Yoyo dieting alters gut health, driving weight regain and inflammation

New research explores how the cycle of losing and regaining weight, known as yoyo dieting, alters gut microbiota and hormones, leading to inflammation and weight regain, offering insights into potential therapeutic interventions.

In a recent review published in the journal Nutrients, researchers at Deakin University, Australia, explored the impact of yoyo dieting (the repeated cycle of losing and regaining weight) and post-obesity weight loss on gut health, focusing on gut inflammation, microbiota changes, sympathetic nervous system responses, and potential therapeutic targets for preventing weight regain.

Background 

Obesity affects over half of the global adult population and contributes to millions of deaths each year from diseases like cardiovascular disorders, type 2 diabetes, and fatty liver disease.

Sustained weight loss remains a challenge, with most individuals regaining lost weight within five years, a phenomenon known as yoyo dieting.

Yoyo dieting increases the risk of obesity-related comorbidities and may involve gut dysbiosis, which is linked to obesity and metabolic dysfunction.

Emerging evidence suggests weight regain could alter gut microbiota, highlighting the need for further research to understand the gut's role in weight cycling.

In addition, research points to adaptive metabolic responses, including changes in the sympathetic nervous system, which may further complicate efforts to maintain weight loss.

The Influence of the gut in weight regain after weight loss

Weight regain following weight loss, commonly observed in yoyo dieting, remains a complex issue without a complete understanding of all contributing factors.

However, current evidence suggests alterations in peripheral peptides that regulate energy balance and metabolic adaptation play a significant role.

This includes reduced activation of β-adrenergic signaling through the sympathetic nervous system, which impacts thermogenesis (heat production) and energy expenditure, both of which are critical for maintaining weight loss.

These changes may lead to reduced energy expenditure and increased food intake, both of which contribute to weight regain and obesity.

Gut peptide hormones and energy balance

Regulation of energy balance involves adjusting energy intake, expenditure, and storage, which are critical drivers of body weight changes.

Energy balance is not only controlled by the central nervous system but also influenced by peripheral signals from organs such as the gut, pancreas, and adipose tissue. These signals, many of which are peptide hormones, act to either stimulate or restrict 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 critical roles in regulating feeding behavior by promoting satiety and reducing food intake.

Studies suggest that after weight loss, individuals often experience lower levels of satiety hormones (PYY, GLP-1, and CCK) and higher levels of hunger hormones (ghrelin), making them more prone to overeating and weight regain.

This hormonal imbalance may persist long after weight loss, driving the body to regain weight as a means of restoring energy balance.

Reduced levels of satiety hormones may also be associated with impaired renewal of enteroendocrine cells (EECs), the gut cells responsible for producing these hormones, potentially exacerbating the difficulty of sustaining weight loss.

Gut hormones, weight regain, and yoyo dieting

The cyclical nature of weight loss and regain in yoyo dieting is influenced by gut hormones. When individuals lose weight, their bodies respond by reducing the levels of satiety hormones and increasing hunger signals, making it difficult to maintain weight loss.

In yoyo dieting, the prolonged hormonal imbalance between hunger and satiety hormones fosters a tendency to overeat, especially in the post-dieting phase, where the body is highly susceptible to weight regain.

Additionally, sympathetic nervous system adaptations reduce the body's resting energy expenditure, further promoting weight regain by conserving energy after periods of calorie restriction.

Gut microbiota's role in weight regain

The gut microbiota, the collection of microorganisms living in the gastrointestinal tract, is crucial for regulating energy balance and metabolism.

Sympathetic nervous system's role: Yoyo dieting reduces activation of the sympathetic nervous system, leading to lower energy expenditure and contributing to rapid weight regain after calorie restriction.

Animal studies further suggest that yoyo dieting alters the gut microbiota's composition, reducing beneficial bacteria such as Christensenella and Lactobacillus reuteri, which are linked to leanness and gut health.

Conversely, weight regain after dieting is associated with an increase in pro-inflammatory bacteria, such as Desulfovibrio and Ruminococcus, both of which are implicated in metabolic disorders and gut inflammation.

Yoyo dieting and gut inflammation

Chronic low-grade inflammation is a hallmark of obesity, and yoyo dieting exacerbates this issue. Studies have shown that weight regain following yoyo dieting can trigger inflammatory responses in the gut, with increased expression of pro-inflammatory markers like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).

These inflammatory responses can further disrupt gut barrier function, leading to increased intestinal permeability and worsening metabolic health.

Post-obesity weight loss and gut health

Although yoyo dieting contributes to gut inflammation and dysbiosis, post-obesity weight loss has been shown to improve gut health. Weight loss reduces inflammatory markers in the gut, such as TNF-α and IL-6, and improves intestinal barrier function.

Moreover, successful weight loss is associated with favorable changes in the gut microbiota, such as increased abundance of beneficial bacteria like Akkermansia and Bifidobacterium, which are linked to enhanced gut health and reduced inflammation.

However, research also indicates that microbiota composition may take much longer to return to a non-obese state after weight loss, potentially making individuals vulnerable to weight regain during this transition period.

Clinical studies also suggest that dietary interventions targeting weight loss can positively influence gut microbiota composition, potentially reducing the risk of weight regain.

For instance, 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

While current studies highlight important links between yoyo dieting and gut health, significant gaps remain, particularly regarding the long-term effects of weight cycling on the gut microbiota and its role in weight regain.

Most of the evidence comes from animal models, and there is a pressing need for more human studies to explore how yoyo dieting influences gut inflammation, microbiota composition, and hormonal balance in humans.

Understanding these mechanisms could provide new therapeutic targets to combat weight regain and improve long-term weight maintenance.

Conclusions 

To summarize, emerging evidence links yoyo dieting to changes in gut microbiota, which may persist after weight loss and contribute to weight regain.

While weight loss can improve gut health, the molecular mechanisms behind this relationship remain unclear, particularly how gut-derived peptides, the sympathetic nervous system, and the gut barrier are affected.

More research is needed, especially in humans, to fully understand the complex interactions between gut health, weight cycling, and obesity.

Journal reference:

• Phuong-Nguyen K, McGee SL, Aston-Mourney K, et al. Yoyo Dieting, Post-Obesity Weight Loss, and Their Relationship with Gut Health. Nutrients. 2024; 16(18):3170, DOI - 10.3390/nu16183170, https://www.mdpi.com/2072-6643/16/18/3170