity and obesity. By studying obese versus lean children's fecal matter, researchers have been able to test which microbes are missing in obese children's digestive tracts, as well as which microbes may protect against the unhealthy life conditions. Microbes flourish in specific conditions that suite them the best. A child eating a low fat, high fiber diet would have very few microbes specialized to breakdown and deal with fatty foods, such as a doughnut or a piece of candy. A child eating a high fat, high sugar diet would have a large amount of microbes specialized to breakdown and work with fatty foods (Collen 2016). Large-scale alterations of a child's gut microbiota could impact his or her metabolism through signaling pathways in the gut, with lasting effects on inflammation, insulin resistance, and deposition of energy in fat stores (Ley 2010). Restoration of the child's intestinal bacteria to a much healthier state may alleviate conditions associated with overweight or obesity and help him or her maintain a healthy weight (Ley 2010). With this idea in mind, one could hypothesize that not having a diverse group of intestinal bacteria would catalyze overweight or obesity in a child.
	There are multiple, credible studies that have been conducted to help create a connection between obesity and the low amounts of diverse of gut microbiota in children. Recent microbiology research has shown that there is a large shift in the representation of different dominant phyla of bacteria in obese children's intestines when compared to lean children's (Ley 2010). In one cross-sectional study, 26 overweight and obese (mean BMI: 28.7 ± 6.5) and 27 lean (mean BMI: 16.5 ± 2.1) children aged 6 to 16 gave researchers fecal samples to detect what types of bacterial species inhabited their intestines. Obese children had a higher Firmicutes levels, which is a species of bacteria that are specialized to digest fats; they also had a much lower Bacteriodetes level, which is a species of bacteria specialized in digesting carbohydrates. The researchers mentioned that their findings corroborate that there is a significant difference in the gut microbiota composition between obese and lean children (Bervoets 2013). Adding on to that study is another that compared the fecal matter of 25 overweight or obese and 24 normal-weight children. Researchers found that children of a normal weight showed higher Bifidobacterium levels in their intestines than obese children, a Bacteriodete (Kalliomäki 2008). Other studies also found similar results. One study done on preschoolers' gut microbiota illuminated the spike of Enterobacteriaceae in obese children's fecal matter; this was coupled with a sharp drop in their levels of A. miciniphila-like bacteria, as well as healthy Desulfovibrio. Both latter bacteria are associated with healthy digestion in lean individuals (Bervoets 2013). From these conclusions, one can see that there is a highly specific trend for decreased bacterial diversity in children with excessive body weight (Karlsson 2012).
	Additionally, researchers have found a compelling parallel between cesarean section births and obesity in children. After studying 25 overweight or obese and 24 lean children, researchers found a larger number of Staphylococcus aureus in obese children [0.64 × 106 cells/g ± (0.33–1.00× 106 cells/g)] than in normal-weight children [0.27 × 106 cells/g  ± (0.17–0.50 × 106 cells/g); P = 0.013] (Kalliomäki 2008). In fact, the colonization of Staphylococcus aureus in obese children has been linked to cesarean sections. When removed from the uterus, rather than being colonized by the mother's healthy vaginal bacteria, the infant is colonized by bacteria lingering in the air, which is most likely to be the most abundant bacteria in the hospital - Staphylococcus aureus (Blaser 2014). In short, this study assisted in connecting cesarean sections to obesity.
	Moreover, there is significant data that correlates a stomach bacterium with two hormones that control and maintain the regulation of appetites - a topic especially pertinent to childhood obesity and overeating. Dr. Blaser and his colleagues at New York University found a strong relationship between the bacterium Helicobacter pylori and the hormones ghrelin and leptin, which both deal with appetite regulation. Working as a team, ghrelin and leptin inform a child to eat when he or she is hungry, and to stop eating when he or she is full. Ghrelin is associated with overeating; if there is more ghrelin in a child's bloodstream, he or she is likely to overeat. Leptin functions oppositely by suppressing the child's appetite and increasing his or her energy levels (Specter 2012). Helicobacter pylori comes into play, because children who have been colonized by the bacterium have ghrelin levels that are less detectable after a meal. Children without Helicobacter pylori in their system have high levels of ghrelin after eating a meal; these children tend to overeat (Blaser 2014). Without ghrelin being identifiable, the message given to children to stop eating never makes it to the brain. If the hormones are not in-check and out-of-control, it would make it extremely difficult to control one's weight (Specter 2012). Dr. Blaser later stated that children are not being colonized with Helicobacter pylori because of the overuse of antibiotics and mothers not passing the bacterium to their children via vaginal births. All in all, there is a strong correlation between a child's lack of Helicobacter pylori in his or her stomach and the secure chance of becoming obese or overweight as a result of the bacterium not being present to regulate hormones and appetite (Blaser 2014).
	There is undeniable proof that has bridged the gap between a child's missing gut microbiota and his or her chance of becoming overweight or obese. Dependable studies have shown again and again that obese children lack the amount of healthy, carbohydrate-digesting Bacteriodetes bacteria; instead, their gut microbiota are primarily Firmicutes bacteria, specialized to digest fats. One study concluded that there are higher amounts of Staphylococcus aureus in the gut microbiota of obese children and those who have been born via cesarean sections. In addition, there is a parallel between children lacking Helicobacter pylori in their stomachs and regulating the hormone ghrelin, which increases appetite. Without this bacteria, children constantly feel hungry - this may be a missing link between gut microbiota and obesity. Evidence showing that the lack of microbial diversity in a child's digestive tract leads to obesity is irrefutable.
































