Gut Bacteria Might be an Indicator of Colon Cancer Risk

A study published today in the journal Cell Host & Microbe reported that the increased presence of certain bacteria in a gut biome indicates a greater likelihood that colon polyps will become cancerous.

In his research, William DePaolo, associate professor at the University of Washington School of Medicine, tracked 40 patients who had undergone routine colonoscopies and had biopsies taken near the polyps to identify bacteria present at relatively higher levels compared with those of patients who were polyp-free. All the patients were between the ages 50 and 75, and 60% were women.

“The rising incidence of colorectal cancer is a major health concern, but little is known about the composition and role of microbiota associated with precancerous polyps,” the study states.

DePaolo’s research team found that a common bacteria, non-enterotoxigenic Bacteroides fragilis, was elevated in the mucosal biopsies of patients with polyps.

The research also found distinct microbial signatures distinguishing patients with polyps from those without polyps, and established a correlation between the amount of B. fragilis in the samples and the inflammation of small polyps.

Upon closer examination, DePaolo found that the B. fragilis from patients with polyps differed in its ability to induce inflammation compared to the B. fragilis from polyp-free individuals.

“The whole idea is that most people look at advanced colorectal cancer and think of the microbiome, but it’s hard to determine if the microbiome has changed and when it changed,” DePaolo said. “So we took an earlier look at the disease and asked when might the microbiome may be pushing a polyp toward cancer.”

Also, when people think of the microbiome and its role in disease, they often think of compositional changes where a potentially dangerous bacteria takes over, he added.

“What our data suggests is that, in order to survive within an environment where metabolic and inflammatory changes are occurring, a normally healthy gut and related bacteria may adapt in such a way that causes it to contribute to the inflammation rather than suppress it,” DePaolo explained.

Only 5% of the polyps in the colon actually turn out to be cancerous, he said. He said polyps seem to develop in the same areas of the colon repeatedly – and he theorized that in fact new screenings for colon cancer could look for key bacteria inhabiting the gut – and the amounts of this particular strain of B. fragilis – before pre-cancerous polyps even develop.

Colorectal cancer is the third leading cause of cancer in the United States, and its incidence is rising among younger adults. If a screening were available to test the microbes, before a polyp even appears, it could be a key factor to drive these rates down, DePaulo suggested.

The next step, he said, is to expand the study to 200 patients to determine whether a fecal sample might be used as a surrogate for the mucosal biopsy.

Source: University of Washington

Gut Bacteria and Flavonoid-rich Foods Are Linked and Improve Blood Pressure Levels

Flavonoid-rich foods, including berries, apples, pears and wine, appear to have a positive effect on blood pressure levels, an association that is partially explained by characteristics of the gut microbiome, according to new research published today in Hypertension, an American Heart Association journal.

“Our gut microbiome plays a key role in metabolizing flavonoids to enhance their cardioprotective effects, and this study provides evidence to suggest these blood pressure-lowering effects are achievable with simple changes to the daily diet,” said lead investigator of the study Aedín Cassidy, Ph.D., chair and professor in nutrition and preventive medicine at the Institute for Global Food Security at Queen’s University in Belfast, Northern Ireland.

Flavonoids are compounds found naturally in fruits, vegetables and plant-based foods such as tea, chocolate and wine, and have been shown in previous research to offer a variety of health benefits to the body. Flavonoids are broken down by the body’s gut microbiome—the bacteria found in the digestive tract. Recent studies found a link between gut microbiota, the microorganisms in the human digestive tract, and cardiovascular disease (CVD), which is the leading cause of death worldwide. Gut microbiota is highly variable between individuals, and there are reported differences in gut microbial compositions among people with and without CVD.

With increased research suggesting flavonoids may reduce heart disease risk, this study assessed the role of the gut microbiome on the process. Researchers examined the association between eating flavonoid-rich foods with blood pressure and gut microbiome diversity. The study also investigated how much variance within the gut microbiome could explain the association between intake of flavonoid-rich foods and blood pressure.

