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Published on Leave a comment on Should We Be Worried That Humans Are Losing Many Species of Gut Microbes?

An article was just published in a research journal to discuss the fact that humans - in part due to lifestyles which include less dietary fiber (due to eating fewer varieties and amounts of plants) and due to medical practices (such as frequent use of antibiotics) has resulted in gut "bacterial extinctions". In other words, humans (especially those living an urban industrialized Western lifestyle) have fewer gut bacterial species than those living a more traditional lifestyle, and this loss of bacterial species is linked to various diseases. Humans can increase the number of certain bacterial species, but the loss of some bacterial species is forever. 

The researchers discuss that humans have the "lowest level of gut bacterial diversity"  of any hominid and primate. They stated that the shrinking of the variety of microbial species in the human gut (the gut microbiome) began early in human evolution (as humans started eating more meat), but that it has accelerated dramatically within industrialized societies. And that evidence is accumulating that this gut bacterial "depauperation" - the loss of a variety of bacterial species - may predispose humans to a range of diseases.  Some of it is due to evolution (as humans ate more meat), and some to lifestyle changes. A term is used throughout this paper: depauperate - which means lacking in numbers or variety of species in the gut microbiome (the microbial community or ecosystem).

Other research has also shown that eating a highly processed Western diet results in gut microbial changes that are linked to various diseases (here, here, here) - that is, the microbes being fed are those associated with diseases. Also, certain diets encourage certain microbial species to flourish (here, here).  Bottom line: studies find health benefits from higher levels of dietary fiber - from fruits, vegetables, seeds, nuts, whole grains, and legumes (beans). From Current Opinion In Microbiology:

The shrinking human gut microbiome

Highlights: Humans harbor the lowest levels of gut bacterial diversity of any hominid. Humans in industrialized nations harbor fewer gut bacterial taxa than any primate. Medical practices and lack of dietary fiber may drive gut bacterial extinctions. Depauperate microbiotas may predispose entire human populations to certain diseases.

Mammals harbor complex assemblages of gut bacteria that are deeply integrated with their hosts’ digestive, immune, and neuroendocrine systems. Recent work has revealed that there has been a substantial loss of gut bacterial diversity from humans since the divergence of humans and chimpanzees. This bacterial depauperation began in humanity’s ancient evolutionary past and has accelerated in recent years with the advent of modern lifestyles. Today, humans living in industrialized societies harbor the lowest levels of gut bacterial diversity of any primate for which metagenomic data are available, a condition that may increase risk of infections, autoimmune disorders, and metabolic syndrome. Some missing gut bacteria may remain within under-sampled human populations, whereas others may be globally extinct and unrecoverable.

A typical human harbors on the order of 1013 bacterial cells in the large intestine. This gut microbiota, which can contain over a thousand species, is deeply integrated with virtually every tissue and organ system in the body. Gut bacteria process difficult to digest components of the diet, promote angiogenesis in the intestine, train the immune system, regulate metabolism, and even influence moods and behaviors.

In contrast to hunter–gatherer to agricultural transitions, adoptions of industrial and post-industrial lifestyles have led to massive reductions in bacterial richness within human gut microbiotas. Individuals living in urban centers in the United States harbor fewer gut bacterial species on average than do individuals living more traditional lifestyles in Malawi , Venezuela, Peru, and Papua New Guinea.....Industrialized and traditional lifestyles differ in many respects, confounding the identification of the specific practices that have led to decreases in gut bacterial diversity within industrialized societies. One potential cause is the rise of food processing and the corresponding reductions in the intake of dietary fiber in favor of simple sugars. Recently, studies in model systems have indicated that long-term reductions in dietary fiber can lead to the extirpation of gut bacterial taxa from host lineages. 

Other potential causes of reduced gut bacterial diversity within industrialized human populations include certain modern medical practices. For example, longitudinal studies in humans have shown that levels of gut bacterial diversity decrease drastically after antibiotic use. Although bacterial richness may recover after treatment is completed, the timeline and extent of the restoration is highly subject-dependent. The consequences of antibiotic use on gut bacterial diversity may be most severe when treatment is administered during the early years of life, before the adult microbiota has fully formed .

