Post-bariatric surgery quality-of-life decline: analysis of the gut–brain axis

Abstract

Purpose

Bariatric surgery has proven effective in enhancing metabolic health and achieving sustainable weight loss for individuals with obesity. However, some patients experience adverse psychological outcomes and reduced quality-of-life post-surgery, potentially linked to changes in the gut–brain axis. This review aims to synthesize current evidence on the interplay between bariatric surgery-induced gut–brain axis modifications and patients’ psychological status.

Methods

A systematic literature search was conducted across PubMed, Web of Science, and Embase, prioritizing clinical studies, mechanistic investigations, and meta-analyses. Inclusion criteria encompassed English-language articles examining psychological parameters, gut-derived hormones, and gut microbiota in adults after Roux-en-Y gastric bypass or sleeve gastrectomy.

Results

Bariatric surgery fundamentally reprograms gut–brain communication through anatomical, endocrine, and neural plasticity mechanisms, a process associated with dual-edged metabolic benefits and neuropsychiatric risks. Mechanistic analyses suggest that postoperative dysregulation of GLP-1/PYY secretion, altered vagal afferent signaling, and sustained microbiota dysbiosis (reduced Bifidobacterium, elevated Proteobacteria) may represent potential correlates of these outcomes.

Conclusions

Studies have demonstrated significant associations between mood, quality of life, psychological status, and gut-derived hormones or microbiota. A comprehensive understanding of how bariatric surgery impacts gut–brain signaling pathways is critical for optimizing long-term therapeutic outcomes and enhancing patient quality of life.

Level of evidence

This manuscript is a Narrative Review. According to the grading criteria of the Oxford Centre for Evidence-Based Medicine (OCEBM), this manuscript is categorized as Level III–IV evidence.

Introduction

Obesity, a chronic metabolic disease, is characterized by excessive accumulation and/or abnormal distribution of body fat, leading to increased body weight, resulting from the interaction of various factors, including genetics and environment [1]. Based on statistics provided by the World Health Organization (WHO), the prevalence of obesity worldwide has been tripling since 1975, becoming a global public health challenge. Obesity is tightly linked to a range of medical disorders, including metabolic syndrome (including abdominal obesity, hyperglycemia, hyperlipidemia, hyperuricemia), heart and blood vessel diseases (concerning high blood pressure, coronary artery disease, stroke, arteriosclerosis), respiratory diseases (such as asthma and sleep apnea syndrome), and certain types of cancer. In addition, obese patients are prone to psychological disorders, such as low self-esteem, depression, and anxiety, potentially linked to a decline in quality of life. They are also susceptible to neurological diseases (e.g., stroke, dementia, Parkinson’s disease) as well as mental/psychiatric conditions including sleep disorders. In short, diseases related to obesity cover almost all organs of the body and the field of mental health [2–4].

With the continuous rise in global obesity rates, bariatric surgery for treating obesity-related diseases has become an urgent need in clinical research. The success of the first bariatric surgery in the 1950s marked the beginning of a progressive era in surgical weight management. With the continuous advancement of bariatric surgery techniques, procedures such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have demonstrated their efficacy in markedly enhancing the metabolic health of patients with obesity and in achieving sustainable weight loss. Moreover, RYGB and SG, especially the latter, have low complication rates. As a result, bariatric surgery has been rapidly promoted worldwide. According to the American Society for Metabolic and Bariatric Surgery (ASMBS), in 2020, Laparoscopic Sleeve Gastrectomy (LSG) accounted for 62% of all the bariatric operations conducted in the United States and about 85% in China, making it the most common method of bariatric surgery. Nowadays, bariatric surgery has been acknowledged as an effective intervention for treating obesity and its accompanying comorbidities. It can not only significantly reduce body weight but also improve or cure a variety of obesity-associated diseases, such as type 2 diabetes, high blood pressure, and sleep apnea. The New England Journal of Medicine reported on a study indicating that 75% of individuals undergoing gastric bypass surgery achieved successful regulation of their diabetes within a 2-year timeframe following the procedure [5]. In addition, bariatric surgery also promotes mental well-being and improves the life quality for patients. However, for some people who have undergone bariatric surgery, their quality of life not only does not improve after surgery but also declines.

