HoldsUp

FoundMyFitness · 2022-02-08 · Rhonda Patrick (host), Eran Elinav

Dr. Eran Elinav on Microbiome Insights into Personalized Response to Diet, Obesity, and Leaky Gut

59 research-tied claims examined: 6 overstated 2 context 47 supported 4 unverified

47

Supported by research

0:02:01Eran Elinavsupportedmoderate

The timing of food intake has an independent effect on the composition and metabolic/circadian function of gut microbes across a 24-hour cycle.

"actually the timing of diet has an independent and very peculiar effect on the composition and on the function of our gut microbes. And through these time-dependent interactions, our gut microbiome can independently impact our metabolic health or our propensity to develop diseases such as obesity and type 2 diabetes." (said at 0:02:01)

Studies in both animal models and humans demonstrate that feeding timing directly drives diurnal fluctuations in gut microbial composition and functional pathways across a 24-hour cycle. Disruptions to these rhythmic feeding patterns alter microbiome diurnal oscillations and contribute to metabolic disturbances such as glucose intolerance and obesity, effects that were shown to be transferable via fecal microbiota transplantation.

  • supports: Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. (Cell 2014) · cited 1444x in the literature
    "Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation." (abstract, results, passage verified)
    pubmedfull study (doi)
0:04:04Rhonda Patrick (host)supportedhigh

Postprandial glucose response is significantly higher in the evening compared to the morning, and humans are more insulin sensitive in the morning.

"there's been quite a few studies now that have shown that people, if you give them identical foods in the morning versus the evening time and you look at postprandial glucose response, for example, you'll see that people, you know, their postprandial glucose response is much higher in the evening. People are more insulin sensitive in the morning as well." (said at 0:04:04)

Extensive controlled human trials consistently show that glucose tolerance and insulin sensitivity follow a circadian rhythm, resulting in significantly higher postprandial glucose excursions in the evening compared to the morning after consuming identical test meals or oral glucose loads.

0:05:34Eran Elinavsupportedlow

Disrupting circadian microbial rhythmicity via altered feeding patterns or jet lag promotes host susceptibility to obesity and type 2 diabetes.

"And once we disrupt the circadian microbial activity, for example by changing the patterns of our diet or by subjecting mice to jet lag behavior, the microbes go crazy and stop behaving in this orderly manner throughout the course of a day. And this directly reflects on how the host behaves in its normal circadian behavior, and we found that once we disrupt the microbes, the host is now susceptible to develop obesity and type 2 diabetes" (said at 0:05:34)

The speaker's statement accurately summarizes published experimental findings demonstrating that disrupting the diurnal oscillations of the gut microbiome—via altered feeding schedules, host molecular clock ablation, or simulated jet lag—results in dysbiosis and loss of microbial rhythmicity. In mice and human fecal transfer models, this jet-lag-induced microbial disruption led to glucose intolerance and obesity. Because these causal findings rely primarily on animal models and small-scale human fecal transplantation experiments into germ-free mice, the certainty of the evidence for broad human disease etiology is low.

0:06:10Eran Elinavsupportedmoderate

Shift workers who experience chronic sleep-wake disturbances are at a substantially higher risk of developing obesity and type 2 diabetes.

"such as shift workers that are at a substantial risk of developing obesity and type 2 diabetes." (said at 0:06:10)

Extensive meta-analyses and umbrella reviews of prospective cohort studies consistently demonstrate that shift workers—particularly night and rotating shift workers experiencing circadian and sleep disruption—have a significantly elevated risk of developing both obesity and type 2 diabetes. Meta-analyses report an approximately 30% to 40% increased relative risk of incident type 2 diabetes among shift workers compared to daytime workers, as well as significantly higher odds of overweight and obesity (odds ratio ~1.43 for fixed night shifts).

0:07:35Eran Elinavsupportedvery low

Time-restricted feeding can completely restore normal microbiome circadian rhythmicity and downstream host metabolic and immune function in jet-lagged or clock-deficient mice.

"However, if we take all of these disrupted conditions and now we time-restrict the feeding of these mice to imitate the normal eating behavior in non-disrupted mice, then we can completely restore the microbiome circadian activity and its effect on the metabolic and immune function of the host." (said at 0:07:35)

Preclinical animal research from Thaiss and colleagues demonstrated that disruption of host circadian rhythms (through molecular clock ablation such as Per1/2 deficiency or simulated jet lag) disrupts diurnal feeding patterns, leading to loss of microbiome diurnal oscillations, dysbiosis, and impaired host metabolic homeostasis. Time-restricted feeding during the normal nocturnal active phase restored microbial diurnal compositional fluctuations, biogeographical localization, metabolome rhythms, and downstream host metabolic and transcriptional oscillations in these mouse models. Because the finding is based primarily on preclinical rodent experiments, the certainty of evidence is very low.

0:15:10Eran Elinavsupportedmoderate

In African populations, seasonal changes between rainy and dry seasons cause consistent, reproducible shifts in the gut microbiome due to different crop availability.

"For example, there are studies in Africa looking into rainy or dry seasons, which are characterized by different exposures to different crops and different foods, and and you can see that this is a very consistent and very reproducible change that that is based on the changes in the in in the, um, in these seasons and and what they represent." (said at 0:15:10)

Longitudinal studies tracking traditional African populations across seasonal cycles, most notably the Hadza of Tanzania, demonstrate cyclic and reproducible reconfigurations of the gut microbiota. Distinct taxonomic groups disappear and reappear in correspondence with the dietary shifts between wet and dry seasons (such as seasonal availability of honey, berries, tubers, and game).

0:16:37Eran Elinavsupportedmoderate

Abruptly changing a diet from vegetarian to carnivore reproducibly shifts the average population gut microbiome composition to accommodate the new macronutrient profile.

