Microbes Adapt to Their New Environment Along with Their Immigrant Hosts

Microbes Adapt to Their New Environment Along with Their Immigrant Hosts

A recent article published by Dan Knights’ group at the University of Minnesota and reported in the journal Cell reports that gut microbial composition and diversity changed within months in immigrants from rural Asian environments to the US. The authors’ key findings were:

  • Immigration to the US from rural regions in Asia is associated with loss of gut microbial species, diversity and loss of bacterial enzymes associated with plant fiber degradation
  • Bacteroides strains displaced fiber-digesting Prevotella strains according to time spent in the USA
  • Loss of diversity increased with obesity and was compounded across generations

“People began to lose their native microbes almost immediately after arriving in the U.S.,” Knights said when interviewed by The Washington Post. “The loss of diversity was quite pronounced: Just coming to the USA, just living in the USA, was associated with a loss of about 15 percent of microbiome diversity.” Interestingly, the children of immigrants had another 5 to 10 percent loss of diversity.

Knights and his colleagues examined the relative abundance and diversity of gut microbes and their gene content in stool samples from more than 500 immigrant women from rural areas in Asia, the Hmong and Karen people. To get a snapshot before and after arrival in the US, researchers also took microbiome samples from 19 Karen women before their departure and after their arrival. The scientists compared all of these microbiomes with those of 36 European Americans born in the United States.

The dominant species in the gut of immigrants changed from strains of a group of bacteria called Prevotella to a group called Bacteroides. The genus Prevotella belongs to the taxa Bacteroidites which together with the taxa Firmicutes makes up the majority of gut microbes in the human GI tract.

Similar differences in gut microbial taxa between the remnants of hunter gatherer populations in Africa (Hadza) and South America (Yanomami), and populations living in industrialized countries, in particular in North America, Europe and Australia have previously been described (Smits et al. Science 357, 2017; De Filippo, PNAS 2010). Industrialized populations have microbiotas that are dominated by Bacterioidites, whereas traditional populations across the African, Asian, and South American continents, which include a range of lifestyles from rural agriculturalists to hunter gatherers, have microbiotas that are in part distinguished by their abundances of Prevotella taxa, just like in the Knight’s study (Smits et al. Science).

Village Africa Burkina Faso
For example, In a study of gut bacteria of children in Burkina Faso, a region in Africa, Prevotella made up 53% of the gut bacteria, but were absent in age-matched European children. Studies also indicate that long-term diet is strongly associated with the gut microbiome composition—those who eat plenty of protein and animal fats typical of Western diet have predominantly Bacteroides bacteria, while for those who consume more complex carbohydrates, especially fiber, the Prevotella species dominate. Prevotella species produce enzymes that digest fiber containing foods which are more common in Asia than the United States.

While these gut microbial differences between people living in different parts of the world seemed initially like a stable regional trait, two recent studies, including the one by Knight strongly suggest that they are influenced by dietary and other lifestyle factors. Do the gut microbiota which are programmed during the first 3 years of life adapt to different diets and demands on the most effective metabolic machinery?

To answer this question, Justin Sonnenburg and his group looked at possible relationships between seasonal variations of dietary habits and the composition and functional capacity of the gut microbiota. The Hadza’s living in the Rift Valley in East Africa have two distinct seasons: a wet season from November to April and a dry season from May to October. Even though consumption of fiber-rich tubers and plants occurs year-round, berry foraging and honey consumption are more frequent during the wet season, while hunting is most successful during the dry season, resulting consumption in the consumption of lean meet from wild game. The period of higher meat consumption was associated with an increase in Bacteroidetes species in the gut. The same class of microbes declined again during the wet season to a state with significant similarity to those of industrialized microbiota. The taxa that are driven to undetectable levels in the Hadza microbiota during the wet season correspond to taxa that are rare or absent, regardless of season, in industrialized populations. However, in contrast to the changes seen in industrialized populations in gut microbial diversity and richness, as well as expression of distinct patterns of digestive enzymes, the Hadza’s microbiome always returned to its full diversity during the dry season.

It would have been fascinating to know if the gut microbial reductions in gut microbial diversity and fiber degrading species seen in Knights’ immigrants would have been reversible upon returning to their land and dietary habits of origin, as it happens in the Hadzas during the different seasons, or if these changes were permanent as they are in industrialized countries.