Published on Leave a comment on Four Years of Sinusitis Treatment Success

It's now 4 years being free of chronic sinusitis and off all antibiotics! Four amazing years since I (and then the rest of my family) started using easy do-it-yourself sinusitis treatments containing the probiotic (beneficial bacteria) Lactobacillus sakei. My sinuses feel great! And yes, it still feels miraculous.

After reading the original ground-breaking research on sinusitis done by Abreu et al (2012), it led to finding and trying L. sakei as a sinusitis treatment. Of course, there is an entire community of microbes (bacteria, fungi, viruses) that live in healthy sinuses - the sinus microbiome - but L. sakei seems to be a key one for sinus health.

I just updated the post The One Probiotic That Treats Sinusitis (originally posted January 2015) using my family's experiences (lots of self-experimentation!) and all the information that people have sent me. The post has a list of brands and products with L. sakei, treatment results, as well as information about some other promising probiotics (beneficial bacteria). Thank you so much!

Thank you all who have written to me  - whether publicly or privately. Please keep writing and tell me what has worked or hasn't worked for you as a sinusitis treatment. If you find another bacteria or microbe or product that works for you - please let me know. It all adds to the sinusitis treatment knowledge base. I will keep posting updates. 

(NOTE: I wrote our background story - Sinusitis Treatment Story back in December 2013, there is also an updated  Sinusitis Treatment Summary page with the various treatment methods quickly discussed, and latest information on everything: The Best Probiotic For Sinus Infections. One can also click on SINUSITIS under CATEGORIES to see more posts about what is going on in the world of sinusitis research.)

Published on Leave a comment on New Antibiotics Are Needed For Twelve Scary Superbugs

Image result for Acinetobacter baumannii Many posts on this blog are about beneficial microbes, and the many species of microbes (bacteria, fungi, viruses) living within and on us. But there are also bacteria in the world that pose a serious threat to human health, and the list of these are growing due to antibiotic resistance. This week the World Health Organization (WHO) officials came out with a list of a dozen antibiotic-resistant "priority pathogens" that pose the greatest threats to human health. These are bacteria resistant to multiple antibiotics - thus superbugs.

Antibiotic resistance is increasing due to misuse of antibiotics (or antimicrobials), and this is occurring throughout the world (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."

Part of the problem is that farmers are still giving antibiotics (antimicrobials) to farm animals unnecessarily, typically as "growth promoters" or to try to prevent disease. 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).

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."

According to WHO officials "The bacteria on the list are responsible for severe infections and high mortality rates mostly in hospitalized patients, transplant recipients, those receiving chemotherapy or patients in intensive care units." They have also been seen in our hospitalized and returning military service people. The WHO list is meant to steer public and private research dollars toward developing new antibiotics for these particular families of bacteria. Pharmaceutical companies currently lack financial incentives to develop new drugs aimed at these superbugs. Currently too few new antibiotics are under development. From World Health Organization:

WHO publishes list of bacteria for which new antibiotics are urgently needed

WHO today published its first ever list of antibiotic-resistant "priority pathogens" – a catalogue of 12 families of bacteria that pose the greatest threat to human health. The list was drawn up in a bid to guide and promote research and development (R&D) of new antibiotics, as part of WHO’s efforts to address growing global resistance to antimicrobial medicines. The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics. These bacteria have built-in abilities to find new ways to resist treatment and can pass along genetic material that allows other bacteria to become drug-resistant as well.....The WHO list is divided into three categories according to the urgency of need for new antibiotics: critical, high and medium priority.