"if you abruptly change the composition of the diet, um, from one type to another, for example, from a veggie to a carnivore diet, uh, um, you very reproducibly change—in an average, in a population average, you very reproducibly change the composition of the microbe into one which accommodates better the new diet." (said at 0:16:37)

A landmark controlled dietary intervention study by David et al. (2014) demonstrated that abruptly transitioning healthy human volunteers between entirely plant-based and entirely animal-based diets rapidly and reproducibly altered gut microbial community structure and gene expression. The animal-based diet increased bile-tolerant organisms (such as Alistipes and Bilophila) and shifted metabolic activity toward amino acid fermentation, while the plant-based diet enriched microbes that ferment dietary plant polysaccharides, mirroring functional differences between carnivorous and herbivorous mammals.

  • supports: Diet rapidly and reproducibly alters the human gut microbiome. (Nature 2014) · cited 10374x in the literature
    "Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation." (abstract, results, passage verified)
    pubmedfull study (doi)
0:23:10Eran Elinavsupportedmoderate

Early life exposure to antibiotics in mice and humans increases the risk of developing asthma and obesity later in life.

"And especially in mice, but also to some extent in humans, um, it was shown that, uh, early life exposure to antibiotics, for example, uh, could save lives in many cases, but the price that we may pay is an increased risk for these diseases such as asthma—these are elegant studies that were performed by my friend and colleague Brett Finlay—and to obesity in later life" (said at 0:23:10)

Experimental animal research and observational human studies support the claim. In murine models, early-life exposure to antibiotics perturbing the gut microbiome increases susceptibility to allergic asthma (Russell et al., 2012). In human prospective cohorts and systematic reviews, early postnatal antibiotic exposure is associated with increased risk and incidence of childhood asthma (Patrick et al., 2020) as well as childhood overweight and obesity (Rasmussen et al., 2018; Asgari et al., 2023), particularly with repeated courses or treatment in the first months of life.

0:25:28Eran Elinavsupportedmoderate

Autoimmune and autoinflammatory diseases are significantly less prevalent in countries with higher early-life exposure to environmental infections compared to cleaner, industrialized nations.

"supported, for example, by epidemiological um evidence of of some of the autoimmune or autoinflammatory diseases being much less prevalent in kind of, you know, quote-unquote uh dirtier countries or countries in which um um the prevalence of exposure at early life to environmental infection is higher as compared to um cleaner, quote-unquote, countries which suffer from an uh from a marked increase in in these autoimmune or other inflammatory diseases." (said at 0:25:28)

Extensive epidemiological, ecological, and migration data support the observation that autoimmune and chronic inflammatory diseases (such as type 1 diabetes, multiple sclerosis, and inflammatory bowel disease) have a markedly lower prevalence in developing nations with high early-life microbial and infectious exposure compared to highly sanitized, industrialized nations. Furthermore, migration studies demonstrate that individuals moving from countries with low disease incidence and high infectious burdens to industrialized countries adopt the higher risk of autoimmune and allergic disorders within the first generation. While observational and ecological data do not definitively prove causality in humans, the epidemiological inverse correlation is well-documented and corroborated by experimental animal models.

0:28:00Eran Elinavsupportedmoderate

Human infants are born sterile and acquire their gut microbiome postnatally from immediate surroundings and parents.

"First of all, um every child is born um sterile, to the best of our knowledge, and acquires his or her microbiome during the neonatal period from his or her immediate surrounding, which mainly consists of their parents who are very close to them." (said at 0:28:00)

The speaker's statement reflects the prevailing scientific consensus regarding the 'sterile womb hypothesis' and initial infant microbiome colonization. Although several 16S rRNA gene sequencing studies in the 2010s suggested bacterial presence in the placenta, amniotic fluid, and meconium, subsequent comprehensive re-analyses and well-controlled low-biomass metagenomic studies demonstrated that these signals were largely artifacts of reagent contamination, laboratory background DNA, or delivery exposure. Current evidence indicates that healthy human fetuses develop in a sterile environment and undergo initial, massive microbial colonization during and after birth from maternal and environmental exposures.

0:29:15Eran Elinavsupportedmoderate

A study of 500 individuals showed that only 1.9% of gut microbiome variability is explained by human genetics, while nearly 99% is explained by environmental factors.

"What we found was that most of the effect shaping our microbiome comes from the environment. Only 1.9% of the variability in the human microbiome could be explained by differences in the human genes, while close to 99% of the variability in the human microbiome was explainable by factors coming from people's environment." (said at 0:29:15)

A landmark 2018 study by Rothschild et al. in Nature examined genotype and gut microbiome data from over 1,000 healthy individuals to quantify the relative contributions of host genetics versus environmental factors. The authors found that host genetics plays a minimal role, with an average SNP-based heritability (h2_SNP) of approximately 1.9% across taxa, while environmental factors (such as shared household, diet, lifestyle, and medications) dominate inter-individual microbiome variation.

  • supports: Environment dominates over host genetics in shaping human gut microbiota. (Nature 2018) · cited 3027x in the literature
    "Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements." (abstract, results, passage verified)
    pubmedfull study (doi)
0:29:55Eran Elinavsupportedmoderate

Human height is determined almost entirely by host genetics with no microbiome contribution, whereas metabolic traits like weight, waist-to-hip ratio, and cholesterol are substantially influenced by both host genetics and the gut microbiome.

"So, for example, if you look at human height, it is not affected by the microbes whatsoever. So almost all of the explanation for differences in human height came from the human genes and not from the microbes. However, when we looked at a number of metabolic parameters such as weight, uh waist-to-hip ratio, cholesterol levels, and many other metabolic features, we found that the microbes, the microbiome, and the human genes had independent and very substantial effects on these traits." (said at 0:29:55)

A landmark 2018 study (Rothschild et al., Nature) analyzing genotype and microbiome data from 1,046 healthy individuals evaluated the relative contributions of host genetics (heritability) and gut microbiome composition (microbiability) across multiple human phenotypes. They demonstrated that while human height has high genetic heritability with virtually zero microbiome contribution, metabolic and anthropometric traits—including body mass index, waist-to-hip ratio, fasting glucose, and cholesterol measures—exhibited substantial and significant microbiability, with microbiome data significantly improving trait prediction beyond host genetics alone.

