The Effect of a Diet Enriched with Jerusalem artichoke, Inulin, and Fluoxetine on Cognitive Functions, Neurogenesis, and the Composition of the Intestinal Microbiota in Mice

Well your doctor should have already put something together on inulin and fluoxetine already. But I guess you don't have a functioning doctor if nothing has been done with this earlier stuff. Why the fuck are you seeing and paying them for nothing? There are no excuses for such incompetence.

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Inulin research here:

The effect of addition protein, phosphatidylcholine, phosphatidylserine, and inulin on GFAP levels of acute ischemic stroke patients at Dr. Kariadi Hospital, Semarang June 2021 

Gut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice May 2020

Differential passage of [¹⁴C]sucrose and [³H]inulin across rat blood-brain barrier after cerebral ischemia November 2001

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Fluoxetine here:

• fluoxetine (22 posts to May 2014)

• simvastatin and fluoxetine drug combination (1 post to May 2016)

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The latest here:

The Effect of a Diet Enriched with Jerusalem artichoke, Inulin, and Fluoxetine on Cognitive Functions, Neurogenesis, and the Composition of the Intestinal Microbiota in Mice 

by

Aleksandra Szewczyk

^1,*,

Marta Andres-Mach

¹,

Mirosław Zagaja

¹,

Agnieszka Kaczmarczyk-Ziemba

²,

Maciej Maj

³ and

Joanna Szala-Rycaj

^1,*

¹

Department of Experimental Pharmacology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland

²

Department of Evolutionary Genetics and Biosystematics, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland

³

Department of Biopharmacy, Medical University of Lublin, Chodzki 4A, 20-093 Lublin, Poland

^*

Authors to whom correspondence should be addressed.

Curr. Issues Mol. Biol. 2023, 45(3), 2561-2579; https://doi.org/10.3390/cimb45030168

Received: 25 January 2023 / Revised: 21 February 2023 / Accepted: 18 March 2023 / Published: 21 March 2023

(This article belongs to the Special Issue Interstitial Cells of Cajal and Nervous System in Aging and Oxidative Stress)

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Abstract

The aim of the study was to assess the effect of long-term administration of natural prebiotics: Jerusalem artichoke (topinambur, TPB) and inulin (INU) as well as one of the most popular antidepressants, fluoxetine (FLU), on the proliferation of neural stem cells, learning and memory functions, and the composition of the intestinal microbiota in mice. Cognitive functions were assessed using the Morris Water Maze (MWM)Test. Cells were counted using a confocal microscope and ImageJ software. We performed 16S rRNA sequencing to assess changes in the gut microbiome of the mice. The obtained results showed that the 10-week supplementation with TPB (250 mg/kg) and INU (66 mg/kg) stimulates the growth of probiotic bacteria, does not affect the learning and memory process, and does not disturb the proliferation of neural stem cells in the tested animals. Based on this data, we can assume that both TPB and INU seem to be safe for the proper course of neurogenesis. However, 2-week administration of FLU confirmed an inhibitory impact on Lactobacillus growth and negatively affected behavioral function and neurogenesis in healthy animals. The above studies suggest that the natural prebiotics TPB and INU, as natural supplements, may have the potential to enrich the diversity of intestinal microbiota, which may be beneficial for the BGM axis, cognitive functions, and neurogenesis.

Keywords:

topinambur; inulin; fluoxetine; prebiotics; intestinal microbiota; neurogenesis; cognitive functions

1. Introduction

According to the most recent scientific estimates, there are about 3.8 × 10¹³ bacteria in the adult human body, which is 1.3 times more than human cells [1]. The totality of microorganisms in a specific environment is called the microbiota, and the collective genomes of all microorganisms are called the microbiome [2]. The human microbiome includes not only bacteria but also other microorganisms such as fungi, archaea, viruses, and protozoa [3].

The composition of the intestinal microbiota is an outcome of an interplay between numerous variables, such as a diet, an environment, host genetics, an exposure to infections, and an antibiotic usage [4]. Most of the human intestinal bacteria belong to four phyla: Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, with the Firmicutes and Bacteroidetes predominating. The equilibrium of the gut’s diverse microbial population is essential for preserving the host’s state of health [5].

