Frequently Asked Questions
Both Intermittent Fasting And Calorie Restriction May Benefit The Gut
Intermittent fasting and calorie reduction are both effective methods of supporting all-important microbiome diversity. A new study from the University of Colorado's medical school highlights how changes in the gut microbiome, brought about through dietary interventions, can influence gene regulation and overall health.
Both intermittent fasting and calorie-reduction diets positively affect the microbiome, the community of bacteria living in a person's digestive system and throughout the body.
Participants in the study, all of whom had either overweight or obesity, were either instructed to fast for 3 non-consecutive days each week for a year or, alternately, to reduce their regular caloric intake by around 34% over the same period.
An earlier analysis found that the diversity of gut bacteria in individuals' microbiomes was significantly improved, even at only 3 months into the year-long study. Improvements were seen for both groups — those who fasted and those who focused on reducing their daily calorie intake.
The analysis suggested that a person can improve the diversity of their microbiome and potentially their overall health using the weight-reduction strategy of their choice.
The new study reinforces the idea that changes in gut bacteria occur during weight loss. The researchers observed several associations between the abundance of microbes associated with metabolism and obesity and DNA methylation, a process by which gene regulation is altered, potentially impacting our health.
The study appears in Nutrients.
Inside the human body are roughly 100 trillion symbiotic microbial cells. Most of these are bacteria, and most live in the upper and lower intestine. Our understanding of these tiny organisms is still somewhat in its infancy. However, it is clear that they are influential actors in our health.
Gastroenterologist Dr. Rudolph Bedford, who was not involved in the study, explained: "The gut microbiome mediates so many different things. It mediates any type of inflammatory process going on within your body."
Inflammation in the body has been implicated in many medical issues, from cancer to diabetes, dementia, and heart disease.
In addition, the microbes in the microbiome influence other processes as well, including appetite and obesity.
Dr. Bedford said:
"You want a very diverse microbiome because the more diversity you have, the better variety of function in various aspects of your body you will have. You want a very diverse microbiome in order to decrease and regulate all the mechanisms within your body."
Research bears out the value of a diverse microbiome. Dietician Kristin Kirkpatrick — also not involved in the study — addded that "microbial diversity has been associated with a better microbiome."
"Studies have shown that healthy individuals often have a more diverse gut microbiota. We also see in the data that the greater the beneficial microbes, the greater the change of beneficial health outcomes," said Kirkpatrick.
The researchers, following their earlier analysis, had commented that the mechanism could be the benefits seen with changes in metabolism, weight loss, cardiometabolic factors, or even improvements in dietary patterns associated with the two arms of intervention.
Dr. Bedford suggested a simpler reason. "The microbiome is working full-time," he said. So when you fast or eat less, "[y]ou're resting it, allowing it to repopulate, just like sleep. That's certainly one of the theories as to why you're improving [diversity] with intermittent fasting, things of that sort."
Nevertheless, Kirkpatrick cautioned that "[t]here is no one size fits all approach to diet, so each individual diet needs to be assessed with a health practitioner."
In addition, she advised that "[p]regnant women, [those who are] breastfeeding, or someone struggling with a chronic condition should speak with their doctor or dietitian prior to altering their dietary pattern."
The dietitian also expressed concern that fasting diets and calorie reduction could cause further harm to people with a history of disordered eating.
"Individuals with a history of eating disorders or current disordered eating should also not consider fasting or low-calorie approaches," said Kirkpatrick.
Fasting can be performed in a variety of ways. While participants in the study fasted 3 days a week, fasting can also be done for a few hours, or for multiple days in a row.
Dr. Bedford noted that "[t]he problem with fasting is that unfortunately, as human beings, we fast, let's say for 12 to 16 hours, we go home, and then we overeat."
He cautioned that fasting is not a good idea for people with diabetes, since the prolonged lack of food causes fluctuations of blood sugar and insulin levels.
Previous research has found that calorie reduction, if it is too extreme, can cause an increase in pathogenic bacteria in the gut, and may otherwise disrupt the microbiome.
Dr. Bedford did not question the findings of this research. However, he suggested that extreme calorie reduction is an unlikely practice.
"I think it's more theoretical: You're telling a normal person to starve themselves. It takes an enormous amount of discipline to do that. So, unless you're capable of going on a hunger strike, I don't see that as much of an issue. In 30 years, I've never seen it," he told us.
"In an industrialized society," said Dr. Bedford, "there are probably in our food supply no more than five or six different animals. And in terms of plants, again, a very limited number of plant products that we also consume."
"You throw in all the antibiotics that we're using to deal with our animals, and all the pesticides we're using on the plants. Those are things that tend to limit the diversity of your microbiome because you are what you eat and so are the bacteria," he continued.
"As a gastroenterologist, we're all seeing younger and younger people with colon cancers, and it's a phenomenon that's actually at epidemic proportions in first-world countries," said Dr. Bedford.
He noted the existence of so-called blue zones, regions around the world in which people live exceptionally long lives. "There's one in Loba Linda in the state of California, believe it or not," he said.
There is a reason, he said, why people live longer in these areas: "It's because it's mostly a plant-based diet, a diversity of plant-based diets. And it changes the microbiome for the better, and therefore the less disease, fewer issues, and fewer problems."
Novel 'fast, Tenacious' Molecule Can KO Drug-resistant Superbugs
Decades of work has seemingly paid off with scientists developing a potent new synthetic molecule that swiftly knocked out 285 strains of bacteria it was tested on, setting it up as a valuable ally in our fight against a looming superbug infection crisis.
It's not the first modern breakthrough in synthetic antibiotics, with a lot of research now laser-focused on finding new ways to tackle often deadly bacteria that's increasingly circumventing our longstanding traditional drugs.