What should Michigan do about gut microbiota and childhood obesity?

Obesity is a rising pandemic, swallowing the United States whole. Scientists hypothesize that by 2030, 86% of the American population will be overweight or obese; by 2048, everyone will be (Collen 2016). Michigan is no exception. For the past fifty years, Western countries have believed that the fundamental cause of obesity and overweight, especially that in children, is caused by an energy imbalance between calories consumed and calories expended. But this does not explain why children who have healthy parents, eat organic foods, and exercise daily are winding up obese later in life. In the past ten years, the accepted reality about calorie-overloads and obesity has shifted drastically (Collen 2016). Luckily, thanks to credible, scientific studies, researchers have found strong correlations between obesity and low microbial diversity in the digestive tracts of children- the one piece of the puzzle that could help those who are overweight or obese and do not fit the mould of an stereotypically "unhealthy" person. Missing microbiota in children's stomachs can explain the sharp increase of obesity in the past half-century.
	There are quite a few steps that Michigan, its physicians, and its citizens can do to prevent more children from becoming overweight and obese in the future. To start, families should be given adequate information about how plentiful, diverse gut microbiota helps sustain a healthy life. Physicians should warn parents-to-be about the risks associated with elective cesarean sections - particularly informing them about the correlation between cesarean births and obesity in children. In addition, physicians should hold-back on prescribing antibiotics to young children and babies, due to their effective eradication of healthy gut microbiota. Physicians should also begin studying each child's stool when they visit for a routine check-up, to ensure that their internal bacterial levels are at a healthy level. Lastly, researchers and physicians should study the possible benefits of prebiotics and probiotics for children who are lacking important gut microbiota, intervening in obesity's path early-on.
	Primarily, Michigan physicians, including OBGYNs, should sit down with parents-to-be and have discussions about the risks affiliated with elective cesarean sections, and how they are likely to contribute to their future child's weight. There is substantial evidence to show that children colonized with non-maternal bacteria while in the hospital are more likely to become obese in the long-run. Parents should know the risks and make their birthing decision based on their child's health, rather than the mother's potential pain level or ease of recovery. Through these discussions, physicians and parents could prevent future children from lacking the gut microbiome that they would so desperately need to combat obesity later in life.
	In addition to the new active-discussion approach to medicine, physicians should more regularly test infections to be absolutely certain that it is bacterial before administering an antibiotic to a child. Many physicians across the country prescribe antibiotics to patients who have viral infections - only to ease the patient's anxiety about being ill. This action actually depletes the child's gut microbiome as the antibiotic runs its course, killing specified targets. The excuse for administering antimicrobial drugs - even though 90% of upper-respiratory tract infections are caused by viruses - is that doctors want to "be safe", and give the child the prescription "just in case" the infection is not a virus (Resistance 2014). However, in the end, there is more harm done when a child is given antibiotics. Rather than handing children and their parents cocktails of drugs for an infection that could not even be bacterial-in-nature, physicians should have mandatory tests and steps they must go through before implementing a course of medicine. By checking that every single infection is positively bacterial, physicians prevent the possible loss of diversity in the gut microbiota of children, which can prevent on-set obesity, since children with less microbial diversity are more likely to become overweight or obese.