0:25:28Eran Elinavsupportedmoderate

Early-life microbiome disruption or depletion increases susceptibility to developing inflammatory bowel disease (IBD) later in life.

"They're very elegant studies by my colleague um Martin Blaser from from NYU showing um in mice and I think also in humans that uh um that that this overly uh uh uh um these distinct uh um depletion or changes on the development of the microbiome could impact on the susceptibility to develop diseases such as inflammatory bowel disease in later life." (said at 0:25:28)

Experimental animal research and human epidemiological data support the claim that early-life microbiome disruption increases susceptibility to inflammatory bowel disease (IBD) later in life. Studies from Martin Blaser's group demonstrated that a single early-life course of antibiotics in mice exacerbated subsequent dextran sodium sulfate-induced colitis and that fecal transfer of the perturbed microbiota alone conferred increased disease severity. In humans, a systematic review and meta-analysis of observational studies found childhood antibiotic exposure was associated with an increased risk of developing IBD (RR 1.42, 95% CI 1.23–1.66), including Crohn's disease (RR 1.59) and ulcerative colitis (RR 1.23).

0:01:00Rhonda Patrick (host)supportedhigh

Food intake is the primary signal that resets peripheral circadian clocks in organs such as the liver, whereas light resets the master clock in the suprachiasmatic nucleus.

"We have talked quite a bit about circadian rhythms on the podcast from, you know, the master circadian clock in our suprachiasmatic nucleus and how light resets that clock and how there's peripheral circadian clocks in other organs such as the liver, and how food intake is the major signal that resets that clock." (said at 0:01:00)

The statement accurately reflects established mammalian circadian biology. The central master pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus is primarily synchronized (entrained) by ambient light via retinal pathways. In contrast, peripheral circadian oscillators in metabolic organs such as the liver, kidney, and pancreas are not directly light-sensitive and are predominantly entrained and reset by food intake and feeding schedules.

0:33:00Eran Elinavsupportedmoderate

The PREDICT trial demonstrated that gut microbiome and host data can be used to predict an individual's triglyceride levels.

"Another group from the UK conducted a very ambitious follow-up trial similar to the Personalized Nutrition Project, which we started with, called the PREDICT trial. And in this trial, they could show something very exciting, which is that the microbiome and the host could use to predict a person's triglyceride levels." (said at 0:33:00)

The PREDICT 1 study (Personalised REsponses to DIetary Composition Trial, n = 1,002 healthy adults and twins in the UK, validated in a 100-person US cohort) demonstrated that person-specific factors—particularly the gut microbiome—substantially influenced postprandial blood triglyceride responses. Using machine-learning models incorporating gut microbiome, host characteristics, and meal composition, the investigators successfully predicted individual postprandial triglyceride responses (Pearson r = 0.47).

  • supports: Human postprandial responses to food and potential for precision nutrition. (Nature medicine 2020) · cited 903x in the literature
    "Person-specific factors, such as gut microbiome, had a greater influence (7.1% of variance) than did meal macronutrients (3.6%) for postprandial lipemia, but not for postprandial glycemia (6.0% and 15.4%, respectively); genetic variants had a modest impact on predictions (9.5% for glucose, 0.8% for triglyceride, 0.2% for C-peptide). Findings were independently validated in a US cohort (n = 100 people). We developed a machine-learning model that predicted both triglyceride (r = 0.47) and glycemic (r = 0.77) responses to food intake." (abstract, results, passage verified)
    pubmedfull study (doi)
0:36:55Eran Elinavsupportedvery low

Mice exposed to saccharin developed microbiome-driven disturbances in glycemic response that were transferable to germ-free mice via fecal microbiome transfer.

"And what we found to our very big surprise was that um mice featured a counterintuitive disturbance in their glycemic responses when they were exposed to saccharin, and this was driven by their microbiome. So, for example, when you exposed mice to to um saccharin at different doses and took the microbiome after this exposure and transferred it into germ-free mice that never saw saccharin, they developed the same disturbances um in blood sugar control as those of the donor mice." (said at 0:36:55)

A landmark 2014 animal and human study published in Nature demonstrated that mice consuming non-caloric artificial sweeteners (specifically saccharin) developed glucose intolerance driven by alterations in the gut microbiota. Transferring the fecal microbiota from saccharin-consuming mice into naive germ-free mice transferred this impaired glycemic response. Because this specific finding is based on animal experimental data, the GRADE certainty is rated as very low.

  • supports: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. (Nature 2014) · cited 2060x in the literature
    "Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS." (abstract, passage verified)
    pubmedfull study (doi)
0:39:52Eran Elinavsupportedmoderate

A preliminary small-scale study found that personalized glycemic responses to saccharin in humans occurred and were transferable to germ-free mice via microbiome transfer.

"So with the artificial sweeteners, as part of the original study, we we published a very preliminary small-scale study suggesting that personalized responses um to uh saccharin in humans do occur, and it could be even transferred upon microbiome transfers from human into humans into germ-free mice." (said at 0:39:52)

The speaker accurately describes published findings from their research group (Suez et al., 2014 in Nature, followed by a randomized controlled trial in 2022 in Cell). In the original preliminary human study, healthy volunteers consuming saccharin showed personalized glycemic responses (some developing impaired glucose tolerance while others did not). Fecal microbiota transplantation from human responders into germ-free (gnotobiotic) mice transferred the impaired glycemic phenotype, whereas transfer from non-responders did not.

  • supports: Artificial sweeteners induce glucose intolerance by altering the gut microbiota. (Nature 2014) · cited 2060x in the literature
    "These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects." (abstract, results, passage verified)
    pubmedfull study (doi)
  • supports: Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolera… (Cell 2022) · cited 394x in the literature
    "Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations" (abstract, results and conclusions, passage verified)
    pubmedfull study (doi)
0:46:20Eran Elinavsupportedvery low

In mouse models of recurrent obesity, mice subjected to cycles of obesogenic and low-fat diets regain progressively more weight across cycles compared to never-obese mice.