This new molecule works by disrupting the bacterium's ability to form an outer lipid layer, both killing the pathogen and rendering it unable to multiply – a stress response that can be triggered by antibiotics resistance, making infections much more difficult to treat.
"If you disrupt the synthesis of the bacterial outer membrane, the bacteria cannot survive without it," said lead investigator Pei Zhou, a professor of biochemistry in the Duke School of Medicine. "Our compound is very good and very potent."
The compound, LPC-233, messed with lipid formation in every gram-negative bacterium it was tested on. Among the 285 bacterial strains it was pitted against, including some with high antibiotics resistance, it killed them all efficiently and quickly.
"LPC-233 can reduce bacterial viability by 100,000-fold within four hours," Zhou said.
While all tests have so far been on mice models, it was successful when administered orally, intravenously and injected into the abdomen. LPC-233 was also able to target what would have normally been a fatal dose of multidrug-resistant bacteria, perhaps the hardest 'superbug' to defeat with current medical intervention.
While Zhou has been working on this breakthrough for years, credit should also go to his late colleague, Christian Raetz, former Duke biochemistry chair, highlighting how few science discoveries happen overnight. Incidentally, LPC-233 got its name because the team had tried, failed and improved on the molecule some 232 times before landing on what they were after.
"He spent his entire career working on this pathway," Zhou said. "Dr Raetz proposed a conceptual blueprint for this pathway in the 1980s, and it took him over two decades to identify all of the players."
LPC-233 targets the LpxC enzyme, which is on the "Raetz pathway." Earlier developments targeting LpxC resulted in cardiovascular toxicity in human trials.
"We realized that we could tweak the compound to make it better," Zhou said of his work, initially with Raetz and then alongside Duke chemistry professor Eric Toone. "It fits in the right way to inhibit formation of the lipid. We're jamming the system."
What's more, after the compound binds to LpxC, it changes its shape to become an even more stable complex. Importantly, this gives it the stability to outlive the lifespan of bacteria.
"We think that contributes to the potency, as it has a semi-permanent effect on the enzyme," he said. "Even after the unbound drug is metabolized by the body, the enzyme is still inhibited due to the extremely slow inhibitor dissociation process."
In December 2022, the World Health Organization sounded the alarm on how quickly antibiotic-resistant bacteria are adapting to current drugs and how critically important it is to develop new ways to fight these bugs.
The scientists have now patented LPC-233 and some other compounds and have established a startup to develop the drug. That company, ValenBio Therapeutics, is now planning phase 1 clinical trials to test LPC-233 safety and efficacy in humans.
The research was published in the journal Science Translational Medicine.
Source: Duke University
Antibiotic Resistance, Mutation Rates And MRSA
As worrisome as MRSA is, it is just the tip of the iceberg, so to speak. In fact, there are a number of far more threatening drug-resistant bacteria in existence, such as Pseudomonas aeruginosa. P. Aeruginosa poses a greater threat because it has certain biological features that make it more readily resistant to antibiotics than MRSA. For example, P. Aeruginosa has a highly impermeable outer membrane, whereas MRSA does not. This outer membrane makes it more difficult for antibiotic chemical compounds to actually get inside the bacterial cell so that they can inflict damage. Moreover, once the antibiotic compounds are inside it, P. Aeruginosa has what are known as efflux pumps, which can very quickly pump foreign compounds like antibiotics back out of the cell before they have a chance to do damage. MRSA does not have efflux pumps. Because of these biological features, P. Aeruginosa infections either quickly evolve multidrug resistance or are drug-resistant from the start. Unlike with MRSA, however, the likelihood of picking up a P. Aeruginosa infection from a doorknob in a school building is practically nil. P. Aeruginosa infections occur mostly among hospital patients—at least for now.
In both the hospital and the community, antibiotic resistance has emerged as a major public health problem. In fact, some scientists consider it the most important public health problem of the twenty-first century. The problem exists not just because bacterial mutation rates lead to a rapid accumulation of mutations (including drug-resistant mutations), but also because of the selective pressures that antibiotics impose. If a drug-resistant phenotype were to evolve and there were no antibiotic present, then that phenotype would fare no better than any other bacterial phenotype. In other words, it wouldn't flourish, and it might even die out. It is only when antibiotics are used that drug-resistant phenotypes have a selective advantage and survive.
Of course, not all mutations confer resistance, and most probably have nothing at all to do with resistance. That said, bacterial populations with especially high mutation rates (so-called "hypermutable" strains) often have higher antibiotic resistance rates. For example, in a study of cystic fibrosis (CF) patients infected with P. Aeruginosa (which is a major cause of sickness and death among CF patients), where more than a third of all CF patients had hypermutable P. Aeruginosa infections, the hypermutable populations had higher resistance rates than isolates with "normal" mutation rates (Oliver et al., 2000). Plus, there are other ways that bacteria evolve resistance, in addition to spontaneous nucleotide base mutations. For instance, bacteria can acquire resistance genes through conjugation (i.E., from plasmid DNA) and from recombination with other bacterial DNA following transformation.
The emergence and spread of antibiotic resistance has become such an important public health problem that many federal and state public health agencies now distribute educational posters to encourage "good hygiene" practices—practices that prevent the spread of antibiotic-resistant bacteria from one person to another and help keep those mutant S. Aureus bacteria off doorknobs. Maybe you have seen one of these posters in a school hallway, in a locker room, or in a public bathroom, imploring you to wash your hands with soap and water to help prevent disease.
To make MRSA matters even worse, in 2002, health care workers reported the first cases of vancomycin-resistant MRSA. In other words, even "last-resort" vancomycin doesn't always work. Therein lies the crisis: People are dying from "simple" bacterial infections, all because of a very low mutation rate.
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