Lactobacillus reuteri FYNLJ109L1 Attenuating Metabolic Syndrome in Mice via Gut Microbiota Modulation and Alleviating Inflammation

Cheng

et al. 2022

Preprint

Background Lactoferrin is an active protein in breast milk that plays an important role in the growth and development of infants and is implicated as a neuroprotective agent. The incidence of depression is currently increasing, and it is unclear whether the lack of lactoferrin during lactation affects the incidence of depression in adulthood. Objectives The purpose of our work was to investigate the effect of lactoferrin feeding deficiency during lactation on adult depression and related mechanisms. Methods Lactoferrin knockout mice provided lactoferrin-free milk to establish a lactoferrin feeding deficiency model during lactation. The chronic unpredictable mild stress (CUMS) depression model was established when the mice reached 9 weeks of age. Behavioural performance, serum indicators, and the microbiota, intestine, and hippocampus injury of the CUMS mice were investigated; RNA-seq of the small intestine and hippocampus, and gut microbiota compositions in 18-day-old lactoferrin-free mice were analysed; the development of the intestine and hippocampus and microbiota compositions in adult lactoferrin-free mice were also examined. Results Lack of lactoferrin feeding during lactation affected the barrier and innate immune functions of the intestine, disrupted the intestinal microflora, and led to neuroimmune dysfunction and neurodevelopmental delay in the hippocampus. When exposed to external stimulation, adult lactoferrin feeding-deficient mice presented with worse depression-like symptoms; the mechanisms involved were activation of the LPS–TLR4 signalling pathway in the intestine and hippocampus, reduced BDNF signalling pathway in hippocampus, increased abundance of depression-related bacteria, and decreased abundance of beneficial bacteria. Conclusions Overall, our findings reveal that feeding lactoferrin during lactation can reduce the risk of depression in adults. The mechanism is related to the regulatory effect of lactoferrin on the development of the "microbial–intestinal–brain" axis.

Section: Effect Of Lf Feeding De Ciency During Lactation On Gut Micro...supporting

confidence: 88%

Lactoferrin Feeding Deficiency during Lactation Increases the Risk of Depression in Adult Mice by Affecting Microbiota-Gut-Brain Axis Development

Cheng

et al. 2022

Preprint

Section: Effect Of Lf Feeding De Ciency During Lactation On Gut Micro...supporting

confidence: 87%

Lactoferrin feeding deficiency during lactation increases the risk of depression in adult mice by affecting microbiota-gut-brain axis development

Cheng

et al. 2022

Preprint

Background Lactoferrin is an active protein in breast milk that plays an important role in the growth and development of infants and is implicated as a neuroprotective agent. The incidence of depression is currently increasing, and it is unclear whether the lack of lactoferrin during lactation affects the incidence of depression in adulthood. Objectives The purpose of our work was to investigate the effect of lactoferrin feeding deficiency during lactation on adult depression and related mechanisms. Methods Lactoferrin knockout mice provided lactoferrin-free milk to establish a lactoferrin feeding deficiency model during lactation. The chronic unpredictable mild stress (CUMS) depression model was established when the mice reached 9 weeks of age. Behavioural performance, serum indicators, and the microbiota, intestine, and hippocampus injury of the CUMS mice were investigated; RNA-seq of the small intestine and hippocampus, and gut microbiota compositions in 18-day-old lactoferrin-free mice were analysed; the development of the intestine and hippocampus and microbiota compositions in adult lactoferrin-free mice were also examined. Results Lack of lactoferrin feeding during lactation affected the barrier and innate immune functions of the intestine, disrupted the intestinal microflora, and led to neuroimmune dysfunction and neurodevelopmental delay in the hippocampus. When exposed to external stimulation, adult lactoferrin feeding-deficient mice presented with worse depression-like symptoms; the mechanisms involved were activation of the LPS–TLR4 signalling pathway in the intestine and hippocampus, reduced BDNF-CREB signalling pathway in hippocampus, increased abundance of depression-related bacteria, and decreased abundance of beneficial bacteria. Conclusions Overall, our findings reveal that feeding lactoferrin during lactation can reduce the risk of depression in adults. The mechanism is related to the regulatory effect of lactoferrin on the development of the "microbial–intestinal–brain" axis.

“…For identifying significantly different species across groups, the LDA score was used in our study (Figure 6). L. reuteri and B. pseudolongum were considerably different in the Rnls +/+ -ND group, and both have been described as probiotics in previous studies [41][42][43]. S24-7 and Lactobacillus were considerably different in the Rnls −/− -ND group, and both have been reported by decreasing the risk of obesity [44].…”

Section: Discussionmentioning

confidence: 67%

Effects of High-Fat Diet on the Gut Microbiota of Renalase Gene Knockout Mice

et al. 2022

Metabolic diseases caused by gene and unhealthy living habits are increasing, which seriously threaten the life of people worldwide. Moreover, the microbiome has been shown to play an active role in the prevention and treatment of metabolic diseases. However, reliable evidence on renalase gene (Rnls), as a common gene related to metabolic diseases, is still lacking with regard to the influence on the microbiome. Hence, we investigated the effect of a normal diet (ND) and a high-fat diet (HFD) on the gut microbiota of Rnls knockout (Rnls−/−) and wild-type (Rnls+/+) mice. At the end of the 8-week experiment, DNA samples were extracted from fresh feces, and the composition of microbiota was profiled. The species in Rnls+/+-ND group were Bifidobacterium pseudolongum and Lactobacillus reuteri. Conversely, the species in Rnls−/−-ND group belonged to the genera Lactobacillus and Turicibacter. The HFD changed the ratio of Firmicutes/Bacteroidetes; while the bacteria in the Rnls+/+-HFD and Rnls−/−-HFD groups were different. Overall, this study not only revealed the composition of microbiota in Rnls−/− mice, but also indicated that Rnls and the bacteria related to Rnls may be new candidates in the prevention and diagnosis of metabolic diseases at an early stage.