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What things in our environment have an effect on the microbes living within us? We now know that gut microbes are important for our health in many ways, and that thousands of species of bacteria, as well as viruses, fungi, and other microbes normally live in a healthy person's gut. We refer to these microbes as the human microbiota or human microbiome. When the community of gut microbes is thrown out of whack (dysbiosis) there can be a number of negative health effects, including diseases. Researchers are just learning about all the microbes within us and their importance in health and disease. [See all posts on the human microbiome.]

Past posts have discussed such things as antibiotics, emulsifiers, different foods and diets, heartburn drugs, etc. having an effect on the human microbiome, but what else? A recent study from China reviewed some environmental pollutants and their effects on gut microbiota - as shown in both human and animal studies. They reviewed studies on antibiotics, heavy metals (arsenic, cadmium, lead), persistant organic pollutants or POPs (organochlorine pesticides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers, and polycyclic aromatic hydrocarbons or PAHs), pesticides (permethrin, chlorpyrifos, pentachlorophenol, epoxiconazole and carbendazim, imazalil), emulsifiers, nanoparticles (e.g., silver nanoparticles), and artificial sweeteners. They found that all these environmental pollutants had effects on gut microbes - with some effects lasting for years. Their conclusion: gut microbes are very sensitive to drugs, diet, and environmental pollutants. By the way, notice that popular food ingredients such as emulsifiers and artificial sweeteners were considered "environmental pollutants" by the researchers.

Excerpts from Environmental Pollution: Effects of environmental pollutants on gut microbiota

Environmental pollutants have become an increasingly common health hazard in the last several decades. Recently, a number of studies have demonstrated the profound relationship between gut microbiota and our health. Gut microbiota are very sensitive to drugs, diet, and even environmental pollutants. In this review, we discuss the possible effects of environmental pollutants including antibiotics, heavy metals, persistent organic pollutants, pesticides, nanomaterials, and food additives on gut microbiota and their subsequent effects on health. We emphasize that gut microbiota are also essential for the toxicity evaluation of environmental pollution. In the future, more studies should focus on the relationship between environmental pollution, gut microbiota, and human health.

Thousands of species are found in the gut microbiome, and the majority of these species belong to six bacterial phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia (Eckburg et al., 2005). Gut microbiota are highly dynamic and have substantial interindividual and intraindividual variation....The gut microbiota are very essential for host health. They participate in the regulation of many physiological functions. The gut microbiota reside in our intestinal mucus layer and even participate in shaping the mucus layer (Jakobsson et al., 2015). They help us to digest food (such as fiber); synthesize vitamins and amino acids (Spanogiannopoulos et al., 2016); play very important roles in energy metabolism and storage, immune system modulation, growth, and neurodevelopment; and can even regulate our behavior.... The occurrence of many diseases is correlated with altered gut microbiome composition (Lange et al., 2016). Gut microbiota dysbiosis is considered to be a potential cause of obesity (Cani et al., 2007; Fei and Zhao, 2013). However, gut microbiota are very sensitive to drugs, diet, and environmental pollutants.

Although most environmental pollutants do not directly target gut microbiota, some pollutants can enter the body and interact with the gut microbiota through different pathways. A number of previous studies have shown that exposure to environmental pollutants can alter the composition of the gut microbiome, leading to disorders of energy metabolism, nutrient absorption, and immune system function or the production of other toxic symptoms (Jin et al., 2015c; Zhang et al., 2015b). In the present review, we conclude that different kinds of environmental pollutants can induce gut microbiota dysbiosis and have multiple potential adverse effects on animal health

Heavy metals in the environment have become a severe health risk in recent years (Liu et al., 2016a). As a common form of environmental pollution, heavy metals are associated with a wide range of toxic effects, including carcinogenesis, oxidative stress, and DNA damage, and effects on the immune system..... Recently, several studies have stated that heavy metal exposure could also lead to gut microbiota dysbiosis, indicating that study of gut microbiota provides a new approach to analyze the mechanisms of heavy metal toxicity

Immune system function is tightly coupled to our gut microbiome. Gut microbiota and their metabolites can interact with both the innate immune system and the adaptive immune system (Honda and Littman, 2016; Thaiss et al., 2016).... Alterations in the gut microbiome can disrupt the balance between the host immune system and gut microbiota, induce immune responses, and even trigger some immunological diseases. Furthermore, immune system imbalance may influence the microbiota metabolites. For example, trimethylamine, which is absorbed from food by gut microbiota, can induce atherosclerosis (Chistiakov et al., 2015).