The most critical group of all includes multidrug resistant bacteria that pose a particular threat in hospitals, nursing homes, and among patients whose care requires devices such as ventilators and blood catheters. They include Acinetobacter, Pseudomonas and various Enterobacteriaceae (including Klebsiella, E. coli, Serratia, and Proteus). They can cause severe and often deadly infections such as bloodstream infections and pneumonia. These bacteria have become resistant to a large number of antibiotics, including carbapenems and third generation cephalosporins – the best available antibiotics for treating multi-drug resistant bacteria. The second and third tiers in the list – the high and medium priority categories – contain other increasingly drug-resistant bacteria that cause more common diseases such as gonorrhoea and food poisoning caused by salmonella.

WHO priority pathogens list for R&D of new antibiotics: Priority 1: CRITICAL - Acinetobacter baumannii, carbapenem-resistant, Pseudomonas aeruginosa, carbapenem resistant, Enterobacteriaceae, carbapenem-resistant, ESBL-producing. Priority 2: HIGH - Enterococcus faecium, vancomycin-resistant, Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant, Helicobacter pylori, clarithromycin-resistant, Campylobacter spp., fluoroquinolone-resistant, Salmonellae, fluoroquinolone-resistant, Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant. Priority 3: MEDIUM - Streptococcus pneumoniae, penicillin-non-susceptible, Haemophilus influenzae, ampicillin-resistant, Shigella spp., fluoroquinolone-resistant.

Image result for Acinetobacter baumannii Acinetobacter baumannii  Credit: Centers for Disease Control and Prevention (CDC)

Published on Leave a comment on All Babies Have Fungi Living In Them

A new study has summarized what we know about fungi that live in and on babies - and yes, we all have fungi both on and within us. It's called the mycobiome. In healthy individuals all the microbes (bacteria, viruses, fungi, etc) live in balanced microbial communities, but the communities can become "out of whack" (dysbiosis) for various reasons, and microbes that formerly co-existed peacefully can multiply and become problematic. Or other pathogenic microbes can enter the community, and the person becomes ill.

In healthy adults, approximately 0.1% of the microbes in the adult intestine are fungi, from approximately 60 unique species. Most species live peacefully in the body, and some fungi even have health benefits (e.g., Saccharomyces boulardii prevents gastrointestinal disease). Some fungi that many view as no good and involved with diseases (e.g., Candida and Aspergillus) are also found normally in healthy people. Studies show that normally infants also have fungi. Some fungi that live in the baby's gut (thus detected in fecal samples) are Candida (including C. albicans), Saccharomyces, and Cladosporium. The researchers (from the Univ. of Minnesota) point out that the study of fungi in babies has been neglected and much more research needs to be done.

Whether an infant is born vaginally or through cesarean delivery (C-section) affects the composition of the baby's bacterial communities over the first 6 months of life. And similarly, it looks like when the baby passes through the birth canal, the baby is exposed to the mother's mycobiota (fungi), and then these colonize in the infant's gut. Babies born by C-section have some differences in their fungi, such as being colonized by the mother's skin fungi (such as Malassezia fungi). After birth, a parent kissing and touching the baby (skin to skin contact) also transmits microbes, including fungi, to the baby.

Whether a baby drinks breast milk or formula strongly affects the infant's bacteria within the GI tract. For example, breast-fed infants have more Bifidobacteria and Labctobacilli in their gut compared to formula-fed infants. One study found about 700 species of bacteria in breast milk. Thus, scientists think that human breast milk also influences the infant gut mycobiota (fungi), although this research still needs to be done.

Whether a baby is born prematurely or at term (gestational age) is important. For infants born prematurely, intestinal fungi can cause big problems, such as an overgrowth in the gut. For example, 10% of premature babies get invasive, systemic Candidiasis, and about 20% die. Some factors leading to this are: a naïve immune system, bacterial communities out of whack (dysbiosis) due to antibiotic exposure, and use of parenteral nutrition (because this doesn't contain all the microbes from the mother that are in breast milk). In premature infants, beneficial fungi such as S. boulardii, may help to regulate the growth of opportunistic fungal colonizers such as Candida.

it is clear that whether the baby received antibiotics is important. The bacterial community of infants is altered by exposure to antibiotics in both term and preterm infants. For example, in a lengthy study over the first 3 years of life, infants receiving multiple courses of antibiotics had bacterial community changes following antibiotics and their gut bacterial microbiome became less diverse (fewer species). Although most commonly used antibiotics do not directly act on fungi, anti-bacterial antibiotic exposure is associated with alterations to the mycobiota (fungi) -  such as increased rates of fungal colonization, fungal overgrowth, and changes in the fungal community. For ex., premature infants exposed to cephalosporin antibiotics have an increased risk for invasive Candidiasis (a fungal overgrowth).

