Do gut bacteria contribute to ethnic health disparities?

Do gut bacteria contribute to ethnic health disparities?

The bacteria living in our guts play a major role in health, and some studies have found an association between ethnicity and the makeup of these microbial communities. So will doctors of the future prescribe ethnicity-specific probiotics?

We share our bodies with a vast community of bacteria. According to the latest estimate, the human body contains about 38 trillion bacterial cells and approximately 30 trillion human cells.

Scientists know that this community of gut bacteria, or microbiota, plays a role in healthy digestion and immune function. This has spurred sales of probiotics that manufacturers promote as boosting populations of “friendly” bacteria. Many of these products’ supposed health benefits remain unproven, however.

Studies have nonetheless found strong associations between particular species of gut bacteria and a range of diseases, including obesity, inflammatory bowel disease (IBD), and colorectal cancer.

Fecal transplants from healthy individuals can restore populations of beneficial gut bacteria and displace disease-causing species. For example, they have shown promise at suppressing Clostridium difficile, a bacterium that can cause life-threatening diarrhea and inflammation of the colon.

However, in June 2019, the Food and Drug Administration (FDA) issued a safety warning about the risk of developing bacterial infections due to transplanting fecal microbiota.

There is also some evidence that fecal transplants can treat a range of other disorders associated with disturbances in the microbiota, including IBD and obesity, among other diseases.

Ethnic connection

Each person’s gut microbiota is unique, but shared factors and characteristics, such as diet, age, sex, lifestyle, and genetics, influence it.

A study by scientists at Vanderbilt University in Nashville, TN, published in the journal PLoS Biology in 2018, found that a person’s ethnicity is a better predictor of the microbial community in their gut than other variables, such as body mass index (BMI), age, and sex.

Other research suggests that gut microbiota has associations with health disparities between ethnic and racial groups, such as increased incidence of colorectal cancer in African Americans and increased incidence of obesity and type 2 diabetes in Mexican Americans.

This raises the intriguing possibility that doctors could adjust a person’s bacterial communities — perhaps using fecal transplants or probiotics — according to their ethnicity or race.

The Vanderbilt University scientists studied data on the gut microbiota of almost 1,700 people from the American Gut Project and Human Microbiome Project, identifying 12 bacterial groupings, or taxa, that consistently varied between ethnic groups.

“If you look at common factors associated with gut microbiome differences, such as gender, weight, or age, you find many inconsistencies in the types of gut bacteria present,” said biologist Seth Bordenstein, senior author of the study.

“But when we compare differences by patients’ self-declared ethnicities, we find stable and consistent features of bacteria present in the gut.”

Precision probiotics

Bordenstein directs the Vanderbilt Microbiome Initiative, a collaboration between five Vanderbilt schools and colleges investigating the human microbiome: the collective genetics of our microbiota.

The ultimate objective of the initiative is to develop probiotic treatments as a form of precision medicine tailored to the genetics, metabolism, and microbiome of particular individuals or groups.

“You may buy probiotics over the counter at a drugstore, but those are unlikely to affect your microbiome in a substantial way,” said Bordenstein. “They often are at too low a dose, and they may not even be viable bacteria. Moreover, one size may not fit all.”

“But with more of this kind of research, we can hone in on the relevant differences and doses of bacteria that may reverse illness or prevent it from developing in the first place.”

The majority of the bacteria identified in the study are partly heritable. Heritability is a measure of the extent to which differences between people’s genes account for differences in their characteristics, or traits — in this case, their gut microbiota.

The research at Vanderbilt suggests that self-identified ethnicity, which is partly determined by the genes a person inherited from their parents, plays a role in the type of bacteria that live in their guts. This, in turn, may help to shape their effect on health.

Nature and nurture

But human beings are much more than the product of their genes. A complex interplay of genetic and environmental influences determines who we are, and the relationship between ethnicity, health, and gut microbiota is no exception.

The ethnic group with which people identify encompasses not just genetics but also a wide range of cultural factors, including the food they have eaten since childhood. Scientists know that these factors influence not only our gut microbiota but also our metabolic health.

A study in 2015, for example, found evidence that the gut microbiota of Mexican Americans has associations with their high risk of obesity and type 2 diabetes.

But it is important to note that other environmental and behavioral factors also contribute to this increased risk, including diet and levels of physical activity.