A group of 904 adults between the ages of 25 and 82, 57% men from Germany’s PopGen biobank were recruited for this study. (The PopGen biobank includes participants from a network of seven biobanks in Northern Germany.) Researchers evaluated the participants’ food intake, gut microbiome and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.

Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods. Flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.

Gut microbiome for participants was assessed by fecal bacterial DNA extracted from stool samples. After an overnight fast, participants’ blood pressure levels were measured three times in three-minute intervals after an initial five-minute rest period. Researchers also collected participants’ lifestyle information, including sex, age, smoking status, medication use and physical activity, as well as family history of coronary artery disease, the number of daily calories and fiber consumed, and each participant’s height and weight was measured to calculate BMI (body mass index).

The analysis of regular flavonoid intake with gut microbiome and blood pressure levels found:

  • Study participants who had the highest intake of flavonoid-rich foods, including berries, red wine, apples and pears, had lower systolic blood pressure levels, as well as greater diversity in their gut microbiome than the participants who consumed the lowest levels of flavonoid-rich foods.
  • Up to 15.2% of the association between flavonoid-rich foods and systolic blood pressure could be explained by the diversity found in participants’ gut microbiome.
  • Eating 1.6 servings of berries per day (one serving equals 80 grams, or 1 cup) was associated with an average reduction in systolic blood pressure levels of 4.1 mm Hg, and about 12% of the association was explained by gut microbiome factors.
  • Drinking 2.8 glasses (125 ml of wine per glass) of red wine a week was associated with an average of 3.7 mm Hg lower systolic blood pressure level, of which 15% could be explained by the gut microbiome.

“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Cassidy. “A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”

While this study suggests potential benefits to consuming red wine, the American Heart Association suggests that if you don’t drink alcohol already, you shouldn’t start. If you do drink, talk with your doctor about the benefits and risks of consuming alcohol in moderation. According to a statement on dietary health by the American Heart Association, alcohol intake can be a component of a healthy diet if consumed in moderation (no more than one alcoholic drink per day for women and 2 alcohol drinks per day for men) and only by nonpregnant women and adults when there is no risk to existing health conditions, medication-alcohol interaction, or personal safety and work situations.

The authors note that participants for the study were from the general population, and the participants were unaware of the hypothesis. However, residual or unmeasured confounding factors (such as other health conditions or genetics) can lead to bias, thus these findings cannot prove a direct cause and effect, although the researchers did conduct a detailed adjustment in their analyses for a wide range of diet and lifestyle factors. The authors noted the focus of this study was on specific foods rich in flavonoids, not all food and beverages with flavonoids.

Source: American Heart Association

Research Identifies Link Between Gut Microbes and Stroke

New findings from Cleveland Clinic researchers show for the first time that the gut microbiome impacts stroke severity and functional impairment following stroke. The results, published in Cell Host & Microbe, lay the groundwork for potential new interventions to help treat or prevent stroke.

The research was led by Weifei Zhu, Ph.D., and Stanley Hazen, M.D., Ph.D., of Cleveland Clinic’s Lerner Research Institute. The study builds on more than a decade of research spearheaded by Dr. Hazen and his team related to the gut microbiome’s role in cardiovascular health and disease, including the adverse effects of TMAO (trimethylamine N-oxide) – a byproduct produced when gut bacteria digest certain nutrients abundant in red meat and other animal products.

“In this study we found that dietary choline and TMAO produced greater stroke size and severity, and poorer outcomes in animal models,” said Dr. Hazen, chair of the Department of Cardiovascular & Metabolic Sciences and director of Cleveland Clinic’s Center for Microbiome & Human Health. “Remarkably, simply transplanting gut microbes capable of making TMAO was enough to cause a profound change in stroke severity.”

Previously, Dr. Hazen and his team discovered that elevated TMAO levels can lead to the development of cardiovascular disease. In clinical studies involving thousands of patients, they have shown that blood levels of TMAO predict future risk of heart attack, stroke and death -findings that have been replicated around the world. Earlier studies, also led by Drs. Zhu and Hazen, were the first to show a link between TMAO and enhanced risk for blood clotting.