The phenomenon of decreased quality of life has attracted widespread attention in the medical community. Researchers have begun to delve into and study the potential mechanisms behind the decline in post-bariatric surgery life quality, among which the role of the gut–brain axis has gradually emerged, becoming a subject of intense research interest. The gut–brain axis represents the bidirectional communication link between the gut and the brain’s central nervous system. The operation of this axis involves the interaction of neural transmission, hormone secretion, and the gut microbiome, which collectively impact various physiological and psychological processes in the human body. The notion of the gut–brain axis offers a fresh outlook for evaluating the impact of bariatric surgery on life quality [6]. After bariatric surgery, changes in the function and anatomical structure of the digestive tract are associated with alterations in the normal operation of the gut–brain axis, which may in turn be linked to changes in patients’ emotions, quality of life, and behavior. A retrospective meta-analysis involving 32 quality-of-life-related items or measures indicates that compared to the control group, post-operative bariatric patients have a significantly higher likelihood of experiencing psychological issues, including substance use disorders, emotional fluctuations, anxiety, and even depression, which researchers suggest may be associated with imbalance of the gut–brain axis [7].As research continues to delve deeper, more and more evidence shows that considering the neuroendocrine changes of the gut–brain axis as a candidate for exploring associations between bariatric surgery and reduced life quality is logical. In light of this, this review, against the backdrop of the two main types of bariatric surgery, provides an in-depth analysis of the gut–brain axis’s role in the reduction of life quality after gastric surgery.

The operational mechanisms of RYGB and sleeve gastrectomy

RYGB surgery divides the patient’s stomach into upper and lower parts, creating a small-capacity gastric pouch (15–30 ml) at the junction, where the esophagus meets the stomach. The pouch is then connected to the lower part of the small intestine, or jejunum, which allows food to bypass the rest of the stomach and the initial portion of the small intestine. To reestablish the flow of the digestive system and to enable the mixing of bile and pancreatic juices with the food in the jejunum, a second anastomosis is created between two parts of the jejunum, located 100–150 cm away from the point, where the small intestine is joined to the gastric pouch. Sleeve gastrectomy involves placing a 32–40 Fr calibrating gastric tube into the stomach through the mouth, typically starting the resection 2–6 cm away from the pylorus, following the calibrating gastric tube closely and moderately taut, cutting continuously towards the gastric fundus until the fundus is transected 0.5–1 cm from the His angle. Subsequently, the gastric resection margin is reinforced from the fundus to the pylorus [8, 9]. After this surgery, the remaining stomach volume of the patient is approximately 100 ml. Both bariatric surgery methods achieve weight loss by reducing stomach volume, limiting food intake, decreasing the rate of food absorption, and slowing the speed of eating. However, studies on adjustable gastric banding have found that even when the postoperative gastric pouch volume is controlled at 30 ml, its weight loss effect is still not as significant as that of sleeve gastrectomy. This research result implies that the reduction in stomach capacity is not the only factor contributing to decreased energy intake and weight loss.

The gastrointestinal tract’s feedback regulation of the brain’s appetite center also has an essential function. In the gut–brain axis’s appetite regulation pathways, ghrelin is recognized as the primary hormone possessing appetite-stimulating properties, chiefly released by the P/D1 cells in the gastric fundus and the ε cells in the pancreas. Notably, these cell groups are located in the surgical resection area of sleeve gastrectomy. After bariatric surgery, the decline in ghrelin levels is not the only significant change in gut hormones. Glucagon-like peptide-1(GLP-1) and peptide YY (PYY) are also two representative hormones, the concentrations of which are significantly increased after surgery.GLP-1 increases sharply after meals and reaches its peak within 15–30 min. It delays the digestion and absorption process of food by inhibiting gastric emptying and reducing food intake. At the same time, it can effectively mitigate postprandial hyperglycemia. The production of PYY is similar to GLP-1; 15 min after eating, the ileal L cells begin to secrete PYY, but in such a short time, the chyme has not yet reached the ileum. This phenomenon indicates that the ileal L cells do not produce related hormones under the direct action of chyme but rely on other neuroendocrine regulatory mechanisms. PYY triggers responses by acting on the Y2 receptors of the NPY family. The Y2 receptors are scattered widely across the peripheral and central nervous systems, with a pronounced concentration in the arcuate nucleus of the hypothalamus, considered the central domain for hunger regulation. However, changes in gut hormones may be associated with fluctuations in mood and cognitive functions, such as increased anxiety and depressive symptoms, the occurrence of substance use disorders, and declines in memory and attention [10].