For years it has been known that most children with autism spectrum disorder (ASD) have all sorts of gastrointestinal (GI) problems (e.g., constipation, diarrhea, stomach pain, food intolerance), and the more severe the autism, the more severe the GI problems. Recent studies suggested that a major factor in this are abnormal gut bacteria, with the gut microbial community out of whack (dysbiosis). Previous studies looking at the gut microbiome of children with autism have shown lower diversity and lower amounts (abundances) of certain bacteria in children with autism compared to neurologically normal (neurotypical) children.

A recent study of children with autism spectrum disorder found that giving the children a fecal microbiota transplant (FMT) led to significant and lasting improvements in both gastrointestinal (GI) symptoms and autism-related behaviors and symptoms. A fecal microbiota transplant (FMT) is a transplant of fecal matter from a healthy donor to the recipient. A fecal microbial transplant contains approximately a thousand bacterial species that live in a healthy gut, as well as other microbes such as viruses and fungi. FMTs have so far been an amazingly successful treatment for recurrent Clostridium difficile infections, and are now being looked at as promising treatments of chronic inflammatory diseases such as inflammatory bowel disease.

The researchers were surprised to see an 80% improvement in gastrointestinal symptoms, especially abdominal pain, indigestion, diarrhea, and constipation. They also saw about a 25% improvement in autism related behaviors and symptoms which persisted for 8 weeks after treatment stopped, which is when the study ended. One measurement of adaptive behaviors (such as communication, daily living skills, and socialization) found that the average developmental age increased by 1.4 years after treatment. The researchers also found that there was a "rebalancing" of the gut microbes following treatment. They found evidence of "successful partial engraftment of donor microbiota and beneficial changes in the gut environment" - meaning they could see that donor microbes were living in the gut. Also, overall bacterial diversity increased (which is good) and the abundance of certain bacteria increased (including Bifidobacterium, Prevotella, and Desulfovibrio), and these changes persisted until the end of the study.

The researchers caution that this was a small trial, that there could be placebo effects, and so the results should be "cautiously interpreted and viewed as preliminary." But nonetheless, the results are exciting. Really exciting. From Science Daily:

Autism symptoms improve after fecal transplant, small study finds

Children with autism may benefit from fecal transplants -- a method of introducing donated healthy microbes into people with gastrointestinal disease to rebalance the gut, a new study has found. Behavioral symptoms of autism and gastrointestinal distress often go hand-in-hand, and both improved when a small group of children with the disorder underwent fecal transplant and subsequent treatment. In the study of 18 children with autism and moderate to severe gastrointestinal problems, parents and doctors said they saw positive changes that lasted at least eight weeks after the treatment. Children without autism were included for comparison of bacterial and viral gut composition prior to the study.

Previous research has established that children with autism typically have fewer types of some important bacteria in their guts and less bacterial diversity overall -- a difference that held true in this study. That could be because many of them are prescribed a lot of antibiotics in the first three years of life, the research team wrote in the study.

Parents of the children not only reported a decrease in gut woes including diarrhea and stomach pain in the eight weeks following the end of treatment: They also said they saw significant changes for the better when it came to behavioral autism symptoms in their sons and daughters, who ranged from 7 to 16 years old....One of those tools showed the average developmental age increased by 1.4 years after treatment. 

Researchers also were able to document a rebalancing of the gut following treatment. At the end of the study, the bacterial diversity in the children with autism was indistinguishable from their healthy peers. The study also included a unique viral analysis by Ohio State scientists, made possible because of previous work in the world's oceans. Gregory, who is particularly interested in the interplay between viruses and bacteria, used genetic testing to examine the viral diversity in the guts of the treated children. It rebounded quickly, and became more similar to the donor's microbiome. "Those donor viruses seemed to help," she said.

Fecal transplantation is done by processing donor feces and screening it for disease-causing viruses and bacteria before introducing it into another person's gastrointestinal tract. In this study, the researchers used a method called microbiota transfer therapy, which started with the children receiving a two-week course of antibiotics to wipe out much of their existing gut flora. Then, doctors gave them an initial high-dose fecal transplant in liquid form. In the seven to eight weeks that followed, the children drank smoothies blended with a lower-dose powder[Original study.]