The picture gets even more complicated with the addition of the socioeconomic influences on health that unequally affect different ethnic or racial groups. These include income, educational opportunities, and access to healthcare.

A question of geography

So how much of a role does ethnicity really play in the makeup of our microbiota, and by extension in the health disparities that exist between different ethnic groups?

The study by Bordenstein and his colleagues encompassed the whole of the United States. The many regional differences introduced many confounding variables into the analysis.

Researchers at the University of Amsterdam in the Netherlands limited these variables by focusing on a relatively small geographical region.

They studied 2,084 individuals living in the same city who identified as belonging to one of six ethnic groups: Moroccan, Turkish, Ghanaian, African Surinamese, South Asian Surinamese, and Dutch.

In 2018, they reported in Nature Medicine that ethnicity was the strongest determinant of differences in the subjects’ gut microbiota. Its influence was more significant than alcohol consumption, age, smoking, diet, and education levels, for example.

Nonetheless, ethnicity’s sole contribution to differences between individuals was only 2.5–3%, after accounting for other variables, such as diet.

Highly heritable bacteria

The researchers identified some subtle differences. They identified that Dutch people harbored relatively high concentrations of the Christensenellaceae group of bacteria. In contrast, the South-Asian Surinamese people had relatively low levels.

The researchers describe Christensenellaceae as highly heritable bacteria that have associations with greater diversity in the overall gut microbiota. Scientists have linked their presence to several health benefits, including lower BMI and less risk of IBD.

However, scientists remain unsure of how ethnicity underlies its influence on the microbiome.

In conclusion, the authors write:

“Ethnicity comprises many different aspects — genetics, cultural habits, migration (for example, socioeconomic status, health care and antibiotics use, early-life environment) — which may all contribute to shaping the gut microbiota … Although the influence of genetics is likely low (2–8% heritability) compared to environmental factors, especially diet, it may participate in building diverse profiles of gut microbiota that would be further refined by the environment.”

According to this view, the shared genetic inheritance of a particular ethnic group initiates subtle differences in their gut bacteria. Shared environmental influences then amplify these differences.

Sharing a home

Another study appears to contradict this view, however. It suggests that our current environment has a more profound influence on our gut microbiota than our genes.

A 2018 study published in Nature found that the microbiomes of genetically unrelated individuals who share a household have significant similarities, whereas blood relatives who have never lived together do not.

The researchers at the Weizmann Institute of Science in Rehovot in Israel analyzed the microbiomes of 1,046 healthy individuals of six different ethnicities: Ashkenazi, North African, Middle Eastern, Sephardi, Yemenite, and mixed ancestry.

They found that while their genetic ancestry did not have a statistically significant effect on their microbiomes, more than 20% of its variability had links to other factors that the scientists took into consideration, including diet and lifestyle.

According to this line of evidence, ethnicity by itself has no more than a subtle effect on our microbiota, whereas factors such as diet and the people with whom we live play much more prominent roles.

This would seem to argue against doctors choosing probiotic treatments based on a person’s ethnicity because it would not be precise. Genuine precision medicine would entail individualizing the treatment to a person’s individual genetic, microbiotic, and lifestyle characteristics, rather than using their ethnicity as a convenient proxy.

Controversial history

Race-based medicine has a controversial recent history in the U.S.

In 2005, the FDA approved the first race-based medicine — a drug combination called BiDil for treating heart failure in Black patients. The patent on BiDil expired in 2020.

At the time, there was some evidence that Black people responded better to this treatment than the standard therapy.

Critics of the decision argued that its one-size-fits-all approach meant that some Black patients might receive a treatment that didn’t work for them, while non-Black patients might not have access to a potentially effective treatment.

Jonathan Kahn, a law professor at Northeastern University School of Law in Boston, MA, and the bioethicist Pamela Sankar at the University of Pennsylvania have claimed that the decision to develop BiDil as a race-based medicine had more to do with securing a patent than precision medicine.

One final consideration in the question of whether ethnic probiotics might work is genetic variability.

Genome research has found that there is more genetic variation within human populations than between them. This calls into question the whole notion of race or ethnicity as a useful biological construct.

It suggests that geographical ancestry may not be a reliable proxy for a person’s genetic makeup, let alone all the other factors that contribute to their health, such as diet, exercise, and the kinds of bacteria living inside them.

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