Did the rapid changes in gut microbial composition and function have any consequences for the health of the immigrants? It is generally assumed that as microbial diversity decreases, the risk of diseases such as obesity, diabetes and metabolic syndrome increases, even though causality between microbial changes and human diseases remains to be established. Indeed, Knights’ group observed that obesity rates among many of the study immigrants increased up to sixfold. Those who became obese also lost an additional 10 percent of their diversity.

As the observed changes in the diet of the immigrants were slower than the observed rapid changes in the gut microbiome of immigrants suggest that factors other than North American food must have played a role, including stress associated with the resettlement and adapting to a new environment, water purity, exposure to medications, in particular antibiotics and other lifestyle factors.

Comments:

  • Several studies demonstrate variations in gut microbial diversity and relative abundance of microbial taxa. These variations can occur in a cyclical, seasonal pattern in some populations, or can occur when a population moves from one country and traditional dietary habits to one with high fat, high sugar and low fiber diet.
  • In industrialized countries, an increase in microbial diversity and abundance only occurs within a certain bandwidth, but generally does not reach the levels seen in traditional societies.
  • Even though differences in dietary intake appear to be playing a prominent role in this microbiome variations, factors other than diet could be responsible, in particular stress, physical activity, hygiene and purity of the drinking water.
  • However, to date, no causal relationship between gut microbial changes and obesity or other diseases has been identified.
Can the Iceman Tell Us Something About the Healthiest Diet?

Can the Iceman Tell Us Something About the Healthiest Diet?

The “Iceman” or “Ötzi” refers to an individual whose mummy was found about 10 years ago in the receding glaciers of the Ötztal Alps a mountain range in the central Alps between Austria and Italy. His well preserved body has been stored in a cooling chamber of the Archeology Museum in Bolzano, Italy, and is probably the most thoroughly investigated individual from the Neolithic period.

Can the stomach contents of this individual reveal something about the preferred diet of people transitioning from a hunter gatherer to an agrarian lifestyle, and the associated health benefits?

To answer this question, investigators have examined the stomach contents of this 5,300-year old European glacier mummy who according to the latest forensic studies was killed by an arrow shortly after enjoying his last meal. The study revealed that the Iceman had a remarkably high proportion of fat in his diet, supplemented with fresh or dried wild meat and ancient grains. An earlier study had demonstrated that the gut microbial composition of the Iceman was more similar to microbiomes of agrarian societies (and of primates), suggesting a predominantly plant based diet with an occasional treat of wild game.

Do we have any evidence for the health benefits of this ancient diet? The investigators were surprised of the large amount of animal fat found in the person’s stomach. The investigators asked: “Did he load up on fatty meat to meat the caloric needs of roaming in the extreme alpine environment in which he lived and where he was found at 3,210m above sea level?” On the other hand, the intake of animal adipose tissue fat has a strong correlation with increased risk of coronary artery disease. There was evidence on computer tomographic scans of the Iceman that he had major calcifications of his major blood vessels consisting with advanced atherosclerotic disease state, a surprising finding in an individual who likely got regular vigorous workouts climbing up and down the mountains in his backyard. He was in his 40s, the average life expectancy of people of his time, half of our current life expectancy.

Obviously, the study only provides a snapshot of dietary habits of this time, and tells us little about the average intake of different types of food and the relative proportion of carbs, protein and fat. However, in view of the presence of grains and carbohydrates in his stomach and the composition of his gut microbiome, the Iceman was certainly not adhering to a strict paleo diet.

Even though many other factors are obviously involved, it is surprising that when comparing cardiovascular health and longevity, our often maligned North American diet combined with our sedentary lifestyle is associated with much better health outcomes than those of our Neolithic ancestors, something to consider when claiming health benefits from ancient diets high in meat and animal fats.

Maixner F et al. The Iceman’s last meal consisted of fat, wild meat and cereals. Current Biology 28:2348-55, 2018

Lessons Learned from the Gut Microbiome of Hibernating Brown Bears

Lessons Learned from the Gut Microbiome of Hibernating Brown Bears

Obesity and compromised metabolic health are often thought to be closely linked. However, a study by Fredrik Baeckhed’s group at the University of Gothenburg suggests that this is not necessarily the case – at least in brown bears! (1)

By studying body weight and the gut microbiota in brown bears both during the summer and during the winter period – when these animals go into a 6 months hibernation period – they identified major differences in the diversity and relative abundances of certain gut microbiota. During the summer the bears overeat and dramatically gain body weight, while during the prolonged fasting period in winter they lose all the excess weight. The most fascinating aspect of this study was that despite their “summer obesity” the bears did not develop the negative metabolic changes including insulin resistance and diabetes known as metabolic syndrome, a metabolic dysregulation which has shown a dramatic increase in North America and other developed countries.