In addition, bariatric surgery not only is associated with changes in gastrointestinal hormones but also is linked to alterations in the intestinal flora. Clinical studies have demonstrated that after bariatric surgery, the diversity of gut bacteria decreases, but it is often the beneficial flora, such as Lactobacillus and Bifidobacterium, that exhibit reduced abundance, while pathogenic potential micro-organisms, particularly, Proteobacteria and Bacteroidetes, increase in abundance. Such transformations are connected to weight reduction and optimized metabolic activity, and at the same time, they are linked to variations in intestinal barrier and immune responses. Such shifts in the gut microbiota may be associated with changes in the local intestinal environment; meanwhile, they may also be linked to alterations in brain function via the gut–brain axis, and these changes may in turn be related to modifications in psychological states, behaviors, and quality of life [10]. This process once again confirms that the delicate balance within the body and its complex interactions far exceed our traditional understanding of physiological mechanisms.

The gut–brain axis and its mechanistic effects on quality of life

The intestines, the longest organ within the human body, have their own dedicated nervous system, referred to as the Enteric Nervous System (ENS), which contains about 500 million neurons, comparable in number to those in the brain, forming what is known as "second brain." The ENS connects with the central nervous system through various pathways, including the ENS, the vagus nerve, the endocrine system, and the intestinal microbiota, forming the gut–brain axis. Post-bariatric surgery, alterations in the gastrointestinal tract’s anatomy and functionality are closely associated with changes in the back-and-forth communication of the gut–brain link. Taking RYGB as an example, this surgery reduces food intake and intestinal absorption area by shrinking stomach capacity and altering the route through which food bypasses the small intestine, thereby affecting food digestion and absorption. Studies have shown that patients who undergo RYGB may attain a mean weight loss of 30–40% of their original weight and significantly alleviate health risks associated with obesity, including type 2 diabetes, high blood pressure, and sleep apnea [5]. However, alterations in the intestinal architecture are associated with modifications to the neuroendocrine system and the gut microbiota, which in turn are linked to direct or indirect changes in brain function and emotional states, and these changes may be associated with negative impacts on patients’ quality of life. Therefore, in-depth analyses of the physiological mechanisms of the gut–brain axis is crucial for developing interventions aimed at reducing the decline in quality of life and adverse mental health outcomes following post-bariatric surgery.

Impact of the gut microbiota

The gut microbiota, which constitutes the normal microbial ecosystem within the human gut, can be broadly categorized into three groups: beneficial bacteria, harmful bacteria, and neutral bacteria. The number of these micro-organisms reaches approximately 10^{^14}, encompassing 500–1000 different microbial species. They are necessary agents in the food digestion and nutrient absorption process, defense against infections, control of the risk of autoimmune diseases, and regulation of the body’s response to cancer treatments. In the healthy adult’s intestinal microbiota, Firmicutes and Bacteroidetes account for up to 90% of the composition [11]. The balance of the gut microbiota is closely associated with the stability of the gut–brain axis. Disruption of this balance is associated with a decline in human health status. For instance, Studies have shown that a higher Firmicutes-to-Bacteroidetes ratio is correlated with the occurrence of obesity, and it has been reported that in obese populations, the gut microbiota exhibits reduced diversity and species richness [12, 13].