Flame retardants are in many products around us, both in and out of the home, but there is much concern over their health effects on humans. Older flame retardants (PBDEs) were phased out by 2013, but it turns out that the newer replacements (TBB and TBPH, including Firemaster 550) also get into people and also have negative health effects. So it shouldn't be a surprise that every single toddler tested in a study in New York City showed evidence of flame retardants on their hands (both the old kind and newer replacements), and that they had more on their hands than their mothers. Flame retardants were also found in all house dust samples. Since they are linked to many negative health effects, you really, really want to minimize the amounts in your body.

More and more research is finding health problems with flame retardants because they are "not chemically bound" to the products in which they are used - thus they escape over time. and get into us via the skin (dermal), inhalation (from dust), and ingestion (from certain foods and dust on our fingers). And because flame retardants are persistant, they bioaccumulate (they build up over time). They can be measured in our urine and blood. Evidence suggests that flame retardants may be endocrine disruptors, carcinogenic, alter hormone levels, decrease semen quality in men, thyoid disruptors, and act as developmental neurotoxicants (when developing fetus is exposed during pregnancy)  so that children have lowered IQ and more hyperactivity behaviors.

Where are flame retardants found? All around us, and in us. They are so hard to avoid because they're in electronic goods, in upholstered furniture, polyurethane foam, carpet pads, some textiles, the foam in baby items (car seats, bumpers, crib mattresses, strollers,nursing pillows, etc.), house dust, building insulation, and on and on. What to do? Wash hands before eating. Try to use a vacuum cleaner with a HEPA filter. Try to avoid products that say they contain "flame retardants". Only buy upholstered furniture with tags that say they are flame retardant free. From Science Daily:

NYC toddlers exposed to potentially harmful flame retardants

Evidence of potentially harmful flame retardants on the hands and in the homes of 100 percent of a sample of New York City mothers and toddlers has been uncovered by researchers. The study also found that on average toddlers in New York City had higher levels of common flame-retardants on their hands compared to their mothers.

Researchers at the Columbia Center for Children's Environmental Health (CCCEH) within the Mailman School of Public Health report evidence of potentially harmful flame retardants on the hands and in the homes of 100 percent of a sample of New York City mothers and toddlers. The study also found that on average toddlers in New York City had higher levels of common flame-retardants on their hands compared to their mothers. The Center's previous research has linked early life exposure to a common class of flame-retardants called PBDEs with attention problems and lower scores on tests of mental and physical development in children.

Beginning in the 1970s, manufacturers added PBDEs, persistent brominated flame-retardants, to couches, textiles, electronics and other consumer products to comply with flammability standards. They began phasing out PBDEs in 2004 and started using newer alternative flame-retardants, including TBB and TBPH, which are components of the commercial mixture Firemaster 550®. TBB and TBPH are brominated flame retardants for which little is known about their health effects in humans, though they have been linked to reduced fertility and endocrine disruption in animal models.

Researchers visited the homes of 25 mother-child pairs enrolled in the CCCEH Sibling-Hermanos birth cohort, which began in 2008. When children were 3 years old, dust was collected from their homes and hand wipes were collected from the mother and child; these samples were analyzed for flame retardant compounds....Results are consistent with other studies, which demonstrate that toddlers tend to have higher exposure to flame retardants when compared with adults, likely because of the amount of time they spend on the floor.

What exactly are the differences between people with chronic sinusitis and those who are healthy and don't get sinusitis? I've written many times about the Abreu et al 2012 study that found that not only do chronic sinusitis sufferers lack L. sakei, they have too much of Corynebacterium tuberculostearicum (normally a harmless skin bacteria), and they also don't have the bacteria diversity in their sinuses that healthy people without sinusitis have.

In other words, the sinus microbiome (microbial community) is out of whack (dysbiosis). A number of studies found that there is a depletion of some bacterial species, and an increase in "abundance" of other species in those with chronic sinusitis.