"And what we could see was exactly the same phenomenon that is observed in humans: from cycle to cycle, mice seemed to regain more and more weight, even when they started from the exact same weight as never-obese mice and were exposed to the same exact diet." (said at 0:46:20)

In published mouse models of recurrent obesity (yo-yo dieting), mice subjected to cycling between high-fat and normal chow diets exhibit accelerated and excessive weight regain upon re-exposure to obesogenic feed compared to primary weight gain in never-obese controls starting at the same baseline weight. Because this evidence is derived entirely from animal models, the GRADE certainty is very low.

0:47:05Eran Elinavsupportedvery low

Following successful dieting in mice, hormonal, endocrine, and metabolic parameters normalize, but the gut microbiome persistently retains an altered configuration similar to that during obesity.

"And it seems that everything seemed to normalize after a successful diet—all the hormonal and the endocrine and the metabolic features that we could measure totally normalized after a successful diet, other than the gut microbiome. When we measured the gut microbiome, it seemed to be persistently disturbed, as though the mice were never dieted. It had a configuration which was very similar to the one that we observed during obesity." (said at 0:47:05)

A 2016 mouse study published in Nature demonstrated that after diet-induced weight loss in obese mice, physiological and metabolic markers normalized, but the gut microbiome retained an altered composition ("microbiome memory") resembling the obese state for months post-dieting. This persistent dysbiosis promoted accelerated weight regain upon re-exposure to a high-fat diet. Because this evidence is derived exclusively from preclinical rodent models, the overall GRADE certainty is very low.

0:47:40Eran Elinavsupportedvery low

Transferring the post-dieting microbiome from previously obese mice into germ-free mice induces obesity and type 2 diabetes upon re-exposure to an obesogenic diet.

"And when we took this um microbiome that never normalized after a successful diet and transferred it into germ-free mice, these mice developed obesity and type 2 diabetes, meaning that this post-dieting microbiome stored a metabolic memory of past obesity that predisposed the mice to an exaggerated weight regain the next time they were exposed to an obesogenic diet." (said at 0:47:40)

A 2016 study led by the speaker's research group (Thaiss et al., Nature) demonstrated that mice subjected to cycles of obesity and successful dieting retained an altered gut microbiome signature. When this post-dieting microbiota was transferred into germ-free mice, recipient mice exhibited accelerated weight regain and metabolic perturbations upon re-exposure to a high-fat diet compared to controls receiving microbiota from naive lean mice. Because this finding is based entirely on preclinical mouse models, the GRADE certainty is very low regarding translation to humans.

0:48:15Eran Elinavsupportedvery low

The post-dieting gut microbiome drives exaggerated weight regain by expanding bacteria that degrade dietary isoflavonoids, preventing them from signaling adipose cells to release heat and store less fat.

"And when we probed even deeper into this memory microbiome, we found that it induced this trait of exaggerated weight regain by altering its ability to degrade dietary compounds which are called isoflavonoids. Normally, we found that isoflavonoids from diet are degraded by the microbiome to compounds which swim into adipose cells and signaling and signal to them to um to release more heat and store less fat when we are exposed to an obesogenic diet. But when these compounds were missing after a successful diet, the adipose cells, the fat cells, were no longer given the signal to release heat and not to store fat, and now they were storing more fat and making the mice more obese as compared to non-yo-yo obesity mice." (said at 0:48:15)

The speaker accurately describes the mechanism identified in their laboratory's mouse model of recurrent post-dieting obesity (yo-yo dieting). In this study (Thaiss et al., 2016), weight cycling in mice left a persistent intestinal microbiome alteration that accelerated the degradation and depletion of dietary flavonoids (such as apigenin and naringenin). This loss of flavonoid signaling led to reduced brown adipose tissue thermogenesis (energy expenditure), driving faster weight regain upon re-exposure to a high-fat diet. Because this mechanism was demonstrated exclusively in preclinical mouse experiments, GRADE certainty for human application is very low.

0:51:15Eran Elinavsupportedvery low

Resupplementing post-dieting mice with missing flavonoid metabolites or resetting their microbiome via fecal microbial transplantation prevents exaggerated weight regain.

"And indeed, at least in mice, what we've found was that if we intervened by resupplementing our mice with these now missing metabolites, we could avoid or treat exaggerated weight regain and the obesity that it induces. A different approach that we've used in mice and seemed to be highly effective is the replacement of this bad memory microbiome with a microbiome that had the ability to generate the right compounds. And by fecal microbial transplantation, at least in mice, we could reset the mice to not develop this yo-yo obesity phenotype." (said at 0:51:15)

In a 2016 mouse study published in Nature, researchers demonstrated that following diet-induced weight loss, an altered gut microbiome signature persisted and drove accelerated weight regain. This post-dieting microbiome led to diminished flavonoid levels (such as apigenin and naringenin) and impaired energy expenditure. Resupplementing mice with these depleted flavonoids (a 'post-biotic' intervention) or transferring a naive/control microbiome via fecal microbiota transplantation mitigated or prevented exaggerated secondary weight regain upon high-fat diet re-exposure. Because the findings are currently limited to preclinical animal models, certainty is very low.

0:56:30Eran Elinavsupportedmoderate

Around 50% of all small molecules (metabolites) found in the peripheral blood of animals and humans originate from or are modulated by the gut microbiome.

"In fact, we and others have measured the small molecule repertoire in peripheral blood of both animals and humans, and it seems that around 50% of all small molecules that are found within our peripheral blood may originate in one way or another or be modulated in one way or another by our gut microbes." (said at 0:56:30)

Metabolomic comparisons between germ-free and conventionally colonized mammalian models demonstrate that the gut microbiota exerts a massive influence on the circulating metabolome. Seminal untargeted metabolomics profiling (Wikoff et al., 2009) demonstrated that hundreds of circulating plasma metabolite features were unique to conventionally colonized animals or altered in level, with subsequent studies confirming that a large fraction (often estimated up to ~30-50% or more of detected small-molecule features) in mammalian blood is derived from, modified by, or dependent upon commensal microbial metabolism (such as indoles, secondary bile acids, phenyl derivatives, and short-chain fatty acids). The speaker's statement accurately summarizes findings from mammalian comparative metabolomics literature.

