Back in the 1960s, mouse model research led by the renaissance scientist René Dubos – Wikipedia uncovered intriguing and groundbreaking connections between gut microbiota composition, and body size and weight. These associations got forgotten for several decades. Meantime obesity rates started skyrocketing the world over in just the last few decades, too short a period of time for human genetic changes such as mutations alone to be the sole or main impetus.
Recent years have thus witnessed renewed research interest in the link between gut microbiota composition and metabolic issues such as obesity. If the environment shaped human gut microbiota more so than host genetics, recent changes in it could explain much of this recent propensity for weight gain. However, whether gut microbiota composition is a cause or effect of obesity, i.e., the nature of their association remains unclear.
- Back in 2005, a mouse model study from a prominent microbiota research lab at Washington University in St. Louis showed that a certain strain of genetically obese mice had greater proportion of Firmicutes and decreased proportion of Bacteroides bacteria compared to their wild type (normal) counterparts (1).
- In short order, the same group showed similar trends in obese versus lean humans, and even suggested weight loss through dietary changes increased Bacteroides and decreased Firmicutes in obese individuals (2).
Alas, increase Bacteroides, decrease Firmicutes turned out to be no magic weight loss formula.
Later studies simply didn’t replicate this association between obesity and relative proportions of these two bacterial phyla.
Final nails in the coffin were meta-analyses showing that variations between different studies exceeded whatever differences were observed between obese and lean individuals in a given study (3, 4). Confounding factors could explain such dissonance,
- Molecular biology techniques currently used to study human gut microbiomes are so sensitive and details of the methods used by different groups vary so much, it is presently difficult if not impossible to even sift signal from noise.
- Unlike inbred mouse strains used in biomedical research, humans are an outbred, genetically heterogeneous species.
- To name just a couple of obvious differences, lifestyle and diets vary tremendously between humans.
Studies on twins discordant for obesity, where one twin was obese while the other had normal weight, showed (5, 6),
- They have different gut microbiota composition. Indeed, studies find twin gut microbiomes became more dissimilar the longer they live apart (7, 8).
- Transferring stools from such individuals into germ-free mice replicated their metabolic features, i.e., germ-free mice that got stools from obese individuals developed more fat mass.
- Co-housing such mice led to the dominance of the lean phenotype. Mice are coprophagic (they eat poop) so the idea is co-housing allowed obese mice to get colonized by bacteria from lean mice while the reverse was not observed suggesting that, at least in such reductionist mouse models, gut microbiota associated with leanness dominated.
Preliminary studies suggest Fecal microbiota transplant – Wikipedia may be helpful in reversing some aspects of obesity such as glucose tolerance (9).
Beyond such generalities, nothing much can be asserted with certainty at present (late 2018). Claims that specific bacterial species in the form of probiotics can help anyone lose weight are outright misrepresentations.
Bibliography
1. Ley, Ruth E., et al. “Obesity alters gut microbial ecology.” Proceedings of the National Academy of Sciences 102.31 (2005): 11070-11075. Obesity alters gut microbial ecology
2. Ley, Ruth E., et al. “Microbial ecology: human gut microbes associated with obesity.” nature 444.7122 (2006): 1022. https://www.researchgate.net/pro…
3. Walters, William A., Zech Xu, and Rob Knight. “Meta‐analyses of human gut microbes associated with obesity and IBD.” FEBS letters 588.22 (2014): 4223-4233. Meta‐analyses of human gut microbes associated with obesity and IBD
4. Sze, Marc A., and Patrick D. Schloss. “Looking for a signal in the noise: revisiting obesity and the microbiome.” MBio 7.4 (2016): e01018-16. http://mbio.asm.org/content/7/4/…
5. Ridaura, Vanessa K., et al. “Gut microbiota from twins discordant for obesity modulate metabolism in mice.” Science 341.6150 (2013): 1241214. https://pdfs.semanticscholar.org…
6. Goodrich, Julia K., et al. “Human genetics shape the gut microbiome.” Cell 159.4 (2014): 789-799. Human Genetics Shape the Gut Microbiome
7. Xie, Hailiang, et al. “Shotgun metagenomics of 250 adult twins reveals genetic and environmental impacts on the gut microbiome.” Cell systems 3.6 (2016): http://572-584.https://www.sciencedirect.com/science/article/pii/S2405471216303234
8. Rothschild, Daphna, et al. “Environment dominates over host genetics in shaping human gut microbiota.” Nature 555.7695 (2018): 210. https://genie.weizmann.ac.il/pub…
9. Jayasinghe, Thilini N., et al. “The new era of treatment for obesity and metabolic disorders: evidence and expectations for gut microbiome transplantation.” Frontiers in cellular and infection microbiology 6 (2016): 15. The New Era of Treatment for Obesity and Metabolic Disorders: Evidence and Expectations for Gut Microbiome Transplantation