New research explores how the cycle of weight loss and gain, known as yo-yo dieting, alters the gut microbiome and hormones, leading to inflammation and weight gain, and offers insights into potential therapeutic interventions.
Study: The relationship between yo-yo dieting, weight loss after obesity, and gut health. Image credit: RVillalon/Shutterstock
In a recently published review in the journal Nutrients, researchers from Deakin University in Australia investigated the effects of yo-yo dieting and weight loss after obesity on gut health, focusing on gut inflammation, changes in the microbiome, sympathetic nervous system responses, and potential therapeutic targets to prevent weight gain.
background
Obesity affects more than half of the adult population worldwide and causes millions of deaths each year from diseases such as cardiovascular disease, type 2 diabetes, and fatty liver disease.
Losing weight sustainably remains difficult, resulting in the so-called “yo-yo dieting” phenomenon, with most people regaining all the weight they lost within five years.
Yo-yo dieting increases the risk of obesity-related complications and may cause gut microbiota dysbiosis leading to obesity and metabolic dysfunction.
Emerging evidence suggests that weight gain may alter the gut microbiota, highlighting the need for further research to understand the role of the gut in weight fluctuations.
Additionally, studies have pointed to adaptive metabolic responses, including changes in the sympathetic nervous system, which may further complicate efforts to maintain weight loss.
The effect of the gut on weight gain after weight loss
Weight gain after weight loss, which is common with yo-yo dieting, remains a complex issue as we don’t fully understand all the contributing factors.
However, current evidence suggests that changes in peripheral peptides regulating energy balance and metabolic adaptation play an important role.
This includes reduced activation of beta-adrenergic signaling via the sympathetic nervous system, which influences thermogenesis and energy expenditure, both of which are important for maintaining weight loss.
These changes can lead to decreased energy expenditure and increased food intake, both of which lead to weight gain and obesity.
Gut peptide hormones and energy balance
Regulation of energy balance involves the regulation of energy intake, expenditure, and storage, which are important drivers of body weight change.
Energy balance is not only controlled by the central nervous system, but is also influenced by peripheral signals from organs such as the gut, pancreas, and adipose tissue. Many of these signals are peptide hormones that act to stimulate or limit energy intake, thus influencing body weight.
Gut-derived peptide hormones, such as peptide tyrosine-tyrosine (PYY), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), and oxyntomodulin (OXM), play important roles in regulating feeding behavior by promoting satiety and reducing food intake.
Conversely, the hunger hormone ghrelin stimulates appetite, promotes fat storage, and accelerates carbohydrate metabolism. An imbalance of these hormones in favor of the hunger hormones often leads to weight gain as energy intake exceeds expenditure.
Research shows that when you lose weight, your levels of the satiety hormones (PYY, GLP-1, CCK) often decrease, while your levels of the hunger hormone (ghrelin) increase, making you more susceptible to overeating and weight gain.
This hormonal imbalance can persist long after weight loss and cause the body to regain weight as a way to restore energy balance.
Decreased levels of satiety hormones may also be linked to impaired regeneration of enteroendocrine cells (EECs), the intestinal cells that produce these hormones, which may make it more difficult to sustain weight loss.
Gut hormones, weight gain, and yo-yo dieting
The cyclical nature of weight loss and gain in yo-yo dieting is influenced by gut hormones: when you lose weight, your body responds by lowering levels of satiety hormones and increasing hunger signals, making it harder to maintain the weight loss.
Additionally, dramatic fat loss can reduce enteroendocrine cells (EECs) responsible for producing gut hormones, further reducing the body’s ability to regulate satiety.
With yo-yo dieting, the long-term hormonal imbalance between hunger and satiety hormones promotes a tendency to overeat, especially in the post-diet phase when weight gain is more likely.
Additionally, adaptations in the sympathetic nervous system reduce the body’s resting energy expenditure, further promoting weight regain by conserving energy after a period of caloric restriction.
The role of gut microbiota in weight gain
The gut microbiota, the collection of microorganisms living in the digestive tract, is crucial for regulating energy balance and metabolism.
Research suggests that gut microbiota composition and diversity change during and after weight loss, which may influence susceptibility to weight regain.
For example, short-chain fatty acids (SCFAs) produced by gut bacteria stimulate the secretion of satiety hormones such as PYY and GLP-1. However, yo-yo dieting is associated with a decrease in SCFA-producing bacteria, which can lead to reduced production of satiety hormones and increased appetite, which can lead to weight gain again.
Additionally, animal studies suggest that yo-yo dieting alters the composition of the gut microbiome, decreasing beneficial bacteria such as Christensenella and Lactobacillus reuteri, which are associated with leanness and gut health.
Conversely, weight gain after dieting is associated with an increase in pro-inflammatory bacteria such as Desulfovibrio and Ruminococcus, which are linked to metabolic disorders and intestinal inflammation.
Yo-yo dieting and intestinal inflammation
Chronic low-level inflammation is a hallmark of obesity, and yo-yo dieting exacerbates this problem. Studies have shown that weight gain following yo-yo dieting can trigger an inflammatory response in the gut, increasing the expression of pro-inflammatory markers such as tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6).
These inflammatory responses may further disrupt intestinal barrier function, increase intestinal permeability, and worsen metabolic health.
Animal studies suggest that weight gain following yo-yo dieting increases intestinal inflammation, with significant increases in inflammatory markers and macrophage activation.
Weight loss after obesity and gut health
Yo-yo dieting leads to intestinal inflammation and gut microbiota disruption, but weight loss after obesity has been shown to improve gut health: weight loss reduces inflammatory markers such as TNF-α and IL-6 in the gut and improves gut barrier function.
Additionally, successful weight loss has been linked to favorable changes in the gut microbiome, including an increase in beneficial bacteria such as Akkermansia and Bifidobacteria, which lead to improved gut health and reduced inflammation.
However, studies have also shown that it may take a significant amount of time for the microbiota composition to revert to a non-obese state following weight loss, and weight regain may be more likely during this transitional period.
Clinical studies also suggest that dietary interventions aimed at weight loss may positively influence the composition of the gut microbiota, potentially reducing the risk of regaining weight.
For example, flavonoids, bioactive compounds found in fruits and vegetables, have been shown to improve gut microbiota composition and promote weight maintenance in animal models.
Research gaps
Although current research highlights an important link between yo-yo dieting and gut health, significant gaps remain, particularly regarding the long-term effects of weight gain and loss on the gut microbiome and its role in weight gain.
Most of the evidence comes from animal models, and more human studies are urgently needed to explore how yo-yo dieting affects gut inflammation, microbiota composition, and hormone balance in humans.
Understanding these mechanisms may provide new therapeutic targets to prevent weight gain and improve long-term weight maintenance.
Conclusion
In summary, new evidence is emerging linking yo-yo dieting with alterations in the gut microbiota that may persist after weight loss and lead to weight gain.
Weight loss may improve gut health, but the molecular mechanisms behind this relationship remain unclear, particularly how gut-derived peptides, the sympathetic nervous system, and the intestinal barrier are affected.
Further research, especially in humans, is needed to fully understand the complex interactions between gut health, weight gain and loss, and obesity.
Journal References:
Phuong-Nguyen K, McGee SL, Aston-Mourney K, et al. “Yo-yo dieting, weight loss after obesity, and the relationship to gut health.” Nutrition. 2024; 16(18):3170, DOI – 10.3390/nu16183170, https://www.mdpi.com/2072-6643/16/18/3170
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