Now a new analysis of 11 recent studies comparing people with chronic sinusitis to healthy people adds some additional information. Once again a conclusion was that those with sinusitis had "dysbiosis" (microbial communities out of whack) in their sinus microbiomes when compared to healthy people. And that an increased "abundance" of members of the genus Corynebacterium in the sinuses was associated with chronic sinusitis (studies so far point to C. tuberculostearicum and C. accolens). Nothing new there...

But what was new was that they found that bacteria of the genus Burkholderia and Propionibacterium seem to be "gatekeepers", whose presence may be important in maintaining a stable and healthy bacterial community in the sinuses. And that in chronic sinusitis the bacterial network of healthy communities is "fragmented". In other words, when a person is healthy, the community of microbes in the sinuses may provide a protective effect, and if the gatekeepers are removed (e.g., during illnesses or after taking antibiotics), then a "cycle of dysbiosis and inflammation" may begin.

PLEASE NOTE: Genus is a taxonomic category ranking used in biological classification that is below a family and above a species level. For example, Lactobacillus is the genus and sakei is the species. Also, the researchers discussed "gatekeepers" as being important for sinus health, while Susan Lynch discusses the importance of "keystone species" for sinus health.

OK... so which species of Burkholderia and Propionibacterium bacteria are found in the healthy microbiome? Unfortunately that was not answered in this study. And of course this needs to be tested further to see if the addition of the missing species of Burkholderia and Propionibacterium bacteria to the sinus microbiome will treat chronic sinusitis. Or perhaps other bacteria such as L. sakei and someother still unknown bacteria also need to be added to the mix.

Both Burkholderia and Propionibacterium have many species, but I have not seen any in probiotics. Species of Propionibacteria can be found all over the body and are generally nonpathogenic. However, P. acnes can cause the common skin condition acne as well as other infections.

One species - Propionibacterium freudenreichii (or P. shermanii)  - is found in Swiss type cheeses such as Emmental, Jarlsberg, and Leerdammer. Propionibacteria species are commonly found in milk and dairy products, though they have also been extracted from soil. There are many Burkholderia species, with a number of them causing illness (e.g., B. mallei and B. pseudomallei), but also beneficial species, such as those involved with plant growth and healthBurkholderia species are found all over, in the soil, in plants, soil, water (including marine water), rhizosphere, animals and humans. At this point it is unclear to me which are the species found in healthy sinuses.

But it is clear that while L. sakei works to treat chronic sinusitis in many people, the fact that L. sakei typically has to be used after each illness (cold, sore throat, etc,) means that the sinus microbiome may still be missing microbial species or that there is still some sort of "imbalance" (even though the person may feel totally healthy). The researchers noted that a variety of fungi and viruses are also part of a normal sinus microbiome, but they weren't discussed in the article. As you can see, much is still unknown. Stay tuned..,..

This was a very technical article - thus not easy to read. Keep in mind that the information about the conclusions about the bacteria species in the sinuses was from studies that used modern genetic sequencing data (16S rRNA sequence data) to determine what bacteria are in the sinuses. (These are called "culture independent technologies" and much, much better than using cultures in determining species of bacteria.) This way they could analyze differences in "sinonasal bacterial community composition" and see differences between healthy people and persons with CRS (chronic rhinosinusitis).

Excerpts from Environmental Microbiology: Bacterial community collapse: a meta-analysis of the sinonasal microbiota in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a common, debilitating condition characterized by long-term inflammation of the nasal cavity and paranasal sinuses. The role of the sinonasal bacteria in CRS is unclear. We conducted a meta-analysis combining and reanalysing published bacterial 16S rRNA sequence data to explore differences in sinonasal bacterial community composition and predicted function between healthy and CRS affected subjects. The results identify the most abundant bacteria across all subjects as Staphylococcus, Propionibacterium, Corynebacterium, Streptococcus and an unclassified lineage of Actinobacteria.

The meta-analysis results suggest that the bacterial community associated with CRS patients is dysbiotic and ecological networks fostering healthy communities are fragmented. Increased dispersion of bacterial communities, significantly lower bacterial diversity, and increased abundance of members of the genus Corynebacterium are associated with CRS. Increased relative abundance and diversity of other members belonging to the phylum Actinobacteria and members from the genera Propionibacterium differentiated healthy sinuses from those that were chronically inflamed. Removal of Burkholderia and Propionibacterium phylotypes from the healthy community dataset was correlated with a significant increase in network fragmentation. This meta-analysis highlights the potential importance of the genera Burkholderia and Propionibacterium as gatekeepers, whose presence may be important in maintaining a stable sinonasal bacterial community.