0:57:18Rhonda Patrick (host)supportedhigh

Short-chain fatty acids such as butyrate, propionate, and acetate act as signaling molecules that modulate the immune system by influencing regulatory T cell (Treg) activity and production.

"I think most people that listen or watch our podcast are familiar with some of the beneficial metabolites that are produced, like these short-chain fatty acids like butyrate or propionate, acetate, but and their effects on modulating the immune system. And I think there's been just overwhelming evidence at this point that there's a role in these short-chain fatty acids for, you know, playing signaling molecule roles where they affect Treg regulatory cell activity and/or production, for example." (said at 0:57:18)

Substantial basic and translational research confirms that short-chain fatty acids (SCFAs)—predominantly butyrate, propionate, and acetate—function as signaling molecules that regulate immune responses. Mechanistically, SCFAs promote the differentiation, expansion, and suppressive activity of regulatory T cells (Tregs) through G-protein-coupled receptor (GPCR) activation (such as GPR43/FFAR2 and GPR109A) and inhibition of histone deacetylases (HDACs), which enhances Foxp3 gene expression.

0:58:22Eran Elinavsupportedhigh

The intestinal barrier separating the gut microbiome and intestinal lumen from the internal body consists of a single layer of intestinal epithelial cells.

"and the trillions of microbes that are in the intestinal lumen and are, you know, separated from our sterile self by only a single layer of intestinal epithelial cells." (said at 0:58:22)

The human intestinal epithelium is an established anatomical structure consisting of a simple (single-layer) columnar epithelium. This single layer of intestinal epithelial cells, linked by tight junctions and coated by mucus, forms the primary physical barrier separating luminal contents—including trillions of commensal microorganisms—from the underlying lamina propria, immune compartments, and internal circulation.

1:02:26Eran Elinavsupportedhigh

The gut epithelial barrier is composed of cells connected by tightly regulated junctions that can be influenced by food molecules and microbial molecules.

"and it is composed of the lining cells of the gut, the epithelial cells of the gut, which are characterized by very specific connections to one another which are tightly regulated. And these tightly regulated connections between the cells could be influenced by molecules that come from food, they could be influenced by molecules that come from the microbes, and once this regulation is disrupted, then leaky gut occurs." (said at 1:02:26)

The speaker's description accurately reflects established physiological principles regarding the intestinal barrier. The gut mucosal layer is composed of epithelial cells bound together by specialized protein complexes called tight junctions (including claudins, occludins, and zonula occludens). These tight junctions tightly regulate paracellular permeability and are responsive to both microbial signals (such as short-chain fatty acids, indoles, and bile acid derivatives) and dietary components (such as specific lipids, carbohydrates, and phytochemicals). Disruption of these regulated junctional complexes increases epithelial permeability, leading to the condition clinically described as intestinal hyperpermeability or leaky gut.

1:02:58Eran Elinavsupportedmoderate

The generation and preservation of the protective gut mucus layer is regulated by bacterial and environmental factors, including medications, toxins, and food components.

"And it is increasingly shown that the generation and the preservation of this protective mucus is also regulated by a number of bacterial and environmental factors such as medications, toxins, and food components." (said at 1:02:58)

The speaker accurately states that the generation, maintenance, and regulation of the intestinal mucus layer are influenced by gut microbiota and environmental factors, including dietary components, ingested toxins (such as alcohol), and pharmacological agents. Published reviews demonstrate that interactions between the gut microbiota, dietary components, and environmental exposures play a key role in modulating mucin secretion by goblet cells and maintaining intestinal mucosal integrity.

1:04:34Eran Elinavsupportedhigh

Gliadin is a major protein in bread that triggers an immune cascade resulting in increased intestinal permeability in genetically susceptible individuals with celiac disease.

"For example, gliadin is the major protein that is a part of bread, what makes our dough sticky and what makes our bread tasty. And in individuals that suffer from a genetic susceptibility to develop immune reactivity to this protein, then a cascade of immune reaction occurs that leads, among many other changes, to a leaky bowel or to a leaky gut, which contributes to a disease state in the celiac patients." (said at 1:04:34)

Extensive pathophysiological and clinical research confirms that gliadin (a major protein component of wheat gluten) triggers an immune-mediated cascade in genetically susceptible individuals (principally carrying HLA-DQ2 or HLA-DQ8 haplotypes), leading to zonulin upregulation, tight junction disassembly, increased intestinal permeability ('leaky gut'), and enteropathy characteristic of celiac disease.

1:08:40Eran Elinavsupportedmoderate

In a study testing 11 over-the-counter probiotic strains in humans and mice, the indigenous microbiome prevented the probiotics from colonizing the gut in approximately half of human participants.

"when we studied probiotics—we studied 11 different types of commonly prescribed over-the-counter probiotics, and we studied them both in mice and in humans in probably the most invasive microbiome study performed to date—we found that in around half the people that we've tested, when they take these probiotic bacteria and supplement them into their diet, the probiotics are met with a very hostile indigenous microbiome which does not let them colonize our gut even temporarily." (said at 1:08:40)

The speaker accurately describes their 2018 study published in Cell (Zmora et al., 2018). In that trial, researchers administered an 11-strain commercial probiotic preparation to mice and human volunteers, using invasive upper endoscopy and colonoscopy to directly sample mucosal-associated gut microbiota rather than relying solely on stool. In colonized mice and in human participants, probiotics encountered significant indigenous mucosal colonization resistance; human participants exhibited distinct person-specific mucosal colonization patterns, bifurcating into 'permissive' and 'resistant' phenotypes where baseline microbiome and host features prevented mucosal colonization.

  • supports: Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with … (Cell 2018) · cited 1690x in the literature
    "A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool." (abstract, results, passage verified)
    pubmedfull study (doi)
1:09:20Eran Elinavsupportedmoderate

In individuals whose guts resisted probiotic colonization, probiotic consumption caused no measurable changes in gut mucosal responsiveness.

