Investigating the Impact of the Gut Microbiome on Obesity

Obesity is a growing global concern, with the prevalence rising steadily in many countries across the world. A person is generally considered to be obese if they have laid down excessive amounts of fat that increase their body weight to 20% or more above their recommended weight.  

Since obesity is a major risk factor for several life-threatening chronic diseases, including diabetes, cardiovascular diseases, and cancer, there are numerous efforts underway to reverse this epidemic.

Diet is a key factor in the development of obesity. If an individual consistently consumes more energy than they utilize, the excess will be laid down as fat.

It has also been shown that diet plays an important role in shaping the composition of the gut microbial community1. Furthermore, the microbes present in the gut change very rapidly as the diet in altered2. Knowing that obesity is closely linked to diet and that diet affects the gut microfauna, the relationship between bacterial colonization of the gut and obesity is now being investigated.

gut microbiome

© Alpha Tauri 3D Graphics/

In particular, it appears that the sugar mannose can greatly affect metabolism, weight gain, and the composition of gut bacteria in rodents. These effects are being investigated as a potential target for the development of new treatments and prevention strategies for obesity.

The gut microbiome

The colonies of bacteria that reside in the gastrointestinal tract are collectively known as the gut microbiome3.  It typically comprises over 100 trillion microscopic and living organisms, which help with the healthy functioning of the gut in a variety of ways. These include providing nutrients and energy and combatting infection. Disruption of the balance of the gut microbiome, for example through diet or illness, can give rise to a variety of gastrointestinal symptoms, and sometimes more serious complications4.

The importance of the gut microbiome is highlighted by the impact changes in the microbial composition has on host pathways, such as energy regulation, systemic inflammation, enteroendocrine signaling, and gut barrier function. Most recently, studies in mice models indicate that there is also a relationship between the activities of the gut microbiota and obesity5. Transplantation of the fecal microbiomes from an obese human adult germ-free mice caused the mice to also lay down excessive fat and caused changes in serum levels of branched-chain amino acids6.

The monitoring of patients treated with the sugar mannose for the rare condition congenital disorder of glycosylation (CDG) revealed that it also impacted the propensity of a patient to put on weight. Consequently, the sugar was investigated as a potential treatment for obesity.

Mannose and obesity

Mannose is an important monosaccharide for protein glycosylation in mammals but is an inefficient cellular energy source.

Researchers have recently studied the effects of mannose in a mouse model of diet-induced obesity7. Mice aged 3 weeks or 8 weeks were fed a normal diet with or without added mannose or a high-fat diet with or without mannose added. Body weight was measured weekly and fat mass was determined every 2 or 3 weeks in conscious mice a Bruker LF90II TD-NMR spectrometer for 3-4 months. Blood sugar levels, liver fat content, and overall fitness were also monitored.

The mice on a high-fat diet who received mannose supplementation were found not to put on weight, have lower adiposity, reduced liver steatosis, improved glucose tolerance, and increased endurance and O2 consumption7. In addition, the mice on mannose-supplemented diets had a higher fecal energy content, suggesting that they were absorbing fewer calories.  

Interestingly, these beneficial effects of mannose were only observed in the 3-week-old mice. This indicates that mannose is required early in life before the onset of obesity in order to provide its protective effects.

Furthermore, when mannose was removed from the diet, the mice gained weight and their bacterial composition returned to that of the obese rodents who had not received mannose supplementation.

Analysis of the gut microbiome revealed that mannose increased the ratio of Bacteroidetes to Firmicutes, a signature associated with the lean phenotype. Providing mannose thus prevented high-fat-diet-induced obesity in mice. As was seen with the effects of mannose on weight gain, mannose increased the Bacteroidetes:Firmicutes ratio more when started early (2.3-fold at 0 weeks vs 1.5-fold when started at 3 weeks), and unaltered (1.1-fold) when not initiated until 8 weeks. This confirms the link between obesity and microbiota.

These new data suggest that the gut microbiota contributes to mannose-induced resistance to the deleterious effects of a high-fat diet.


  1. Carmody RN, et al. Cell Host Microbe2015;17:72-84.
  2. David CF, et al. Nature 2014;505:559-563.
  3. Wu GD, Lewis JD. Clin Gastroenterol Hepatol. 2013;11(7):774-777.
  4. Gut bacteria and IBS. International Foundation for Functional Gastrointestinal Disorders Website.
  5. Everard C, et al. Proc. Natl. Acad. Sci. USA 2013;110:9066-9071.
  6. Ridaura JJ, et al. Science 2013;341:1241214
  7. Sharma V, et al. Mannose Alters Gut Microbiome, Prevents Diet-Induced Obesity, and Improves Host Metabolism. Cell Reports 2018;24(12):3087-3098.

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Last updated: Mar 11, 2022 at 12:36 AM


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