The high density and diversity of host-associated microbial communities present in different body sites supports a near infinite number of potential host to microbe, and microbe to microbe interactions. A stable network of microbial interactions, established through processes such as niche competition, nutrient cycling, immune evasion, and biofilm formation help maintain homeostasis during health (Walter and Ley, 2011; Grice et al., 2009). Taxa that hold together the bacterial community by interacting with different parts of the network can be considered “gatekeepers” (sensu Freeman, 1980; Widder et al., 2014). During health, a consortium of microbes may provide a protective effect, and a breakdown in these networks due to the removal of gatekeepers may begin a self-perpetuating cycle of dysbiosis and inflammation (Vujkovic-Cvijin et al., 2013; Widder et al., 2014; Byrd and Segre, 2016).

The genus-level phylotype Corynebacterium was again associated with CRS bacterial communities, and Burkholderia was associated with healthy subjects.

In contrast to the variety of Actinobacteria and Betaproteobacteria phylotypes differentiating the healthy sinonasal bacterial communities, only one phylotype (Corynebacterium) was consistently associated with those individuals that were chronically inflamed. The significance of specific members of the genus Corynebacterium in CRS microbial communities is supported by findings in two previous studies (Abreu et al., 2012; Aurora et al., 2013). The relative abundance of C. tuberculostearicum and C. accolens was significantly higher in subjects with CRS in two recent 16S rRNA studies (Abreu et al., 2012 and Aurora et al., 2013, respectively). 

Another study finding overdiagnosis (diagnosing something that isn't likely to cause problems) and misdiagnosis (diagnosing something that isn't there) which leads to overtreatment (unnecessary treatment) - this time of asthma in adults. A new study found that as many as 1 in 3 adults diagnosed with asthma may not actually have the disease. Was this due to spontaneous remission or to initial misdiagnosis? After all, many other diseases mimic the symptoms of asthma, and there is no test that can diagnose asthma with 100% accuracy. The study authors thought that of the 33% without asthma - that many of the adults had been originally misdiagnosed, while others had gone into remission. Excerpts from the thought-provoking site Health News Review:

Is it asthma? Many diagnosed with condition receiving unnecessary or incorrect treatment

As many as 1 in 3 adults diagnosed with asthma may not actually have the disease, according to new research published in the Journal of the American Medical Association (JAMA). Canadian researchers evaluated 613 patients with physician-diagnosed asthma and found that 203 participants (33%) most likely did not have the disease. After an additional 12 months of follow-up of this latter group, 181 subjects (30%) continued to exhibit no clinical or laboratory evidence of asthma.

This study, and its accompanying editorials, hit on a theme we’ve often raised with regard to cancer and many other chronic diseases: overdiagnosis leading to overtreatment. But it also raises the specter of misdiagnosis from the get-go, which can lead to erroneously treating a condition that isn’t there. The Canadian results may also confuse many of us who have grown accustomed to news stories warning us that asthma is on the rise. So which is it? More asthma which needs more aggressive treatment or less asthma warning against overtreatment?

“I think asthma is both overdiagnosed and underdiagnosed,” says Dr. Nancy Ott, an allergy and immunology specialist in practice for 28 years. “We don’t have a specific test that is definitive for asthma, and the diagnosis is nuanced. You need to look at the symptoms, the patient’s history, their family history, and the objective tests collectively. And I think we need to be much more strict in what constitutes asthma because the symptoms alone overlap with so many other conditions.”

This is not a message we hear nearly enough in news stories: the diagnosis of asthma, although common, is anything but cut-and-dried. In outpatient clinics – where most asthma is diagnosed – time pressures can lead to incomplete evaluations, which lead to misdiagnoses (which, by the way, includes over-, under-, and no diagnoses), and this can ultimately lead to patients suffering physically, emotionally and financially.

“We think that a large proportion of them had been misdiagnosed in the first place and another proportion that (was) a bit smaller had actually gone into remission, their asthma was no longer active,” said principal investigator Dr. Shawn Aaron, head of respirology at the University of Ottawa. Medical textbooks say about six per cent of people with asthma go into remission over a 10-year period, said Aaron. “But we found at least 20 per cent had gone into remission.” However, “one of the main messages I want to get across is that some people are being misdiagnosed because they’re not being properly investigated to begin with,” he said from Ottawa.

