Lactobacillus reuteri strain 8008 attenuated the aggravation of depressive-like behavior induced by CUMS in high-fat diet-fed mice through regulating the gut microbiota

Abstract

Objective: Gut microbiota play a key role in the pathogenesis of obesity and depression. Probiotics are a preventive strategy for obesity and a novel treatment for depression symptoms. However, the ameliorative or therapeutic effect of potential probiotic candidate Lactobacillus reuteri (L. reuteri) on obesity and depression comorbidity still remains unclear. We investigated the effects of chronic unpredictable mild stress (CUMS) in high-fat diet-fed mice and the effects of Lactobacillus reuteri strain 8008 on various disease indicators of obesity and depression comorbidity disease.Methods: Forty male C57BL/6 mice were randomized into 2 groups: the normal control (NC) group (n = 10) and the high-fat diet (HFD) group (n = 30), being fed with normal diet (ND) or high-fat diet (HFD) for 8 weeks, respectively. Then the obese mice fed with HFD were randomly allocated into 3 sub-groups: the HFD group (n = 10); the HFD + CUMS group (n = 10); the HFD + CUMS + L.r group (n = 10). The latter 2 subgroups underwent CUMS for 4 weeks to build the obesity and depression comorbidity mice model. During the duration of treatment, mice were gavaged with 0.5 mL PBS solution or L. reuteri (2 × 109 CFU/mL) once a day, respectively. The body weight, food intake, organ weight, behavioral indicators, histology, blood lipids, levels of inflammatory cytokines and tight junction proteins and abundance of colonic contents bacteria were measured.Results: The obesity and depression comorbidity mice model was successfully established after HFD feeding and chronic stress. The comorbid mice demonstrated inflammatory responses increase in liver and adipose tissues, worsened damage to the intestinal barrier as well as gut microbiota disorder. Gavaged with L. reuteri attenuated depressive-like behavior, improved blood lipids and insulin resistance, reduced inflammation in liver and adipose tissues, improved intestinal tight junctions as well as the microbiome dysbiosis in obesity and depression comorbidity mice.Conclusion:Lactobacillus reuteri strain 8008 could alleviate depressive-like behaviors and related indicators of obesity disorders by regulating the gut microbiota in obesity and depression comorbid mice.

The Probiotic Lactobacillus reuteri Preferentially Synthesizes Kynurenic Acid from Kynurenine

“…For example, increased formation and release of KYNA by L. reuteri may regulate the enteric nervous system [75], affect the growth and viability of probiotic bacteria in the digestive system [76], alleviate various gastrointestinal pathologies [77] and have anti-inflammatory effects by inhibiting Th17 cell differentiation and the increase in TNFα in monocytes and leukocytes [20,78]. Notably, though the mechanistic link clearly needs to be investigated further, KYNA generated by L. reuteri-alone or in combination with other probiotics-may also participate in the attenuation of depressive-like symptoms associated with chronic stress [41] and in the reduction of obesity-related behavioral impairments and related microglial activation [42,43,46].…”

“…Lactobacillus (L.) reuteri, a well-studied probiotic bacterium that colonizes the gastrointestinal tract of both humans and animals, can influence the composition of the gut microbiota [41] and has been shown to exert a remarkable range of beneficial effects in both humans and relevant animal models. Notably, L. reuteri administration affects neurodevelopment and prevents social deficits and depressive-like behaviors in experimental animals [41][42][43][44][45][46][47]. Interestingly, though the underlying mechanisms have not been identified so far, L. reuteri is able to normalize the impaired plasma levels of KP metabolites caused by chronic stress and to improve associated behavioral abnormalities [35].…”

Research trends on the gut microbiota in endocrine metabolism: a thematic and bibliometric analysis

“…The WoSCC, recognized for its extensive interdisciplinary scope, hosts over 170 million articles from more than 250 academic disciplines (Shi et al, 2022). Specifically, the database hosts a significant volume of literature pertinent to our study, with a considerable number of articles and cited references directly related to gut microbiota research within the realm of endocrinology and metabolism (Zhang et al, 2022;Li C. et al, 2023;Xue et al, 2023;Takeuchi et al, 2023). Given the database's extensive usage and acclaim in scientometric research, it provides a solid basis for analyzing the trajectory of gut microbiota research in our field.…”

“…Building upon this, targeted research has illuminated the roles of specific bacteria. Studies have demonstrated that Lactobacillus reuteri and Akkermansia muciniphila show a negative correlation with serum LPS levels and fasting plasma glucose levels (Shi et al, 2022;Li C. et al, 2023). This indicates these bacteria become a potential therapeutic target for reducing serum LPS levels and improving glucose metabolism.…”

Lactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms

“…Wu and colleagues found that L. reuteri reconstructed the epithelial integrity by activating the Wnt/bcatenin pathway, thereby promoting the intestine epithelial cell proliferation and inducing intestinal stem cell differentiation to Paneth cells, even under the condition of TNF-induced intestinal inflammation (Wu et al, 2020). On the other hand, L. reuteri was also reported to maintain the integrity of the gut barrier by upregulating the expression of TJ proteins, evidenced in in preclinical studies (Gao et al, 2022;Liu et al, 2022a;Li et al, 2023a). TJ proteins are primary for epithelial cell proliferation and gut permeability (Kuo et al, 2021).…”