Combined probiotics attenuate chronic unpredictable mild stress-induced depressive-like and anxiety-like behaviors in rats

Abstract

Increasing evidence indicated that probiotics can be effective in improving behaviors similar to depression and anxiety disorders. However, the underlying mechanisms remain unclear, as is the effects of single vs. combined probiotics on depression and anxiety. This study aimed to determine whether combined probiotics could attenuate depressive-like and anxiety-like behavior induced by chronic unpredictable mild stress (CUMS) and its potential mechanisms. Rats underwent CUMS treatment and then administered Lactobacillus rhamnosus HN001 (HN001) or Bifidobacterium animalis subsp. lactis HN019 (HN019), alone or in combination. Levels of neurotransmitters, inflammatory factors, and the gut microbiota were measured. HN001 and (or) HN019 treatment improved depressive-like and anxiety-like behavior in rats, including increased moving distance and exploratory behavior (p < 0.05). In addition, altered gut microbiota structure induced by CUMS was amended by HN001 and/or HN019 (p < 0.05). HN001 and/or HN019 intervention also remarkably normalized levels of 5-HT, DA, NE, HVA, DOPAC, HIAA, TNF-α, IL-6, IL-18 and IL-1β in CUMS rats (p < 0.05). Furthermore, the effects of combined probiotics on decreasing inflammation and improved gut microbiota (Chao1 index and ACE index, p < 0.05) were superior to the single probiotics. Moreover, spearman analysis showed a certain correlation between the different microbiota, such as Firmicutes, Bacteroidetes, Verrucomicrobias, Proteobacterias and Actinobacterias, and inflammation and neurotransmitters. These findings suggested that CUMS induced depressive and anxiety-like behaviors can be alleviated by the combination of probiotics, which was possibly associated with the alterations in the gut microbiota composition and increased neurotransmitters and decreased inflammatory factors.

Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota–gut–brain axis in corticosterone combined with chronic restraint stress‐induced mice

“…In the antibiotic‐mediated microbiota‐depletion mouse model, ampicillin, gentamicin, metronidazole, neomycin (all at 0.25 mg/day), and vancomycin (0.125 mg/day) were given to all mice for 14 days to deplete gut microbiota. After a three‐day washout period, the recipient Control + Con‐FMT group and Model + Con‐FMT group mice were given 200 μL of donor supernatant from Control group and Model + Zzcd‐FMT group mice were given 200 μL of donor supernatant from ZZCD group by oral gavage every 2 days for 2 weeks 27,28 . The behavioral tests were performed for four consecutive days from FMT week 2.…”

“…After a threeday washout period, the recipient Control + Con-FMT group and Model + Con-FMT group mice were given 200 μL of donor supernatant from Control group and Model + Zzcd-FMT group mice were given 200 μL of donor supernatant from ZZCD group by oral gavage every 2 days for 2 weeks. 27,28 The behavioral tests were performed for four consecutive days from FMT week 2. Blood samples from the mice orbit was used for ELISA.…”

The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective

“…Indeed, some stress‐induced changes in gut physiology have been prevented or reversed by administration of Lactobacillus spp. (Huang et al., 2022; Jang et al., 2018; Li et al., 2019; Zareie et al., 2006) or Bifidobacterium spp. (Huang et al., 2022; Li et al., 2019; Tian, O'Riordan et al., 2020) in rodents.…”

“…(Huang et al., 2022; Jang et al., 2018; Li et al., 2019; Zareie et al., 2006) or Bifidobacterium spp. (Huang et al., 2022; Li et al., 2019; Tian, O'Riordan et al., 2020) in rodents. Additionally, emerging preclinical evidence indicates that stress exposure enriches pathogenic bacteria, such as Escherichia‐Shigella (Jang et al., 2018; Shaler et al., 2021).…”

Gut microbiota decreased inflammation induced by chronic unpredictable mild stress through affecting NLRP3 inflammasome

“…Our previous studies have found that chronic unpredictable mild stress (CUMS) stimuli induced depression-like behaviors, increased levels of IL-1β and IL-18 and altered the microbiota ( Huang et al., 2022 ), which suggested NLRP3 inflammasome might be activated. What’s more, intervention with combined probiotic reversed altered microbiota and reduced levels of inflammatory cytokines, further indicating that microbiota might be a key role in activating NLRP3 inflammasome and upregulating inflammation ( Mou et al., 2022 ).…”