	Ultimately, researchers and physicians around the world should continue studying prebiotics and probiotics, as well as which best prevents obesity in children. Currently, no prebiotics nor probiotics have been approved by the Federal Drug Administration to be classified as a drug, so they are considered to be dietary supplements (Specter 2012). One source of hope for children suffering from overweight or obesity are prebiotics. Prebiotics are defined as food ingredients that stimulate the growth of a limited bacteria in gut microbiota; prebiotics have been hypothesized increase the microbial diversity in the gut (Million 2013). In one study, the administration of the prebiotic oligofructose of high-fat-fed mice increased their abundance of Bifidobacterium, Lactobacillus, and C. coccoides, and normalized their inflammatory bowel responses to their diet (Million 2013). Additionally, another source of hope for overweight or obese children are probiotics. They are the far more popular option for dietary relief when compared to prebiotics, having quadrupled sales between the years of 1998 and 2012 (Specter 2012). Probiotics are defined as live bacteria that are thought to be beneficial to one's digestive tract (Million 2013). In one specific study, 87 overweight adults were given fermented milk containing the bacterium Lactobacillus gasseri SBT2055, and were told to drink 200 grams of it daily for twelve weeks, as well as maintain a low-calorie diet. Some participants opted to consume two yogurts per day that were supplemented with Lactobacillus amylovirus. By the end of the twelve weeks, all participants reduced their visceral and subcutaneous fat levels, their body weight, and their BMI compared to a control group that just stuck to a low-calorie diet and regular yogurt and milk (Sanchez 2015). Other studies with similar methods had very similar results. Providing overweight and obese adults with Lactobacillus plantarum and Lactobacillus gasseri strains had an anti-obesity effect, reducing their abdominal fat reserves, body weight, and BMI (Million 2013). But these effects were not solely observed in adults. In a study of 70 overweight and obese children, after given a strict eight-week regimen of oligofructose prebiotics, Lactobacillus rhamnosus probiotics, and vitamins A, C, and E, they significantly reduced their BMI, waist circumference, waist/hip ratio, body fat levels, and low-density lipoprotein (LDL) cholesterol as compared to children given placebos (Sanchez 2015). With all the studies surrounding prebiotics and probiotics, there are still no definitive answers when it comes to which types and combinations aid children in preventing and battling obesity. Hopefully, this will become the missing link needed that, in association with healthy eating and exercise, abolishing obesity in children.
	In the end, Katherine Lemon, a microbiologist and professor of pediatrics at Harvard Medical School said it best: "I can envision a conversation with the parents where the pediatricians would say, 'Your child's blood work is fine. She is hitting all her milestones and she looks great. But after seeing her gut microbiome, given the history of inflammatory-bowel disease in your family, I would like to prescribe a probiotic that can help populate her intestines with the proper combination of microbes'" (Specter 2012). Lemon envisions the future of pediatrics, the future of healthcare. A future where children have mandatory stool samples taken at each periodic check-up with their pediatrician or family physician, to ensure that their gut microbiome is as healthy as it should be. This is particularly important when it comes to preventing overweight and obesity in children in the State of Michigan, in the United States, and in the world. If a child has an unhealthy gut microbiota, his or her physician would be able to prescribe a helpful probiotic to boost them back to the standard of health, as Lemon stated. Physicians would inform parents-to-be about the dangers of cesarean sections harming their unborn child's future gut microbiome. They would have required tests to undergo before prescribing unnecessary antibiotics to any child, regardless of whether or not any doctor believes administering drugs "just in case" is fine. With all these precautions in-line, children everywhere will be able to live happy, healthy, obesity-free lives. A lean body really does start from the inside-out.














Figure 1. Pathways in microbe-induced obesity (Cox, 2013).


























Works Cited

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