Following bariatric surgery, the structure of the gut microbiota undergoes significant changes, specifically, there is an increase in the relative abundance of Proteobacteria and Bacteroidetes, while the relative abundance of Firmicutes and Bifidobacterium decreases [14]. These alterations can persist for up to 9 years in humans [14, 15]. Over the past decades, the potential for gut microbiota to affect organs and their functions beyond the gastrointestinal system is a hot topic in the field of medical research. Studies have indicated that germ-free mice, which lack a balanced gut microbiota, exhibit abnormalities during early development in phenotype and neurochemistry, implying that the gut microbiota might affect quality of life and mental health; these abnormalities can be corrected by restoring a normal gut microbiota [16]. For instance, compared to healthy controls, patients exhibiting depression and anxiety have been found to have a reduced relative abundance of Firmicutes and an increased relative abundance of Bacteroidetes. This phenomenon suggests that the observed gut microbiota characteristics may be associated with the occurrence of depression and anxiety symptoms in some post-bariatric surgery patients, despite the lack of complete clarity on the mechanisms involved. However, through experimental manipulation of the gut microbiota composition or its metabolic byproducts, changes in the behavioral and physiological characteristics of rodents in depression models can be observed [17]. Further research has shown that transplanting fecal microbiota from depressed men into rats administered antibiotics or into germ-free mice causes the recipients to exhibit anhedonia, anxiety, and depressive behaviors [18, 19].

The rodent models have shown that manipulating the gut microbiota’s composition and metabolic outputs can significantly alter depressive and anxious behaviors, providing a solid experimental foundation for investigating the influence of gut bacteria on mental health. However, when extending the study findings to humans, the mechanisms by which the gut microbiota influences emotional states still demand deeper research for more conclusive proof. Nevertheless, this does not mean that there is a lack of empirical data to underpin this perspective. Multiple case–control studies between healthy individuals and those with depression and anxiety have provided support for an association between gut microbiota and mental health. For instance, the supplementation of probiotics, specifically, Bifidobacterium and Lactobacillus strains, when used to modulate the gut microbiota, can alleviate symptoms of anxiety and depression, lower cortisol levels, and reduce the amygdala’s reactivity to fear-inducing stimuli [20].

The research on the correlation between variations in gut microbiota composition and function and emotional states following bariatric surgery in humans still requires further in-depth exploration. However, with the continuous advancement of technology, we have ample reason to believe that by precisely regulating the gut microbiota, we can substantially elevate the health conditions and life quality for individuals who have undergone bariatric surgery.

Impact of gut endocrine hormones on mood

The gut endocrine cells, distributed within the mucosal layer of the gastrointestinal system, can sense mechanical, chemical, and neural stimuli within the lumen, including food intake, nutrient absorption, and contact with microbial byproducts. In response to these stimuli, these cells release multiple hormones and peptides that can influence neighboring intestinal cells (paracrine), disperse into the bloodstream via the lamina propria (endocrine), or activate the vagus nerve and sensory nerve fibers that innervate the intestinal wall and the enteroendocrine cells (neural), thereby producing systemic effects [21]. The various hormones and peptides secreted by enteroendocrine cells, such as GLP-1, ghrelin, PYY, and cholecystokinin (CCK), are crucial in regulating appetite and energy balance. Although SG and RYGB surgery have significant differences in anatomical structure, both can significantly reduce food intake, body mass, and glycemic levels, and there are some similarities in the circulating levels of enteroendocrine hormones. For example, both types of surgery can stimulate the release of a range of satiety hormones in response to food, including GLP-1, PYY, and CCK. These hormones not only act within the intestine but also transmit signals to the CNS via the gut–brain axis, which in turn impacts mood, quality of life, and cognitive performance [22].

L cells at the ileum’s extremity secrete GLP-1, and its functions include enhancing satiety, attenuating the rate of gastric emptying, and inhibiting intestinal motility. Post-bariatric surgery, GLP-1 concentrations undergo a substantial rise, thereby contributing to rapid weight loss. In addition, the GLP-1 receptor(GLP1-R)is abundantly present in areas of the brain that are directly tied to stress, reward, and mood regulation, including the paraventricular nucleus of the hypothalamus (PVN), the ventral tegmental area(VTA),the amygdala, and the hippocampus. This neural reflex pathway indicates that GLP-1 may play a potential part in regulating stress responses. Studies in rodent models have confirmed that GLP-1 is associated with changes in depressive and anxiety behaviors, but its effects are not constant. For example, a single dose of a peripheral GLP-1 receptor agonist before the forced swim test does not induce changes in depressive-like behaviors in mice; however, after continuous administration for 1–2 weeks, the agonist shows antidepressant-like effects [23]. In rats, however, a one-time central or peripheral application of a GLP-1 receptor agonist can cause anxiety-like behaviors, while chronic central administration does not modify anxiety or depressive-like behaviors [24].Clinical trials likewise demonstrate that intravenous injection of GLP-1 and its receptor agonists do not produce an anxiety-inducing effect in both healthy control groups and patients with panic disorder [25, 26].These research results reveal the complexity of gut hormones in the modulation of mood and quality of life, suggesting that when assessing and improving post-bariatric surgery life quality, we need to consider the dynamic effects of these biomolecules. At the same time, in-depth research on the mechanisms of GLP-1 and its receptor in mood regulation might introduce new biological markers for the intervention of psychological illnesses, such as depression and anxiety.