"And by sampling these volunteer participants by invasive colonoscopy and endoscopy at different stages of probiotic exposure, we could find that in individuals that consume probiotics but are not able to colonize these exogenous bugs along their gut, we could see absolutely no impact on the gut responsiveness to these exogenous probiotics." (said at 1:09:20)

A clinical trial evaluating human gastrointestinal mucosal responses via upper endoscopies and colonoscopies during empiric probiotic supplementation demonstrated personalized mucosal colonization resistance. In participants displaying mucosal colonization resistance, the probiotic strains were shed in stool without establishing mucosal residence, resulting in an absence of measurable changes in the mucosal microbiome community structure and host mucosal transcriptome.

1:09:55Eran Elinavsupportedmoderate

In individuals where supplemental probiotics colonized the gut, significant impacts were observed on gut mucosal responsiveness.

"However, in the other half of the individuals, the microbiome was much more welcoming, and when they were eating the probiotics, the probiotics at least temporarily were able to colonize along their guts. And in these individuals, we saw that these exogenous microbes indeed had quite significant impacts on our measurements of human responsiveness, or at least in the gut." (said at 1:09:55)

A clinical trial investigating human mucosal colonization by an 11-strain empiric probiotic mix found that humans display person-specific mucosal colonization patterns (distinguishing permissive colonizers from resistant individuals). In permissive individuals where mucosal colonization occurred, probiotic supplementation exerted significant, individualized impacts on mucosal microbial community structure and host gut transcriptome (mucosal gene expression responsiveness).

1:12:40Eran Elinavsupportedmoderate

Administering probiotics following antibiotic exposure persistently inhibits the natural recolonization and reconstitution of the indigenous gut microbiome.

"But now these probiotics were very persistently inhibiting the return of the indigenous microbiome after antibiotic exposure was no longer present. In other words, by giving probiotics together with antibiotics, we may be protecting some individuals from the adverse effects associated with antibiotic treatment, but the price that we may pay is the creation of a chronic disturbance in the composition of our gut microbiome, with the probiotics very aggressively refusing to leave the neighborhood and colonizing the once-diverse gut and not letting the microbiome repopulate and recolonize." (said at 1:12:40)

A landmark clinical trial evaluating post-antibiotic gut mucosal microbiome reconstitution in humans and mice demonstrated that multi-strain probiotic administration following broad-spectrum antibiotic perturbation markedly delayed and persistently impaired the recovery and reconstitution of the indigenous mucosal and stool microbiome compared to spontaneous recovery. In contrast, autologous fecal microbiome transplantation led to rapid recovery. The study also identified that soluble factors secreted by probiotic strains (such as Lactobacillus) directly contributed to the inhibition of indigenous gut bacteria.

1:17:48Eran Elinavsupportedhigh

Stool sampling does not accurately reflect whether probiotics colonize the gastrointestinal mucosa, as shed bacteria accumulate in stool regardless of colonization.

"And and we are the first to study this colonization pattern not in stool, which which is where most of the previous studies have looked into probiotics. We found that this stool is is very problematic in assessing colonization because even in people who do not colonize at all with probiotics, you know, they end up accumulating in stool because that's the natural way where they go. So you need to really sample inside the gut in order to understand whether a person colonizes or not." (said at 1:17:48)

A clinical trial evaluating human gut mucosal colonization during probiotic consumption demonstrated that probiotic strains were detectable in stool across individuals regardless of whether mucosal colonization actually occurred. Invasive sampling of the human gastrointestinal tract revealed person-, region-, and strain-specific mucosal colonization resistance patterns that could not be predicted or distinguished by examining probiotic presence in stool samples.

1:22:21Eran Elinavsupportedhigh

Bacteriophages are viruses that specifically infect and attack bacteria and do not infect humans, mammals, or eukaryotic cells.

"So bacteriophages are intriguing viruses that, in contrast to the viruses that we all, you know, suffer from these days, are viruses that do not infect humans and they do not infect any mammals or any eukaryotic cells. These are viruses that only infect bacteria and only attack bacteria." (said at 1:22:21)

Bacteriophages are defined in microbiological consensus and published literature as viruses that specifically infect and replicate within bacteria. They possess precise host specificity targeting bacterial surface receptors and do not naturally infect humans, mammals, or other eukaryotic cells, which forms the fundamental biological basis for bacteriophage therapy safety.

1:29:10Eran Elinavsupportedhigh

The human body harbors more than 3 million bacterial genes in addition to approximately 20,000 human genes.

"you know, in a matter of a decade and a half, we've discovered that our human body, in addition to the 20-something-thousand genes that are encoded in our human cells, also contain 3 million and more bacterial genes that we didn't appreciate, that we didn't know anything about." (said at 1:29:10)

Metagenomic sequencing of the human microbiome established a reference catalogue of approximately 3.3 million non-redundant microbial genes (over 99% of which are bacterial), representing approximately 150 times the ~20,000–25,000 protein-coding genes encoded in the human genome.

  • supports: A human gut microbial gene catalogue established by metagenomic sequencing. (Nature 2010) · cited 11824x in the literature
    "Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. ... Over 99% of the genes are bacterial" (abstract, passage verified)
    pubmedfull study (doi)
1:31:40Rhonda Patrick (host)supportedmoderate

TMAO is a gut-derived compound associated with atherosclerosis and heart disease that is synthesized from dietary precursors including L-carnitine in red meat and choline in eggs.

"And there's one compound that I've I've been following for a while and I continue to follow, and it's a compound that is associated with atherosclerosis and heart disease—it's TMAO. And it's produced from precursors like L-carnitine or even choline, which are found in red meat and eggs, respectively." (said at 1:31:40)

The speaker's statement accurately reflects established biomedical evidence regarding trimethylamine N-oxide (TMAO). TMAO is generated through the metabolism of dietary precursors—primarily choline (abundant in eggs) and L-carnitine (abundant in red meat)—by intestinal microbiota into trimethylamine (TMA), which is subsequently oxidized by hepatic flavin-containing monooxygenases into TMAO. Numerous prospective cohort studies, mechanistic animal models, and clinical reviews consistently demonstrate an association between elevated plasma TMAO levels, atherosclerosis, and increased risk of major adverse cardiovascular disease events.