Which brings up an important point: the symptoms of asthma overlap with several other diseases. In the Canadian study, 12 people, or 2 percent of the participants, had serious conditions other than asthma, like heart disease and pulmonary hypertension. Others had problems such as hyperventilation from panic attacks, and gastroesophageal reflux (GERD). These latter two conditions frequently mimic asthma. As does vocal cord dysfunction. Suffice to say that if you were to take each of the classic symptoms of asthma individually, the list of diseases associated with that symptom is well over a dozen.

Worried about whether being physically active just on weekends can make a difference in health if the rest of the week is spent sitting all day? Well, there is good news! Being a "weekend warrior" (one who exercises or is active only one or two days a week) may also offer health benefits according to a new study (associated with lower death rates from all causes, cancer, and cardiovascular disease).

Current government guidelines recommend at least 150 minutes per week of moderate-intensity activity (such as brisk walking or tennis), or at least 75 minutes per week of vigorous activity (such as jogging or swimming laps), or equivalent combinations of moderate and vigorous physical activity. From Science Daily:

'Weekend warriors' have lower risk of death from cancer, cardiovascular disease

Physical activity patterns characterized by just one or two sessions a week may be enough to reduce deaths in men and women from all causes, cardiovascular disease (CVD) and cancer, regardless of adherence to physical activity guidelines, a new study of over 63,000 adults reports. The finding suggests that less frequent bouts of activity, which might fit more easily into a busy lifestyle, offer significant health benefits, even in the obese and those with medical risk factors.

Regular physical activity is associated with lower risks of death from all causes, cardiovascular disease and cancer, and has long been recommended to control weight, cholesterol, and blood pressure. The World Health Organization recommends that adults do at least 150 minutes per week of moderate-intensity activity, or at least 75 minutes per week of vigorous-intensity activity, or equivalent combinations.

But research is yet to establish how the frequency and total weekly dose of activity might best be combined to achieve health benefits. For example, individuals could meet current guidelines by doing 30 minutes of moderate-intensity physical activity five days of the week or 75 minutes of vigorous-intensity physical activity on just one day of the week. Those who do all their exercise on one or two days of the week are known as 'weekend warriors'. 

A few days ago the CDC (Centers for Disease Control and Prevention) released a report about a Nevada woman who died in August 2016 of a bacterial infection that was resistant to all 26 antibiotics available in the US, including the antibiotic of last resort - colistin. Apparently she had picked up the bacterial infection in India, where she been staying for an extended visit and where she had been hospitalized (a fractured leg, which led to a hip infection). Because of the antibiotic resistance, the infection spread, and she went into septic shock and died.

India has soaring rates of antibiotic resistance due to misuse of antibiotics (or antimicrobials). But this is not just a problem with infections acquired in India, but throughout the world. Antibiotic resistance is increasing everywhere (post with video of how superbugs evolve). This is because bacteria are constantly evolving against the antibiotics they're exposed to. We may reach a point where simple cuts or infections could lead to death because no antibiotics will work. The World Health Organization said in a 2014 report that: "The problem is so serious that it threatens the achievements of modern medicine. A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the twenty-first century."

New antibiotic development is not keeping pace with the emergence of new antibiotic resistant bacteria. According to the CDC: "Each year in the United States, at least 2 million people become infected with bacteria that are resistant to antibiotics and at least 23,000 people die each year as a direct result of these infections." On top of that, too few antibiotics are under development, and those antibiotics tend to be developed by small companies, not the big pharmaceutical companies. Farmers are still giving antibiotics (antimicrobials) to farm animals unnecessarily, typically as "growth promoters" or to try to prevent disease. The sale of antibiotics routinely fed to animals has been increasing in recent years, and currently about 80% of all antibiotics used in the US are given to livestock animals (of which nearly 70 percent of those used are considered “medically important” for humans).

Excerpts from The Atlantic: A Woman Was Killed by a Superbug Resistant to All 26 American Antibiotics

Yesterday morning, I published a story about the silent spread of resistance against the antibiotic of last resort, colistin—a major step toward the emergence of a superbug resistant to all antibiotics. While reporting this story, I interviewed Alex Kallen, an epidemiologist at the CDC, and I asked if anyone had found such a superbug yet. “Funny you should ask,” he said.