P/D1 cells in the fundus of the stomach and epsilon cells in the pancreas are the main sites of Ghrelin secretion. As an endogenous hormone, its role is to enhance hunger and intestinal motility, increase food intake, and thereby promotes weight gain. Ghrelin levels significantly decrease after bariatric surgery, and this may have a potential link with fluctuations in patients’ life quality postoperatively. In rodents, extensive research has explored the impact of ghrelin administration or blockade on anxiety and depressive behaviors, but these results are modulated by various factors, such as the external environment, timing, route of administration, dosage, and duration. For example, in rat experiments, if food is given within an hour after injecting ghrelin and before the behavioral test, the anxiolytic effect of ghrelin on the amygdala will no longer exist [27]. This result suggests that under conditions, where food is not accessible, amygdala ghrelin communication may be associated with the inhibition of anxiety-like responses. However, in ghrelin gene knockout mouse models, anxiety effects under acute stress are enhanced, while anxiety-like behaviors are reduced under non-stress conditions [28].Nonetheless, most rodent studies support an association between acute/chronic exposure to ghrelin, whether produced internally or externally, and antidepressant-like outcomes [29–31]. However, in clinical experiments, the correlation between ghrelin and emotional states has not been fully confirmed, and its specific mechanisms of action and clinical applications still require further in-depth exploration.

PYY secreted by L cells at the end of the ileum and belonging to the NPY neuropeptide family, significantly increases in secretion levels after bariatric surgery and activates NPY receptor subtypes. NPY along with its receptor types are extensively present across different areas of the brain, including the hippocampus, amygdala, the hypothalamic arcuate nucleus, and the nucleus accumbens [32]. The hippocampus, amygdala, and nucleus accumbens play key roles in the body’s stress response and emotional regulation, suggesting that PYY can influence emotions and behavior by acting on these brain areas. In fact, human studies on NPY expression or genetic variations also underscore the role of the NPY family in regulating emotional and behavioral states, particularly highlighting NPY’s anxiolytic properties [33, 34].

Bile acids, as key components of bile, are the ultimate products of cholesterol metabolism in the liver. In human physiology, bile acids play multiple crucial functions, including promoting the digestion and absorption of fats, maintaining cholesterol homeostasis, and stimulating the pancreas to secrete pancreatic juice. In particular, bile acids, beyond their function in fat metabolism, glucose metabolism, lipid and energy balance, may also affect emotional states. Notably the Farnesoid X receptor(FXR),as a bile acid receptor, is highly expressed in both the liver and intestine, as well as in the neurons of the cerebral cortex and hippocampus [35].Animal experimental results show that mice and rats with FXR gene deficiency exhibit abnormal neurobehavioral and biochemical indicators, such as reduced depression-like and anxiety-like behaviors, as well as a drop in brain-derived neurotrophic factor (BDNF) expression [36, 37]. However, such research has not been fully conducted in the field of clinical experiments; therefore, studying the impact of bile acids on emotional regulation after bariatric surgery presents certain difficulties.