“This new study expands on these findings, and for the first time provides proof that gut microbes in general – and through TMAO specifically – can directly impact stroke severity or post-stroke functional impairment,” said Dr. Hazen.

The researchers compared brain damage in preclinical stroke models between those with elevated or reduced TMAO levels. Over time, those with higher levels of TMAO had more extensive brain damage and a greater degree of motor and cognitive functional deficits following stroke. The researchers also found that dietary changes that alter TMAO levels, such as eating less red meat and eggs, impacted stroke severity.

“Functionality after a stroke – which occurs when blood flow to the brain is blocked – is a major concern for patients,” said Dr. Hazen, who is also co-section head of Preventive Cardiology & Cardiac Rehabilitation in Cleveland Clinic’s Miller Heart, Vascular & Thoracic Institute. “To understand if choline and TMAO affect post-stroke functionality, in addition to stroke severity, we compared performance on various tasks pre-stroke, and then both in the short- and long-term following stroke.”

The team found that a gut microbe enzyme critical to TMAO production called CutC drove heightened stroke severity and worsened outcomes.

According to Dr. Zhu, targeting this gut microbe enzyme may be a promising approach to prevent stroke. “When we genetically silenced the gut microbe gene that encodes CutC, stroke severity significantly diminished,” she said. “Ongoing research is exploring this treatment approach, as well as the potential for dietary interventions to help reduce TMAO levels and stroke risk, since both a Western diet and a diet rich in red meat are known to elevate TMAO levels. Switching to plant-based protein sources helps to lower TMAO.”

Source: Cleveland Clinic

Study Reveals Connection Between Gut Bacteria and Vitamin D Levels

Heather Buschman wrote . . . . . . . . .

Our gut microbiomes — the many bacteria, viruses and other microbes living in our digestive tracts — play important roles in our health and risk for disease in ways that are only beginning to be recognized.

University of California San Diego researchers and collaborators recently demonstrated in older men that the makeup of a person’s gut microbiome is linked to their levels of active vitamin D, a hormone important for bone health and immunity.

The study, published November 26, 2020 in Nature Communications, also revealed a new understanding of vitamin D and how it’s typically measured.

Vitamin D can take several different forms, but standard blood tests detect only one, an inactive precursor that can be stored by the body. To use vitamin D, the body must metabolize the precursor into an active form.

“We were surprised to find that microbiome diversity — the variety of bacteria types in a person’s gut — was closely associated with active vitamin D, but not the precursor form,” said senior author Deborah Kado, MD, director of the Osteoporosis Clinic at UC San Diego Health. “Greater gut microbiome diversity is thought to be associated with better health in general.”

Kado led the study for the National Institute on Aging-funded Osteoporotic Fractures in Men (MrOS) Study Research Group, a large, multi-site effort that started in 2000. She teamed up with Rob Knight, PhD, professor and director of the Center for Microbiome Innovation at UC San Diego, and co-first authors Robert L. Thomas, MD, PhD, fellow in the Division of Endocrinology at UC San Diego School of Medicine, and Serene Lingjing Jiang, graduate student in the Biostatistics Program at Herbert Wertheim School of Public Health and Human Longevity Sciences.

Multiple studies have suggested that people with low vitamin D levels are at higher risk for cancer, heart disease, worse COVID-19 infections and other diseases. Yet the largest randomized clinical trial to date, with more than 25,000 adults, concluded that taking vitamin D supplements has no effect on health outcomes, including heart disease, cancer or even bone health.

“Our study suggests that might be because these studies measured only the precursor form of vitamin D, rather than active hormone,” said Kado, who is also professor at UC San Diego School of Medicine and Herbert Wertheim School of Public Health. “Measures of vitamin D formation and breakdown may be better indicators of underlying health issues, and who might best respond to vitamin D supplementation.”

The team analyzed stool and blood samples contributed by 567 men participating in MrOS. The participants live in six cities around the United States, their mean age was 84 and most reported being in good or excellent health. The researchers used a technique called 16s rRNA sequencing to identify and quantify the types of bacteria in each stool sample based on unique genetic identifiers. They used a method known as LC-MSMS to quantify vitamin D metabolites (the precursor, active hormone and the breakdown product) in each participant’s blood serum.