Out of whack (dysbiotic) microbial communities, incuding fungi, are found in IBD (intestinal bowel diseases) in children. They have more of some fungi (e.g. Pichia jadinii and Candida parapsilosis) and less of Cladosporium cladosporiodes, and an overall decrease in fungal diversity in the gut, as compared to healthy children.

From BMC Medicine: Infant fungal communities: current knowledge and research opportunities

The microbes colonizing the infant gastrointestinal tract have been implicated in later-life disease states such as allergies and obesity. Recently, the medical research community has begun to realize that very early colonization events may be most impactful on future health, with the presence of key taxa required for proper immune and metabolic development. However, most studies to date have focused on bacterial colonization events and have left out fungi, a clinically important sub-population of the microbiota. A number of recent findings indicate the importance of host-associated fungi (the mycobiota) in adult and infant disease states, including acute infections, allergies, and metabolism, making characterization of early human mycobiota an important frontier of medical research. This review summarizes the current state of knowledge with a focus on factors influencing infant mycobiota development and associations between early fungal exposures and health outcomes. We also propose next steps for infant fungal mycobiome research....

Published on Leave a comment on Environmental Pollutants and Gut Microbes

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).

Published on Leave a comment on Woman Dies From Superbug Resistant To 26 Antibiotics

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.

Published on Leave a comment on Poop Pills Work!

The latest development in treating stubborn cases of Clostridium difficile infections (CDI) are "poop pills" - pills that patients can easily swallow rather than having to go through a fecal microbiota transplant (FMT). The "poop pills" are filled with blenderized fecal matter from healthy donors, are much easier for patients to swallow, and they successfully treat C. difficile at almost the same rate as fecal microbiota transplants - about 91% after 1 or 2 treatments for the pills, and 93 to 96% for FMT. This is an amazing success rate for an infection that debilitates people, is resistant to antibiotics in many cases, and even kills people.

Interestingly, these "poop pills" or "Capsule FMT" containing an entire microbiome (bacteria, viruses, fungi, etc) had fantastic results, as compared to a probiotic for the treatment of C. difficile tested by microbiome therapeutics company Seres Therapeutics Inc. In July 2016 Seres announced very disappointing results (no better than a placebo) with its product known as SER-109, a mix of various strains of bacteria.

So why did the Seres probiotic not work in clinical trails? The answer seems to be that the human gut (and so also human fecal matter) contains an entire community of microbes - hundreds of species of bacteria, as well as fungi, viruses, and archaea, but the Seres probiotic was just a mixture of some types of bacteria. This shows how little we know right now. (NOTE: For those interested, the "poop pills" or Capsule FMT is now offered as standard care for recurrent CDI at Massachusetts General Hospital.) From BioMedCentral:

Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection

Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up. We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8 weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above.

Overall, 180 patients aged 7–95 years with a minimal follow-up of 8 weeks were included in the analysis. CDI resolved in 82 % of patients after a single treatment, rising to a 91 % cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed. We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.

The epidemiology of Clostridium difficile infection (CDI) is evolving. Rates of infection are increasing and response to standard antimicrobial treatment with metronidazole or vancomycin may be suboptimal [1, 2].....Fecal microbiota transplant (FMT) has been shown to be safe and effective in treating refractory or relapsing CDI [4, 5, 6, 7, 8], but its use has been limited by practical barriers. Among other concerns, the administration of FMT by colonoscope or naso-gastric/duodenal tube exposes the patient to some risk and discomfort. We recently reported a preliminary feasibility study using orally administered frozen fecal capsules, prepared from unrelated donors, to treat 20 patients with recurrent CDI [9]. Following these encouraging results, we have continued treating patients with FMT capsules. We report our clinical experience in a large cohort with structured follow-up.