CCK is synthesized from 33 amino acids and was initially extracted from the proximal small intestine, subsequently located in several brain regions, among them the cerebral cortex, hippocampus, amygdala, hypothalamus, and ventral tegmental area [38].To date, the peripheral effects of CCK have been extensively studied. Cholecystokinin can promote gastric acid and bile secretion, and at the same time, it curbs sodium absorption in the ileum and water absorption process, and stimulates the release of insulin and glucagon. In addition, substances such as protein breakdown products, fatty acid salts, and hydrochloric acid can stimulate the secretion of CCK, which in turn continuously transmits satiety signals to the hypothalamus, suppressing the generation of appetite. CCK not only acts on the hypothalamus but also affects regions in the cerebral cortex and limbic system that participate in emotional responses and regulation, including the amygdala, hippocampus, and VTA. In human studies, intravenous infusion of cholecystokinin tetrapeptide (CCK4) can induce panic attacks in those suffering from anxiety disorders and healthy individuals [39]. However, this outcome can be prevented by pre-administering CCKR2 antagonists [39–41].It is worth noting that long-term use of CCK antagonists in humans (for more than 4–6 weeks) has not improved symptoms of anxiety or panic disorders [42, 43],but the use of anti-anxiety drugs can effectively reduce individuals’ sensitivity to CCK4-induced panic effects. This phenomenon indicates that CCK’s role in anxiety is influenced by its engagement with other biological signaling pathways [44].

The impact of gut endocrine hormones on addictive behaviors

After bariatric surgery, gut endocrine hormones not only affect mood and psychological status but also involve the regulation of addictive behaviors. Researchers have begun to pay attention to the fact that patients after bariatric surgery may seek rewards in other areas to compensate for the psychological void brought about by a decrease in food eaten. Studies have shown that these hormones can act on the brain’s reward system, which may be associated with alterations in an individual’s dependence on substances, such as food, drugs, nicotine, or alcohol. The regulation of the reward system covers both the intake of food and drugs and is also related to an individual’s behavioral patterns and social activities [45]. Accumulating evidence reveals an increased risk of alcohol use disorders following RYGB and SG [46],and there may also be issues with the use of other drugs(especially opioids) [47–49].In addition, some case reports have revealed new cognitive behavioral conditions in patients, for instance, gambling or shopping addiction. The "addiction transfer" hypothesis has been proposed, suggesting that someone might cultivate a new" addictive" behavior instead of the satisfaction and pleasure brought by preoperative eating [50]. However, at present, this hypothesis lacks scientific basis.

Interestingly, initially, research on the postoperative effects of bariatric surgery on alcohol use disorders showed a positive effect, with a decrease in both the desire for and consumption of alcohol [51]. However, as research on bariatric surgery continues to delve deeper, approximately 50% of patients halted their alcohol-seeking behavior in the first year subsequent to RYGB. After the initial year, a boost in alcohol consumption and the incidence of alcohol use disorders was noted from the second year, with these rates remaining high for several years after RYGB [52].Numerous studies corroborate this finding, indicating that RYGB has led to an increase in alcohol intake among patients who had a lower baseline alcohol intake before surgery [52–54].

Patients are at risk of developing substance use disorders after bariatric surgery, and in cases of drug abuse treatment, a disproportionately high proportion of patients are those who have had bariatric surgery [54].Alarmingly, many of the substance use disorders that emerge postoperatively are new occurrences [55, 56].Research on individuals who had bariatric surgery and later joined inpatient substance abuse rehabilitation found that over 50% had no prior substance use [56, 57].This leads us to ponder whether there is a correlation between bariatric surgery and changes in cognitive behavior.

Studies to date have indicated that central ghrelin signaling may be a potential mechanism for changes in alcohol reward following RYGB [58].In studies on rodents, food and alcohol seeking behaviors are mediated by central ghrelin signaling at the growth hormone secretagogue receptor(GHSR) within the VTA [59, 60].This mechanism could explain the changes in alcohol consumption and/or reward mechanisms observed after RYGB [61, 62]. Furthermore, in alcohol-preferring rats that received RYGB, the reduction in alcohol consumption was associated with elevated GLP-1 concentrations in the blood plasma. For rats undergoing sham surgery, the use of a GLP1-R agonist initiated an equivalent reduction in alcohol consumption. In addition, ghrelin replacement was followed by restoration of the drinking behavior in rats that preferred alcohol, but it did not have any effect on rats that were sham-operated [63, 64].Overall, these results validate that GLP-1 and ghrelin may contribute to the initial decrease in alcohol consumption noted following RYGB. However, further studies are necessary to explore the roles of ghrelin, GLP-1, and other gut endocrine hormones. The function of gastrointestinal hormones in addiction to other substances, such as opioids, post-bariatric surgery is yet to be ascertained.