1:11:15Eran Elinavsupportedhigh

Certain bacteria in the microbiome secrete antimicrobial peptides that function as natural antibiotics to inhibit competing bacterial species.

"Another potential set of interactions are mediated by the secretion of what we call antimicrobial peptides, which are these types of natural antibiotics which some microbes are able to secrete, which inhibit others." (said at 1:11:15)

A well-established mechanism of microbial antagonism in the human microbiome is the secretion of ribosomally synthesized antimicrobial peptides known as bacteriocins. Genomic analyses and in vitro studies confirm that widespread bacterial taxa within the human gut (including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria) produce these natural antimicrobial peptides to target, inhibit, or kill closely related strains and competing pathogenic bacterial species.

1:19:50Rhonda Patrick (host)supportedmoderate

Clinical and animal studies have reported therapeutic benefits of high-dose probiotic formulations (such as VSL#3 or Visbiome at 400 to 800 billion CFUs) for colitis and irritable bowel syndrome.

"Many of the studies at the time they were the bacteria was—the brand was called VSL#3. And and then it was like re- another—the formulation was like done again, and it was called Visbiome. But many of the publications, clinical studies, you know, including as well as animal studies, but there have been benefits, for example, on like colitis or irritable bowel syndrome with taking either 400 or 800, you know, colony-forming units, so like, you know, 800 billion" (said at 1:19:50)

Multiple randomized controlled trials and meta-analyses have reported therapeutic benefits of the high-potency probiotic formulation originally marketed as VSL#3 (later produced under the name Visbiome with the original De Simone formulation). In mild-to-moderate ulcerative colitis, meta-analyses and multicenter clinical trials have demonstrated that high doses of this formulation significantly increase clinical response and remission rates compared to placebo. In irritable bowel syndrome (IBS), individual randomized trials in pediatric and adult cohorts have reported reductions in abdominal pain, bloating, and symptom relief, though meta-analyses note that the overall evidence base across IBS subtypes is smaller and shows varying effect sizes.

1:22:45Eran Elinavsupportedhigh

CRISPR evolved naturally as a bacterial defense mechanism against bacteriophage viruses.

"It's an intriguing arms race which led to some groundbreaking discoveries such as CRISPR, which is the, you know, one of these defense mechanisms which has been now massively exploited by science in order to genome-edit, for example, genes of interest." (said at 1:22:45)

CRISPR-Cas systems evolved in bacteria and archaea as adaptive immune systems that protect prokaryotic cells against invading foreign genetic material, predominantly bacteriophages (viruses) and plasmids. This naturally occurring anti-phage defense mechanism relies on incorporating fragments of viral DNA into the host genome to recognize and cleave matching sequences during subsequent infections, and it has since been adapted widely as a tool for targeted genome editing.

1:34:08Eran Elinavsupportedhigh

Dietary compounds including choline and carnitine are converted by gut microbes into TMA, which is then metabolized by the host liver into TMAO.

"we're talking about a connection between dietary compounds such as choline and carnitine, which are digested by the microbes into a compound called TMA, which then influxes into the host and is further converted by the host, by the liver of the host, into TMAO." (said at 1:34:08)

The described meta-organismal metabolic pathway is well-established. Dietary precursors containing quaternary amines, including choline, phosphatidylcholine, and L-carnitine, are cleaved by gut microbial enzymes (such as choline TMA-lyase and carnitine oxygenase) to form trimethylamine (TMA). TMA is absorbed across the intestinal epithelium into portal circulation and transported to the liver, where it is oxidized to trimethylamine N-oxide (TMAO) primarily by host hepatic flavin-containing monooxygenases (predominantly FMO3).

1:34:08Eran Elinavsupportedmoderate

Circulating TMAO can impact macrophages that contribute to atherosclerotic plaque formation.

"And this TMAO swims into the circulation, where in some instances it could impact macrophages that form plaques that are responsible for atherosclerosis and its potentially devastating health effects: heart disease, brain disease, kidney disease, and and more." (said at 1:34:08)

Published preclinical and observational research demonstrates that circulating trimethylamine N-oxide (TMAO) promotes atherosclerosis by directly modulating macrophage biology. In experimental models, TMAO upregulates macrophage scavenger receptors (such as CD36 and SR-A1), increases oxidized LDL uptake, impairs cholesterol efflux, and promotes macrophage foam cell formation and inflammatory cytokine production within vascular plaques.

1:36:11Eran Elinavsupportedvery low

Interactions between the microbiome and host generate compounds that drive the obesity that develops after smoking cessation.

"we've recently published another study focusing on a peculiar type of obesity that develops after cessation of cigarette smoking. And to make a long story short, we found a similar cooperation between the microbiome and the host in generating compounds that could drive this obesity phenomenon after smoking cessation." (said at 1:36:11)

A 2021 study by the speaker's group published in Nature demonstrated that gut microbiota changes driven by cigarette smoke exposure and cessation promote smoking-cessation-induced weight gain in mouse models. The mechanism involved concerted host and microbiome metabolic cooperation, specifically shunting dietary choline to dimethylglycine (driving increased energy harvest) alongside the depletion of N-acetylglycine. Because the primary causal mechanism was established in animal models with only preliminary observational human cohort data, the certainty of evidence for human clinical outcomes remains very low.

1:38:14Eran Elinavsupportedmoderate

Maintaining healthy sleep patterns and avoiding erratic sleep-wake behavior affects the microbiome and host regulation of weight and glucose metabolism.