Donated fecal matter was blenderized, sieved, centrifuged, and suspended in concentrated form in sterile saline with 10 % glycerol. The suspension was double-encapsulated in hypromellose capsules (Capsugel, Cambridge, MA) and stored at –80 °C for up to 6 months pending use. Processing was done entirely under ambient air. FMT recipients discontinued any anti-CDI treatment for 24–48 hours prior to FMT, and were given 15 capsules on each of two consecutive days with water or apple sauce. The 30 capsules contained sieved, concentrated material derived from a mean of 48 g of fecal matter.

Of the 180 patients reaching 8 weeks, 147 were cured of CDI after the first administration of fecal capsules (82 %). Twenty six individuals relapsed within 8 weeks and were re-treated, with 17 responding, resulting in an overall cure rate of 91 % with one or two treatments. Six individuals declined re-treatment (our standard procedure in these cases is to offer long-term suppressive oral vancomycin treatment). Three patients were cured after a third administration, but were considered “non-responders” as per protocol definition. One patient received three treatments, relapsed, and was advised to continue suppressive vancomycin.

Published on Leave a comment on The Development of Antibiotic Resistant Bacteria

Here is an amazing short video for those interested in seeing how bacteria mutate and grow when exposed to antibiotics - and evolving to become superbugs. Researchers filmed an experiment that created bacteria a thousand times more drug-resistant than their ancestors. In the time-lapse video, a white bacterial colony (E.coli bacteria) creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibacterial drugs (antibiotics).

How they did it: The researchers imaged the E. coli bacteria every 10 minutes for 10 days as the microbes expanded across the plate. You can see that the bacteria paused briefly at the boundaries of increasingly stronger antibiotic concentrations until a mutant bacteria struck out into the stronger antibiotic territory. By challenging the bacteria with differing doses of antibiotic, the team demonstrated that E. coli evolve higher resistance more quickly if they first encounter an intermediate, rather than a high, concentration of antibiotic. It's a beautiful, yet horrifying video. NOTE: the bacteria grows on agar, which is a thick, clear substance that comes from seaweed and is used for growing bacteria in scientific research. From Harvard Medical School, on YOUTUBE:

From NPR:  WATCH: Bacteria Invade Antibiotics And Transform Into Superbugs

In the time-lapse video, a white bacterial colony creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibiotic. The colony pauses when it hits the first band of antibiotic, creating a stark border between the white colony and the black petri dish. Then the bacteria start to edge their way into the toxic soup. More dots appear and they start growing, racing to the next, stronger band of antibiotic. The bacteria are evolving. After almost two weeks of real time have passed, they've become resistant to the strongest completely taken over the kitchen-table-sized petri dish.

We know dangerous bacteria are getting stronger all the time and that it's our fault because of our excessive and indiscriminate use of antibiotics. Each year, 23,000 people in the U.S. die as a result of superbug infections. But we typically don't get to see superbugs created.... Their video and report were published Thursday in the journal Science. 

Published on Leave a comment on Paradigm Shift In Thinking About Urinary Tract Infections

This article by Dr. Thomas E. Finucane lays out nicely a paradigm shift in how to view uncomplicated urinary tract infections (UTIs) - as a case of dysbiosis (microbial community out of whack), and that antibiotics to kill bacteria are generally not needed or helpful. (He doesn't mention it, but the next step in his argument should be that probiotic or beneficial bacteria or other microbes may improve the microbial community and symptoms.) A main point of the article is that we now know the urinary tract is not sterile - instead diverse microbiota live there (the microbial community is the microbiome) including bacteria and viruses (the virome), and that these stable microbial communities are generally beneficial. Standard cultures do not pick up all the microbes living in the urinary tract.

He points out that: UTI symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis (which does need antibiotic treatment); and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment. He stresses the "generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the years who have suffered “UTI” without access to antibiotics and have recovered fully". And that "urinary tract dysbiosis" may be a better description of what a woman is experiencing.