Limitations

It is important to acknowledge several limitations to this study. First, heterogeneity in the quality-of-life assessment instruments employed by the included studies introduces potential bias into the findings. Second, the extensive scope of this review has precluded a sufficiently comprehensive and in-depth synthesis of all involved domains. Furthermore, the majority of clinical evidence is derived from short-to-medium-term follow-up (≤ 5 years), precluding the formulation of definitive conclusions regarding the long-term adaptive responses of the gut–brain axis. Finally, in certain sections of this review, studies utilizing rodent models constitute a relatively high proportion, whereas human clinical data remain limited. In addition, the translational validity of these animal models to human outcomes has not been fully established, which may contribute to overstatement of the reported results.

Discussion

Bariatric surgery is an established obesity management intervention that significantly improves metabolic profiles, achieves effective and sustained weight loss, and maintains long-term weight stability. This procedure operates through multiple mechanisms: beyond its weight-reducing effects, it is closely linked to changes in patients’ quality of life and psychological well-being. To date, the majority of studies have demonstrated that bariatric surgery enhances post-operative quality of life and psychological status; however, a small subset of patients experience diminished quality of life and adverse psychological changes following surgery. This review provides an in-depth analysis of the potential mechanism underlying this phenomenon—the gut–brain axis. Despite some inconsistent findings, accumulating evidence indicates that alterations in gut–brain axis signaling pathways post-bariatric surgery are associated with mental health and quality-of-life outcomes.

To date, neither the association between the gut–brain axis and post-surgical changes in mental health and quality of life nor the translational validity of animal model findings to clinical trials has been scientifically established. Therefore, in addition to further elucidating the complex interplay within the gut–brain axis, future research should prioritize the following study designs to advance the field: validating rodent-derived mechanisms in large-scale human randomized controlled trials (with IRB approval), such as probiotic supplementation for gut dysbiosis (e.g., Bifidobacterium strains) [14, 20] and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for addictive behavior transfer intervention [63, 64];Developing a quality-of-life database specific to Chinese patients using validated cross-cultural adaptation protocols, with scores from diverse assessment tools converted to standardized mean differences (SMDs) to strengthen result comparability and reliability; Implementing long-term standardized monitoring and assessment (≥ 10 years) of post-bariatric surgery patients’ quality of life, gut hormone levels, and gut microbiota profiles to generate robust longitudinal data. Such research has the potential to deliver more comprehensive and durable health benefits to patients.

Conclusion

Through an in-depth exploration of these mechanisms, researchers hope to reveal the specific associations between bariatric surgery and life quality, thereby further optimizing surgical plans to provide personalized treatment services for patients. At the same time, this will help clinical doctors to more accurately identify potential psychological risks in the preoperative assessment process, and formulating corresponding preventive measures.

In future research, with the aid of advanced scientific and technological methods, it will be possible to more comprehensively analyze the mechanisms of the gut–brain axis, offering innovative therapeutic approaches to improve patients’ postoperative quality of life. This will not only promote the personalized development of surgical plans but also provide a scientific basis for psychological health interventions, which will help in formulating targeted preoperative consultations and postoperative support plans, ensuring that patients achieve comprehensive physical and mental health improvements during the weight loss process.

On this basis, interdisciplinary cooperation will be crucial. By integrating research findings from various fields, such as endocrinology, psychology, and nutrition, a more comprehensive treatment system can be established for patients, thereby better meeting their needs and improving treatment outcomes.

Author contributions

As the first author, YXJ was responsible for determining the topic and scope of the manuscript, systematically searching for and screening relevant literature, writing the main body of the review, and integrating the contributions of the other authors.In addition, YXJ also revised the manuscript multiple times to ensure the accuracy and coherence of the content and worked closely with the corresponding author to complete the final submission of the manuscript. SHZ and HCX provided expert advice on the selection of the topic and the research direction of the manuscript. SHZ and HCX also offered key academic insights during the process of literature screening and analysis and conducted a detailed review and revision of the initial draft. DH conducted an initial evaluation of the overall structure and content of the manuscript and reviewed and revised the manuscript. YHW and YFW assisted with the collection and organization of the literature materials. All authors have reviewed the manuscript.

Funding

No funding.

Data availability

No datasets were generated or analyzed during the current study.

Declarations

Competing interests

The authors declare no competing interests.