Funny—by which we all mean scary—because yesterday afternoon, the CDC also released a report about a Nevada woman who died after an infection resistant to 26 antibiotics, which is to say all available antibiotics in the U.S. The woman, who was in her 70s, had been previously hospitalized in India after fracturing her leg, eventually which led to an infection in her hip. There was nothing to treat her infection—not colistin, not other last-line antibiotics. Scientists later tested the bacteria that killed her, and found it was somewhat susceptible to fosfomycin, but that antibiotic is not approved in the U.S. to treat her type of infection.

Looks like exercise, even 20 minutes of moderate activity such as brisk walking, has beneficial anti-inflammatory health effects. Inflammation is part of the body's normal immune response - it is the body's attempt to heal itself after an injury and tissue damage, and to defend itself against infection from foreign invaders, such as viruses and bacteria.

However, chronic inflammation (e.g., what can occur in obesity, diabetes, and poor lifestyle) can lead to serious health issues and is linked to cancer, heart disease, etc. So lowering chronic (systemic) inflammation is good. From Science Daily:

Exercise ... It does a body good: 20 minutes can act as anti-inflammatory

It's well known that regular physical activity has health benefits, including weight control, strengthening the heart, bones and muscles and reducing the risk of certain diseases. Recently, researchers at University of California San Diego School of Medicine found how just one session of moderate exercise can also act as an anti-inflammatory. The findings have encouraging implications for chronic diseases like arthritis, fibromyalgia and for more pervasive conditions, such as obesity.

The study, recently published online in Brain, Behavior and Immunity, found one 20-minute session of moderate exercise can stimulate the immune system, producing an anti-inflammatory cellular response. The brain and sympathetic nervous system -- a pathway that serves to accelerate heart rate and raise blood pressure, among other things -- are activated during exercise to enable the body to carry out work. Hormones, such as epinephrine and norepinephrine, are released into the blood stream and trigger adrenergic receptors, which immune cells possess. This activation process during exercise produces immunological responses, which include the production of many cytokines, or proteins, one of which is TNF -- a key regulator of local and systemic inflammation that also helps boost immune responses.

The 47 study participants walked on a treadmill at an intensity level that was adjusted based on their fitness level. Blood was collected before and immediately after the 20 minute exercise challenge."Our study shows a workout session doesn't actually have to be intense to have anti-inflammatory effects. Twenty minutes to half-an-hour of moderate exercise, including fast walking, appears to be sufficient," said Hong.

Inflammation is a vital part of the body's immune response. It is the body's attempt to heal itself after an injury; defend itself against foreign invaders, such as viruses and bacteria; and repair damaged tissue. However, chronic inflammation can lead to serious health issues associated with diabetes, celiac disease, obesity and other conditions.

 More research supporting that the appendix has a purpose - that it has an immune function and is a "reservoir" for beneficial gut bacteria. That is, it is where beneficial bacteria go and hide out when the person has food poisoning or is taking antibiotics (which wipe out bacteria in the gut), and then these bacteria replenish the gut afterwards. (Other supporting research.) This is the opposite of what many have believed for years (and we were taught in school) - which was that it is something that may have had a purpose long ago, but now is a "vestigial organ" and useless in humans. Hah! Once again scientific knowledge is being rewritten.

The researchers examined 533 mammal species for the presence of an appendix, and found it in a number of them, including humans, chimps, and dogs. From Science Daily:

Appendix may have important function, new research suggests

The human appendix, a narrow pouch that projects off the cecum in the digestive system, has a notorious reputation for its tendency to become inflamed (appendicitis), often resulting in surgical removal. Although it is widely viewed as a vestigial organ with little known function, recent research suggests that the appendix may serve an important purpose. In particular, it may serve as a reservoir for beneficial gut bacteria. Several other mammal species also have an appendix, and studying how it evolved and functions in these species may shed light on this mysterious organ in humans.

Heather F. Smith, Ph.D., Associate Professor, Midwestern University Arizona College of Osteopathic Medicine, is currently studying the evolution of the appendix across mammals. Dr. Smith's international research team gathered data on the presence or absence of the appendix and other gastrointestinal and environmental traits for 533 mammal species. 