However, I would like to add that to a person experiencing an UTI, the pain does not at all feel "benign". So look at the posts on UTIs and treatments and perhaps try something like D- mannose  or cranberry supplements, or both. From The American Journal of Medicine:

“Urinary tract infection” and the microbiome

The current paradigm for managing uncomplicated “urinary tract infection” (“UTI”) is deeply flawed. “UTI” is ambiguously defined and, coupled with a belief that “bacteria are not normal inhabitants of the urinary tract, the diagnosis often leads to unnecessary, harmful antibiotic treatment. Although bacteriuria identified by standard clinical cultures (which we will call standard bacteriuria) is central to most definitions, more sensitive diagnostic tests now demonstrate that “urine is not sterile”2 and that standard bacteriuria represents a fraction of the diverse microbiota hosted by the urinary tract. Knowledge of this complex, generally beneficial microbiome deeply undermines the current paradigm, which relies on the findings of standard culture. By acknowledging this microbiome a successor paradigm will generate new questions about relationships among host, microbiome and antibiotic use and will almost surely show additional serious harms from antibiotic overtreatment.

This discussion concerns medically stable, non-pregnant adults with normal urinary tract structure and function. The role of antibiotics in patients with abnormalities of anatomy or physiology, such as spinal cord injury, urinary obstruction, or catheters, will require careful investigation. New insight into pyelonephritis and bacteremic bacteriuria is likely to develop.

The ambiguous definition of “UTI” seems to promote antibiotic overuse. In one common usage, “urinary tract infection is defined as microbial infiltration of the normally sterile urinary tract.” With this definition, asymptomatic bacteriuria is a “UTI” and is often treated, even in patient groups where strong evidence shows lack of benefit.4 A second common definition, “significant bacteriuria in a patient with symptoms or signs attributable to the urinary tract and no alternate source” seems more restrictive but does not define what symptoms or signs may be attributed to the urinary tract. This ambiguity creates opportunities for overtreatment....Antibiotic treatment of “UTI” often follows even though no data have shown these changes respond to treatment.

Canonically, “all symptomatic UTI should be treated” but actual benefit is limited. Hooton emphasizes that in acute uncomplicated cystitis “the primary goal of treatment is to ameliorate symptoms.” Foxman summarizes that symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis; and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment.7 The generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the eons who have suffered “UTI” without access to antibiotics and have recovered fully.

With its various meanings, convenient diagnosis, long tradition, suggestive link to treatment and uncritical acceptance by clinicians, patients, families and insurers, “UTI” remains heavily embedded in practice, “one of the most common bacterial infections worldwide”. The paradigm provides tidy management for a patient with “UTI” who expects antibiotics. Further, the current paradigm does account for several findings. Standard bacteriuria is associated with pyuria, fever and dysuria, for example, and these often improve with treatment, as do a wide variety of findings seemingly unconnected with the urinary tract. Antibiotic treatment improves outcomes for asymptomatic pregnant women who have standard bacteriuria. Pyelonephritis and bacteremic bacteriuria probably arise in the urinary tract and do require antibiotic treatment.

To diagnose “UTI” and determine antibiotic sensitivity based on results of standard cultures, however, is to rely on familiar, accessible data and to ignore the dozens of bacterial species, as well as intracellular bacterial colonies and urinary virome known to reside in the urinary tract. Current discussions of symptomatic or asymptomatic bacteriuria or sterile urine are similarly problematic. To attribute delirium to standard bacteriuria seems unjustifiable, knowing that most or all people with or without delirium have bacteriuria. The current paradigm is defensible only if all pathogenic organisms are identified with standard cultures and all organisms more difficult to identify can be safely ignored.