"maintaining healthy sleep patterns and avoiding as much as possible erratic sleep-wake behavior has very profound effects on on our measurement of the microbiome and how it impacts our regulation of of weight and and the glucose or sugar metabolism or the avoidance of type 2 diabetes, for example." (said at 1:38:14)

The speaker's claim is supported. Published preclinical and clinical research demonstrates that circadian and sleep disruptions (such as erratic sleep-wake schedules, shift work, and sleep fragmentation) disrupt the diurnal rhythmicity and taxonomic composition of the gut microbiota. Mechanistic studies show that microbiota alterations resulting from circadian desynchrony impair short-chain fatty acid fermentation, disrupt host peripheral clock gene expression, promote weight gain, and induce insulin resistance and glucose intolerance.

1:39:14Eran Elinavsupportedlow

Cigarette-related chemicals reach the systemic circulation, penetrate the gut, and alter the composition and function of the microbiome.

"when we measure what it does to the microbiome, we were intrigued to find that many cigarette-related chemicals not only reach the systemic circulation, but they actually penetrate the gut and they impact the microbiome towards a disturbed composition and function." (said at 1:39:14)

Published experimental research in animal models, supported by preliminary human observational data, confirms that inhaled cigarette smoke-derived chemicals enter the systemic circulation, penetrate the gastrointestinal tract, and drive compositional and functional changes (dysbiosis) in the gut microbiome. A landmark 2021 study showed that an intestinal influx of cigarette-smoke-related metabolites directly alters gut microbial composition and function, modulating host metabolism and energy harvest.

1:40:17Eran Elinavsupportedmoderate

Dietary meal timing, including the timing of dinner the previous night, serves as a predictive feature for postprandial glycemic response algorithms.

"in our personalized nutrition machine learning algorithms, which are used to predict a person's dietary responses in a very accurate manner, the timing of our diet and even the timing of our meal last night are part of the features that are used by this unbiased algorithm in order to form its very accurate predictions." (said at 1:40:17)

Machine-learning models developed for personalized nutrition to predict postprandial glycemic responses incorporate contextual dietary factors, including meal timing, time elapsed since the previous meal, and previous nutritional intake, alongside microbiome, anthropometric, and clinical blood parameters. In a landmark cohort study of 800 individuals tracking continuous glucose across tens of thousands of meals (validated in an independent cohort and a randomized dietary intervention), these multidimensional features accurately predicted individualized postprandial glycemic responses to real-world meals.

1:41:20Eran Elinavsupportedmoderate

In a 2015 study of 1,000 individuals, machine learning algorithms integrating continuous glucose monitoring and microbiome data accurately predicted personalized glycemic responses to food.

"we analyzed the data from a thousand individuals in Israel that kindly gave us a week of their life, and we measured and collected an unprecedented amount of microbiome and host-related data, including a smartphone app that was used in this study and a continuous glucose measurement that generated very accurate measurements of sugar responses to food in a week of follow-up. And then very sophisticated machine learning and AI technologies were used to generate predictive algorithms for each individual that are able to accurately predict a person's sugar responses to any given food." (said at 1:41:20)

In a 2015 landmark study published in Cell by Zeevi et al. (the research group of Eran Segal and Eran Elinav), researchers continuously monitored glucose levels for a week in an 800-person discovery cohort (measuring responses to 46,898 meals) and a 100-person validation cohort in Israel. They developed a machine-learning algorithm incorporating gut microbiota, blood parameters, anthropometrics, and dietary habits to accurately predict personalized postprandial glycemic responses to meals.

  • supports: Personalized Nutrition by Prediction of Glycemic Responses. (Cell 2015) · cited 2901x in the literature
    "Here, we continuously monitored week-long glucose levels in an 800-person cohort, measured responses to 46,898 meals, and found high variability in the response to identical meals, suggesting that universal dietary recommendations may have limited utility. We devised a machine-learning algorithm that integrates blood parameters, dietary habits, anthropometrics, physical activity, and gut microbiota measured in this cohort and showed that it accurately predicts personalized postprandial glycemic response to real-life meals. We validated these predictions in an independent 100-person cohort." (abstract, results, passage verified)
    pubmedfull study (doi)
1:41:20Eran Elinavsupportedmoderate

A randomized clinical trial demonstrated that a personalized, data-driven diet outperformed the American Diabetes Association-recommended diet in controlling blood glucose in pre-diabetic individuals.

"tested by us in different contexts, including recently in a long-term randomized human trial which compared this data-driven personalized approach to the gold standard American Diabetes Association-recommended diet. And we've quite convincingly showed that this personalized, science-driven approach was outperforming the current one-size-fits-all diet in a large group of pre-diabetic individuals" (said at 1:41:20)

A 2021 randomized controlled trial (Ben-Yacov et al., published in Diabetes Care) evaluated 225 adults with prediabetes assigned to either a personalized postprandial-targeting (PPT) diet driven by machine-learning algorithms or a standard Mediterranean diet (an ADA-recommended dietary pattern). Over a 6-month intervention and subsequent 6-month follow-up, the personalized diet led to significantly greater reductions in daily time spent with glucose >140 mg/dL and greater reductions in HbA1c compared to the Mediterranean diet.

  • supports: Personalized Postprandial Glucose Response-Targeting Diet Versus Mediterranean Diet for Gl… (Diabetes care 2021) · cited 150x in the literature
    "Both interventions reduced the daily time with glucose levels >140 mg/dL (7.8 mmol/L) and HbA 1c levels, but reductions were significantly greater in PPT compared with MED. The mean 6-month change in "time above 140" was -0.3 ± 0.8 h/day and -1.3 ± 1.5 h/day for MED and PPT, respectively (95% CI between-group difference -1.29 to -0.66, P < 0.001). The mean 6-month change in HbA 1c was -0.08 ± 0.19% (-0.9 ± 2.1 mmol/mol) and -0.16 ± 0.24% (-1.7 ± 2.6 mmol/mol) for MED and PPT, respectively (95% CI between-group difference -0.14 to -0.02, P = 0.007)." (abstract, results, passage verified)
    pubmedfull study (doi)

Unverified means no publication matching the claim was located; it does not prove the claim false. Spotted an error? See the corrections policy - disputes from the people quoted are prioritized.