In addition to discovering a link between active vitamin D and overall microbiome diversity, the researchers also noted that 12 particular types of bacteria appeared more often in the gut microbiomes of men with lots of active vitamin D. Most of those 12 bacteria produce butyrate, a beneficial fatty acid that helps maintain gut lining health.

“Gut microbiomes are really complex and vary a lot from person to person,” Jiang said. “When we do find associations, they aren’t usually as distinct as we found here.”

Because they live in different regions of the U.S., the men in the study are exposed to differing amounts of sunlight, a source of vitamin D. As expected, men who lived in San Diego, California got the most sun, and they also had the most precursor form of vitamin D.

But the team unexpectedly found no correlations between where men lived and their levels of active vitamin D hormone.

“It seems like it doesn’t matter how much vitamin D you get through sunlight or supplementation, nor how much your body can store,” Kado said. “It matters how well your body is able to metabolize that into active vitamin D, and maybe that’s what clinical trials need to measure in order to get a more accurate picture of the vitamin’s role in health.”

“We often find in medicine that more is not necessarily better,” Thomas added. “So in this case, maybe it’s not how much vitamin D you supplement with, but how you encourage your body to use it.”

Kado pointed out that the study relied on a single snapshot in time of the microbes and vitamin D found in participants’ blood and stool, and those factors can fluctuate over time depending on a person’s environment, diet, sleep habits, medications and more. According to the team, more studies are needed to better understand the part bacteria play in vitamin D metabolism, and to determine whether intervening at the microbiome level could be used to augment current treatments to improve bone and possibly other health outcomes.

Source: UC San Diego

Cholesterol Lowering Drugs – Statins – are Linked to Improved Gut Bacteria Composition in Obese People

The human gut microbiota consists of trillions of bacteria, fungi and virus constituting an inner chemical factory producing a multitude of microbial compounds affecting immunity, neurobiology and metabolism of the human host.

It has for long been known that imbalances in the composition of gut microbes link with a variety of chronic human disorders spanning from obesity, diabetes inflammatory bowel diseases to depression, schizophrenia, autism and Parkinson. In addition, it is known that unhealthy dieting and use of some medications, for instance stomach acid neutralizers, the so-called proton pump inhibitors, are associated with a further disruption of the microbial communities of the gut.

Now, in a new paper in the scientific journal Nature, The MetaCardis investigators explore gut bacteria in almost 900 individuals from Denmark, France and Germany.

The intestinal microbiota in obese individuals had previously been shown to differ from those in lean subjects with a poor bacterial diversity, a relative depletion of health promoting bacteria and the remaining bacteria dominated by an inflammatory tone.

In their Nature article, the researches now define a cluster of bacteria called Bact2 enterotype, which is found in 4% of lean and overweight people but in 18% of obese individuals who did not use statin drugs, a group of cholesterol lowering medications.

However, in other obese study participants who were treated with statins, the prevalence of the unhealthy Bact2 enterotype was significantly lower (6%) than in their non-treated counterparts (18%) – comparable to levels observed in non-obese participants (4%). The same trend was validated in a Flemish study sample of about 2000 participants.

Statins are commonly prescribed to reduce risk of developing cardiovascular diseases like myocardial infarction and stroke. It is estimated that more than 200 million people worldwide are prescribed statins. Besides their cholesterol-lowering effects, statins also tend to appease patients’ systemic inflammation levels which in part may be related to a disrupted gut microbiota.

The results suggest that statins could potentially modulate the disrupted gut microbiota and linked inflammation in obesity. Previous experiments in rodents have shown an impact of statins on bacterial growth, which might benefit non-inflammatory bacteria and underlie the anti-inflammatory effects of statin therapy. Obviously, clinically controlled human trials are needed to address whether statins mediate some of their anti-inflammatory effect via an improvement of the Bact2 enterotype of an aberrant gut microbiota.

Source: University of Copenhagen