We propose instead that urinary symptoms, bacteremia, pyelonephritis, and other recognizable disturbances of the urinary tract are the dysbiotic tip of a much larger iceberg of complex host-microbe interactions that are occurring out of sight of standard cultures. As expected in the era of the microbiome, stable bacterial communities are generally beneficial. For example, compared with the instillation of sterile saline, “bladder colonization with (the nonpathogenic) E. coli HU2117 safely reduces the risk of symptomatic urinary tract infection in patients with spinal cord injury”.8 Of 699 young women with asymptomatic bacteriuria, half of whom were randomized to receive no antibiotic treatment, “treatment was associated with a higher rate of symptomatic UTI… (thus) asymptomatic bacteriuria … may play a protective role in preventing symptomatic recurrence” during 12-month follow-up.9

Costello and colleagues outline a broader paradigm shift in the general approach to infection; “transitioning clinical practice from the Body-as-Battleground to the Human-as-Habitat perspective will require rethinking how one manages the human body.”10 To help in this transition, mindful language will be important. We suggest that authors use “UTI” only within quotation marks and that clinicians use the bimanual “air quotes” gesture in discussions. This small, repetitive annotation is intended to disrupt the term’s complacent usage and encourage rethinking of how one manages bacteriuria. The term “urinary tract dysbiosis” may be useful for otherwise well patients with urinary tract symptoms.

“UTI” is an ill-defined, glibly overdiagnosed and overtreated “infection”. Current management ignores modern science. The associated antibiotic overuse causes serious harm to patient safety and to public health. Instead of the current-paradigm question, “Does this patient have a UTI?” the successor-paradigm question will be, “Does evidence show that antibiotic treatment is likely to benefit this patient?” Shifting the paradigm is an urgent matter.

Published on Leave a comment on Early Childhood Antibiotic Use and Food Allergies

Yikes! Another study showing effects from antibiotic use - this time a higher incidence of food allergies in children who took antibiotics in the first year of life. Especially multiple courses of antibiotics, with the strongest association among children receiving cephalosporin and sulfonamide antibiotics. Antibiotics can be life-saving, but there can also be unintended consequences.

As the researchers wrote: "Changes in the composition, richness, and abundance of microbiota that colonize the human gut during infancy has been theorized to play a role in development in atopic disease, including food allergen sensitization. " And what changes the gut microbes? Antibiotics. Other research suggests that alterations in microbes due to childhood antibiotic use may increase the risk of Crohn's disease, obesity, and asthma. From Science Daily:

Young children's antibiotic exposure associated with higher food allergy risk

Antibiotic treatment within the first year of life may wipe out more than an unwanted infection: exposure to the drugs is associated with an increase in food allergy diagnosis, new research from the University of South Carolina suggests.

Analyzing South Carolina Medicaid administrative data from 2007 to 2009, researchers from the College of Pharmacy, School of Medicine and Arnold School of Public Health identified 1,504 cases of children with food allergies and 5,995 controls without food allergies, adjusting for birth month and year, sex and race/ethnicity. Applying conditional logistic regression and adjusting for factors including birth, breastfeeding, asthma, eczema, maternal age and urban residence, the researchers found that children prescribed antibiotics within the first year of life were 1.21 times more likely to be diagnosed with food allergy than children who hadn't received an antibiotic prescription.

The association between antibiotic prescription and development of food allergy was statistically significant, and the odds of a food allergy diagnosis increased with the number of antibiotic prescriptions a child received, growing from 1.31 times greater risk with three prescriptions to 1.43 times with four prescriptions and 1.64 times with five or more prescriptions. The interdisciplinary research team, led by Bryan Love, Pharm.D., found the strongest association between children who were prescribed cephalosporin and sulfonamide antibiotics, which are broad-spectrum therapies (adjusted OR 1.50 and 1.54, respectively), compared with narrower spectrum agents such as penicillins and macrolides. .

This research builds upon previous studies finding that normal gut flora is critical for developing the body's tolerance to foreign proteins such as food. Antibiotics are known to alter the composition of gut flora, and U.S. children ages three months to three years are prescribed 2.2 antimicrobial prescriptions per year on average, according to the literature. The study's results suggest a potential link between the rise in antibiotic prescriptions for young children and the rise in diagnosis of food allergies in children.