They discovered that the appendix has evolved independently in several mammal lineages, over 30 separate times, and almost never disappears from a lineage once it has appeared. This suggests that the appendix likely serves an adaptive purpose. Looking at ecological factors, such as diet, climate, how social a species is, and where it lives, they were able to reject several previously proposed hypotheses that have attempted to link the appendix to dietary or environmental factors. Instead, they found that species with an appendix have higher average concentrations of lymphoid (immune) tissue in the cecum. This finding suggests that the appendix may play an important role as a secondary immune organ. Lymphatic tissue can also stimulate growth of some types of beneficial gut bacteria, providing further evidence that the appendix may serve as a "safe house" for helpful gut bacteria.

 Drawing of colon seen from front (the appendix is colored red). From Wikipedia

Another large study looking at screening mammograms for breast cancer has raised the issue of overdiagnosis and overtreatment once again. The purpose of mammography screening is to find cancer when it is small and so prevent cancer from growing and becoming advanced cancer. However, the researchers did not find this - there was a major increase in finding small cancers (the kind that may grow so slowly as to never cause any problems or that may even regress), but the rate of advanced cancers stayed the same.

The problem of overdiagnosis (finding small tumors that may never cause problems) and overtreatment (treating unnecessarily), which is leading to medical experts "rethinking cancer screening" is a major shift in how cancer screening is being viewed for a number of cancers. This is because studies show that overall death rates are basically the same in screened vs non-screened persons for mammography, colon, prostate, and lung cancer screening (see post). The view of how cancer grows and spreads may have to be reexamined and changed. One possibility suggested by Dr. H. Gilbert Welch is that aggressive cancer is already "a systemic disease by the time it's detectable" (Oct. 28, 2015 post).

The following excerpts are from the thoughtful review of the study in Health News Review: Overdiagnosis of ductal carcinoma in situ: ‘the pathology equivalent of racial profiling’

Danish researchers are providing new evidence that many breast cancers found via screening mammograms don’t need to be treated. Women with these non-threatening tumors are said to be “overdiagnosed” with breast cancerOverdiagnosis occurs when breast screening such as mammography detects small, slow-growing cancers that may never cause the patient any trouble. Yet, women diagnosed with such tumors are exposed to very real harms–possible surgery, chemotherapy, radiation, and living life as a “cancer patient.”

How much overdiagnosis are we talking about? If you don’t include cases of ductal carcinoma in situ (DCIS) in the tallies, anywhere from 14.7% to 38.6% of breast cancers found via screening represent overdiagnosis, the study authors found. The rate ranges from 24.4% to as high as 48.3% when DCIS is included.

DCIS is a collection of abnormal cells inside a milk duct that may–but usually doesn’t–break out to become invasive and potentially lethal cancer. About 60,000 women are told they have DCIS each year in the United States. Some experts estimate that up to 80% of women with DCIS found via screening may not need any treatment at all–and instead should just keep an eye on things. Obviously, women need to be fully and accurately informed about the benefits and risks — including the risk of overdiagnosis — before embarking on any decision to get screened for breast cancer or choosing a course of action following a diagnosis.

Otis Brawley, MD, Chief Medical Officer for the American Cancer Society, says it’s been difficult for modern medicine to wrap its brain around the concept of overdiagnosis. The natural inclination is to assume that cancerous-looking cells “will grow, spread, and eventually kill,” he writes in an editorial accompanying the Danish study. “However, some of these lesions may be genomically predetermined to grow no further and may even regress. In many respects, considering all small breast lesions to be deadly and aggressive types of cancer is the pathologic equivalent of racial profiling.

Excerpts from the original study from the Annals of Internal Medicine: Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis

Background: Effective breast cancer screening should detect early-stage cancer and prevent advanced disease. Objective: To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant).... Setting: Denmark from 1980 to 2010. Participants: Women aged 35 to 84 years. Intervention: Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times.

Conclusion: Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS (ductal carcinoma in situ) diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%).

Breast screening is associated with a substantial increase in the incidence of nonadvanced tumors and DCIS (ductal carcinoma in situ) in Denmark but not with a reduction in the incidence of advanced tumors, and the overdiagnosis rate is substantial. These findings support that screening has not accomplished the promise of a reduction in invasive therapy or disease-specific mortality.