Obesity and the Human Microbiome

Conclusion

An increasing number of studies relate imbalances in the composition of the gut microbiota to obesity and its associated diseases. The approaches used to characterize gut microbiotas vary widely, which might explain in part why the specific alterations in the microbiota associated with excess body fat, or weight loss, can also vary between studies. To compare studies will require some standardization of approaches or use of a variety of approaches within single studies. However, irrespective of the specific changes observed in microbial communities with respect to body fat, evidence suggests that microbes do indeed respond and contribute to host energy balance. They may do this using a number of different and possibly interactive signaling mechanisms involving innate immune responses, endocrine cells, and epithelial cells. An integration of mechanistically based investigations and microbial ecology studies using high-throughput sequencing will provide insights into how best to reshape host-microbial interactions to promote health.

Table 1. Human studies of gut microbial ecology in relation to body weight
Author	Participants	Method (sample type)	Finding
Ley et al.^[2]	12 obese participants on one of two diets, carbohydrate or fat-reduced, for 1 year; two lean controls	16S rRNA surveys by Sanger sequencing (feces)	Proportion of Bacteroidetes sequences increased over time, on average, and correlated with weight loss. No difference between diets
Turnbaugh et al.^[5••]	154 participants, MZ and DZ twins and mothers, obese or lean	16S by Sanger and 454 pyrosequencing, metagenomics (feces)	Reduced levels of diversity, and reduced levels of Bacteroidetes in obese participants; metagenomes of obese participants enriched in energy-harvesting genes
Schwiertz et al.^[6]	30 lean, 35 overweight, 33 obese participants	qPCR for Bacteroidetes, Actinobacteria, Archaea (feces)	More Bacteroidetes in overweight and obese vs. lean participants, and more Methanobrevibacter in lean participants
Collado et al.^[7]	Women before and during pregnancy, 18 overweight participants and 36 controls	FISH/flow cytometry and qPCR (feces)	Higher levels of Bacteroidetes and S. aureus in overweight, positive correlation between Bacteroides levels and weight gain over pregnancy
Sotos et al.^[8]	8 obese and overweight adolescents during weight loss	FISH (feces)	Enterobacteriaceae and sulfate-reducing bacteria reduced in group with greatest weight loss. Reduced levels of Roseburia–Eubacterium in those with less weight loss
Duncan et al.^[9]	Participants on weight loss diets over 8 weeks vs. weight maintenance	FISH counts (feces)	No difference in Bacteroidetes levels between groups; reduced levels of Roseburia and Eubacterium, and increased levels of Clostridium spp., correlate with reduced carbohydrate intake
Kalliomaki et al.^[10••]	Obese and overweight children (n=25) and normal weight children (n=24); prospective study	qRT-PCR and FISH/flow cytometry (feces)	Children remaining lean at age 7 had higher levels of Bifidobacteria and lower levels of S. aureus, as infants
Santacruz et al.^[11•]	36 adolescents on diet and physical activity, 10 weeks	qPCR (feces)	Bacteroides fragilis abundance correlated with carbohydrate intake. Levels of Bacteroides and Lactobacillus increased with weight loss
Nadal et al.^[12]	39 adolescents on diet and physical activity, 10 weeks	qPCR (feces)	Clostridium histolyticum and E. rectale–C. coccoides reduced with weight gain; increase in Bacteroides–Prevotella in high weight loss group
Sabate et al.^[13]	137 obese patients, 40 healthy controls	Glucose-hydrogen breath test (for H₂) and liver biopsy (breath, liver)	Bacterial overgrowth in small intestine more common in obese vs. lean participants
Zhang et al.^[14•]	3 lean, three obese, and three postgastric bypass participants	Sanger and 454 sequencing of 16S rDNAs, qPCR (feces)	Firmicutes more abundant in lean participants, lowest after gastric bypass. Gamma-Proteobacteria and Verrucomicrobia enriched after gastric bypass; higher Archaea in obese participants; overall communities of gastric bypass and obese participants more similar to each other than to lean participants

Table 1. Human studies of gut microbial ecology in relation to body weight

Author

Participants

Method (sample type)

Finding

Ley et al.^[2]

12 obese participants on one of two diets, carbohydrate or fat-reduced, for 1 year; two lean controls

16S rRNA surveys by Sanger sequencing (feces)

Proportion of Bacteroidetes sequences increased over time, on average, and correlated with weight loss. No difference between diets

Turnbaugh et al.^[5••]

154 participants, MZ and DZ twins and mothers, obese or lean

16S by Sanger and 454 pyrosequencing, metagenomics (feces)

Reduced levels of diversity, and reduced levels of Bacteroidetes in obese participants; metagenomes of obese participants enriched in energy-harvesting genes

Schwiertz et al.^[6]

30 lean, 35 overweight, 33 obese participants

qPCR for Bacteroidetes, Actinobacteria, Archaea (feces)

More Bacteroidetes in overweight and obese vs. lean participants, and more Methanobrevibacter in lean participants

Collado et al.^[7]

Women before and during pregnancy, 18 overweight participants and 36 controls

FISH/flow cytometry and qPCR (feces)

Higher levels of Bacteroidetes and S. aureus in overweight, positive correlation between Bacteroides levels and weight gain over pregnancy

Sotos et al.^[8]

8 obese and overweight adolescents during weight loss

FISH (feces)

Enterobacteriaceae and sulfate-reducing bacteria reduced in group with greatest weight loss. Reduced levels of Roseburia–Eubacterium in those with less weight loss

Duncan et al.^[9]

Participants on weight loss diets over 8 weeks vs. weight maintenance

FISH counts (feces)

No difference in Bacteroidetes levels between groups; reduced levels of Roseburia and Eubacterium, and increased levels of Clostridium spp., correlate with reduced carbohydrate intake

Kalliomaki et al.^[10••]

Obese and overweight children (n=25) and normal weight children (n=24); prospective study

qRT-PCR and FISH/flow cytometry (feces)

Children remaining lean at age 7 had higher levels of Bifidobacteria and lower levels of S. aureus, as infants

Santacruz et al.^[11•]

36 adolescents on diet and physical activity, 10 weeks

qPCR (feces)

Bacteroides fragilis abundance correlated with carbohydrate intake. Levels of Bacteroides and Lactobacillus increased with weight loss

Nadal et al.^[12]

39 adolescents on diet and physical activity, 10 weeks

qPCR (feces)

Clostridium histolyticum and E. rectale–C. coccoides reduced with weight gain; increase in Bacteroides–Prevotella in high weight loss group

Sabate et al.^[13]

137 obese patients, 40 healthy controls

Glucose-hydrogen breath test (for H₂) and liver biopsy (breath, liver)

Bacterial overgrowth in small intestine more common in obese vs. lean participants

Zhang et al.^[14•]

3 lean, three obese, and three postgastric bypass participants

Sanger and 454 sequencing of 16S rDNAs, qPCR (feces)

Firmicutes more abundant in lean participants, lowest after gastric bypass. Gamma-Proteobacteria and Verrucomicrobia enriched after gastric bypass; higher Archaea in obese participants; overall communities of gastric bypass and obese participants more similar to each other than to lean participants

Obesity and the Human Microbiome

Conclusion

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References

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