The gut microbiota: a key player in obesity and weight management

Specific gut bacteria and/or metabolites could be responsible for the differential responses to weight management.
Table of Contents

What is already known
The gut microbiota has a direct impact on the processing of food and can affect body weight by changing appetite, metabolism, hormones and bile acid metabolism. It provides protection and influences the intestinal environment, and alteration in microbiota composition has been observed in obese individuals.

What this research adds
Several dietary components, such as fat and protein, influence the gut microbiota and ultimately impact the host’s energy metabolism through specific microbial products. However, no specific bacteria can predict obesity or weight loss in humans so far.

Conclusions
Many metabolites produced and/or modified by the gut microbiota can be used as drug targets and further research is needed to develop personalized approaches for modulating the gut microbiota.

A recent review published in Nature reviews endocrinology, reports the progress made in understanding how the gut microbiota composition is involved in obesity. 

In particular it highlights how specific gut bacteria and/or metabolites could be responsible for the differential responses to weight management. Attention is also given to specific dietary regimens that can influence weight management by acting on the microbiota. 

Factors in the diet that impact the gut microbiota

Diet is the major factor shaping the composition of gut microbiota and fat and proteins are among the main factors affecting microbiota richness and diversity. 

An in-depth study from Suriano and colleagues, showed that dietary fat is the major determinant of body adiposity in mice and high-fat diet has been linked to a lower abundance of Bacteroides-like bacteria and increased risk of obesity. Diets containing omega-3 fatty acids are protective against obesity and other metabolic disorders, thanks to an increased number of Bifidobacterium, Lactobacillus and Akkermansia muciniphila

High-proteins diets are usually suggested for weight loss, but the quality of proteins consumed seems to affect the gut microbiota. A recent study revealed how a typical western diet leads to weight gain and insulin resistance in mice, due to microbial production of branched-chain fatty acids. 

As dietary protein intake is one of many factors affecting the host-microbiome dynamic, future research is needed to understand the interactive effects of proteins, carbohydrate and lipid profiles on weight loss. 

The role of microbiota in body weight regulation

The gut microbiota regulates host metabolism and weight status through alteration of calories absorption and production or modulation of compounds that impact metabolic pathways. 

Important microbial compounds include short-chain fatty acids (SCFAs) (i.e propionate), and its increase may prevent weight gain and regulate appetite in overweight adults, suggesting that boosting SCFA production may be an effective way to prevent obesity. 

Other important metabolism regulators are bile acids that have been suggested to play a role in energy expenditure changes in obese individuals

Weight loss strategies through microbiota modulation

The rise in obesity rates observed in the last decades is mainly linked to a sedentary lifestyle and the consumption of high calories food. However, the traditional weight loss approach through low calories diet and exercise is often challenging. 

Since gut microbiota composition may play a role in the variability of weight loss responses to diet interventions, various approaches are currently being studied for weight management, including altering gut microbiota composition for better health outcomes. 

In 2020, Ang and colleagues conducted a study on adult men with overweight or obesity who were given either a standard diet or a ketogenic diet for 4 weeks each. Switching between diets lead to changes in the abundance of Actinobacteria, Bacteroidetes and Firmicutes phyla. Bifidobacteria decreased the most on the ketogenic diet and these changes were driven by carbohydrate restriction, rather than high fat intake. 

The benefits of the Mediterranean diet (MedDiet) on obesity-related metabolic disorders have also been demonstrated. A randomized controlled study was conducted on healthy individuals with overweight or obesity who were assigned to a personalized MedDiet which increased fiber, polyunsaturated fatty acids, and reduced the saturated fatty acids. 

The study showed shifts in the gut microbiota composition, with more Faecalibacterium prausnitzii, Roseburia, and less Ruminococcus gnavus and Ruminococcus torques in the MedDiet group compared to the control group. Participants with reduced insulin resistance had higher levels of Bacteriodes uniformis and Bacteroides vulgatus and lower levels of Prevotella copri at baseline. All of these effects were observed independently of energy intake, underlining the importance of the type of nutrients instead of their caloric content. 

An increasingly popular dietary strategy is the intermitting fasting, that alternates between periods of fasting and periods of eating. Studies on Muslims during Ramadan, have shown an increase in beneficial gut bacteria, microbial richness and diversity, as well as levels of the beneficial SCFA butyrate

Several trials also showed that intermittent fasting led to weight loss of 0.813% in overweight or obese individuals over a period of 2 weeks to 1 year without adverse effects. However, controversial results have been found, therefore more research is needed to understand the role of this dietary regimen in weight loss and its potential mechanisms involving the gut microbiota.  

A recent post-hoc analysis found that individuals characterized by a high Prevotella-to-Bacteroides (P:B) ratio lose more weight on diets rich in dietary fibre than individuals with low Prevotella abundance (low P:B ratio), due to the interactions between the actual diet consumed and the efficacy of energy harvest by the microbiota. 

Since different people will have varying success on different diets, personalized nutrition may offer more effective obesity management strategies. It has been shown that gut microbiota can predict individual post-meal blood sugar levels, and that gut microbial profiles could be used to design personalized dietary interventions to improve postprandial glucose levels and related metabolic issues. 

Conclusions

Weight loss is a difficult goal to achieve and maintain due to gradual decrease of basal metabolic rate leading to weight regain. One of the best and longest-lasting option for achieving substantial weight loss is bariatric surgery, which causes significant changes in the gut microbiota composition and is believed to contribute to weight loss and metabolic improvement. 

A recent research on mice colonized with stool samples from patients before and after bariatric surgery, showed that some gut microorganisms could improve glucose tolerance, regardless of changes in fat mass, by controlling intestinal glucose absorption. Interestingly, the gut microbiota before surgery has been linked to the surgery outcomes, potentially explaining differences in response among individuals and offering the potential to predict results. 

Given the evident link between gut microbiota and obesity, fecal microbiota transplant (FMT), that replaces the gut microbiota of obese patients with that of lean and healthy donors, is considered a possible treatment strategy for obesity and metabolic syndrome. 

In conclusion, it is clear that the gut microbiota plays a significant role in the development of metabolic disorders and obesity, although no specific microbe has been proven to cause obesity or make it difficult to lose weight. 

Restoring the gut microbiota’s diversity and normal function is crucial for maintaining normal metabolism and homeostasis. This can be achieved through dietary interventions, prebiotics, probiotics, and medication. However, more research is needed to develop personalized recommendations on effectively modifying the gut microbiota.