Looking for a possible role of the gut microbiome in these seasonal metabolic changes, the investigators looked at the bears’ gut microbes and metabolites. Surprisingly, during hibernation there was a reduction in diversity and reduced levels of certain taxa, in particular Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Transfer of the stool of bears obtained during different seasons into germ free mice (mice without their own gut microbiome) mimicked some of the metabolic findings of the bears, clearly implicating a role of the microbiome in the seasonal metabolic variations.

The three microbial taxa that showed seasonal variations in the bears make up the majority of the human gut microbiota, and changes in their relative abundance in the gut have previously been shown by Ruth Ley and coworkers in obese subjects. (2) In their study, they found that the relative abundance of Bacteroidetes increases while that of Firmicutes decreases as obese individuals lose weight on either a fat- or a carbohydrate-restricted low-calorie diet. The increase in Bacteroidetes was significantly correlated to weight loss but not to total caloric intake. In a study by Peter Turnbaugh and coworkers, the investigators showed that when ‘obese microbiota’ were transplanted into the gut of mice without their own microbiota (so called germ free mice) they showed a significantly greater increase in total body fat than mice colonized with the ‘lean microbiota’. Their results suggested that an “obese microbiome” has an increased capacity to harvest energy from the diet, and that this type of obesity was “transmissible” by gut microbiota. (3)

Returning to the brown bear study Baeckhed’s group, the gut microbial changes observed when the bears were in a state of prolonged fasting and weight loss (increased abundance of Bacteroidetes, and reduced Firmicutes) were similar to the “lean human microbiota”, and the mirror image of the microbial changes observed in obese subjects further implicating the gut microbiota in the metabolic state of the organism.

As it is with most animal studies, extrapolation from the fascinating bear study to the cause of the human obesity epidemic and its treatment has to be done with caution. However, there are several important implications:

  • Obviously it would be great to identify the microbially produced chemicals that allows the bears to become obese summer after summer without developing metabolic consequences detrimental in human obesity.
  • Similarly, it would be of great interest to identify the microbial signaling molecules that are able to shut off the bear’s drive to eat when it is time to go into hibernation.
  • Intermittent fasting has been proposed as an effective way to loose weight and improve metabolic health, and several human studies support such a dietary regimen. (4)

Most importantly, like other recent studies in humans (5) they confirm that diet induced physiological oscillations in the gut microbiota’s diversity and relative abundance of different taxa have a significant influence on the metabolic state of the healthy organisms. The loss of such seasonal microbial oscillations in the microbiome of individuals living in developed countries, which have been showing a progressive and apparently irreversible decline in diversity is likely to play an important role in many chronic diseases, including type II diabetes and metabolic syndrome.

  1. Sommer F et al. The gut microbiota modulates energy metabolism in the hibernating brown bear Ursus arctos. Cell Reports 14: 1655-61, 2016
  2. Ley, R. E., et al.. Microbial ecology: human gut microbes associated with obesity. Nature. 2006 Dec 21;444(7122):1022-3.
  3. Peter J. Turnbaugh et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006 Dec 21;444(7122):1027-31.
  4. Patterson RE et al. Intermittent fasting and human metabolic health. J Acad Nutr Diet. 2015 Aug;115(8):1203-12. doi: 10.1016/j.jand.2015.02.018. Epub 2015 Apr 6.
  5. Smits SA et al. Seasonal cycling in the gut microbiome of the Hadza hunter gatherers of Tanzania. Science 357:802-6, 2017
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Fascinating study reporting results obtained from nearly 12,000 people around the world as part of the American Gut Project

Fascinating study reporting results obtained from nearly 12,000 people around the world as part of the American Gut Project

‘Largest’ microbiome study weighs in on our gut health

Fascinating study reporting results obtained from nearly 12,000 people around the world as part of the American Gut Project.  Major findings of this landmark study are the fact that it is the diversity of plant based foods that a person consumes (and not just the fact that somebody identifies as vegan or vegetarian) that influences gut microbial diversity and relative abundances, and that there is an association of mental disorders with gut microbial function, with gut microbial characteristics being more similar amongst several psychiatric diseases than compared to healthy individuals.  Even though the findings are solely based on associations, and do not allow to make statements about causality, they represent the most comprehensive analysis of gut microbial data published to date.