In general, gut microbiome is beneficial for the human host. These microorganisms are key players in regulating gut metabolism, and are necessary to understand metabolism dysfunctions. For instance, there are connections between gut bacteria and the synthesis of vitamins B and K, short-chain fatty acid (SCFA) production, pathogen growth inhibition, preservation of intestinal barrier integrity and mucosal immune homeostasis, and involvement in the xenobiotic metabolism system [6,7].

The gut, the gut microbiota, and the brain are involved in a constant two-way communication that is referred to as the brain–gut–microbiome (BGM) axis [8,9]. Research on the BGM axis primarily includes the studies of pre- or probiotics as well as antibiotics in animal models [10,11,12,13], studies in germ-free (GF) animals [14], and fecal transplants [15]. This allows the identification of pathways that regulate BGM signaling between the digestive tract and the brain, including neural, endocrine, and immune pathways. It has been shown that the BGM axis plays an important role in the formation and maintenance of cognitive functions [16,17,18,19]. Moreover, the BGM axis was proved to be significant in the regulation of neurogenesis, one of the most essential processes of proliferation, migration, and differentiation of new neural cells [20,21,22,23]. Undoubtedly, one of the key factors negatively affecting the BGM and the neurogenesis is stress [24,25,26,27].

BGM is crucial in maintaining a proper homeostasis, and several psychiatric and nonpsychiatric illnesses have been proved to be at least in part responsible its dysfunction [28,29,30]. It should also be noted that, in addition to diseases, the composition and diversity of the gut microbiota can be affected by drugs used to treat the disorder, especially antibiotics. However, recent studies have shown that non-antibiotic drugs, such as the antipsychotics and antidepressants, also affect the intestinal microbiota [31,32]. Few studieshave been done so far to determine how the antidepressants affect the microbiota in the gut. One of them concerns research on fluoxetine hydrochloride (FLU), an antidepressant drug belonging to the group of selective serotonin reuptake inhibitors (SSRIs) used in depression, panic attacks, anxiety, or obsessive–compulsive symptoms [33,34]. The in vitro studies carried out so far have provided information that FLU has antimicrobial activity [35], whereas in vivo studies have shown its negative effect on the composition of the intestinal microbiome in both rats [35] and mice [36].

For years, we utilized probiotic bacteria in addition to food to maintain a healthy microbiome or to rebalance the system [37]. Probiotics are live bacteria and yeasts that have a beneficial effect onhuman health. The impact of probiotics may also be favored by prebiotics, which can be used as an alternative to probiotics or as their additional support [38]. Prebiotics are non-digestible food components that specifically promote the development of probiotic bacteria in the gut, including lactobacilli and bifidobacteria [39]. However, various prebiotics will promote the growth of different native gut bacteria [38]. The presence of prebiotics in the diet hasmany beneficial effects on the gut, the immune system, and brain function, particularly, brain-derived neurotrophic factor (BDNF) expression and N-methyl-D-aspartate (NMDA) receptor signaling. Substances classified as prebiotics are oligosaccharides, including galactooligosaccharides(GOS), transgalactooligosaccharides(TOS), xylooligosaccharides(XOS), fructooligosaccharides(FOS), isomaltooligosaccharides(IMO), as well as polysaccharides such as inulin (INU), cellulose, pectin, hemicellulose, or reflux starch [38].

INU is composed of fructose residues connected by β-(2,1) glycosidic linkages, and it plays the role of spare material in plants. INU is abundantly present in a variety of root vegetables including topinambur(TPB), banana, chicory, leek, and onion. TPB, a tuberous perennial plant of the Asteraceae family commonly known as wild sunflower or Jerusalem artichoke, has 160–200 g of INU per kilogram of fresh weight [40,41]. According to the study done thus far, TPB has several health-promoting qualities, including lowering blood glucose, triglycerides, LDL cholesterol, and total cholesterol [42]. In addition, TPB supplementary diet has an additive impact on the probiotic bacteria in the gut of rats [43] and mice [41].

Taking into account the above data, the aim of this study was to determine the impact of the long-term supplementation with prebiotics, TPB, and INU, in the form of natural compounds and 2-week administration of the antidepressant drug FLU, on the development of probiotic bacteria necessary for the proper functioning of the BGM axis, and thus their influence on cognitive functions and neurogenesis in healthy mice.

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