The Gut–Brain Axis within the Human Body

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Georgia Saxami	--	5123	2023-10-19 08:52:30	\|
2	layout	Camila Xu	-53 word(s)	5070	2023-10-19 09:45:57	\|

This entry is adapted from the peer-reviewed paper 10.3390/life13102023

The human gut microbiota (GM) is a complex microbial ecosystem that colonises the gastrointestinal tract (GIT) and is comprised of bacteria, viruses, fungi, and protozoa. The GM has a symbiotic relationship with its host that is fundamental for body homeostasis. The GM is not limited to the scope of the GIT, but there are bidirectional interactions between the GM and other organs, highlighting the concept of the “gut–organ axis”. Any deviation from the normal composition of the GM, termed ”microbial dysbiosis”, is implicated in the pathogenesis of various diseases. Only a few studies have demonstrated a relationship between GM modifications and disease phenotypes, and it is still unknown whether an altered GM contributes to a disease or simply reflects its status. Restoration of the GM with probiotics and prebiotics has been postulated, but evidence for the effects of prebiotics is limited. Prebiotics are substrates that are “selectively utilized by host microorganisms, conferring a health benefit”.

gut–organ axis gut microbiota dysbiosis prebiotics

1. Introduction

The significance of the GM to human health has been recognised for centuries; Hippocrates said, “Death sits in the bowls” in 400 B.C., and the term “microbiota” dates back to the early 1900s ^[1]. The human GM is the largest micro-ecosystem in the human body and is regarded as the “essential organ” ^[2]. The GM is a complex, dynamic, and spatially heterogeneous ecosystem comprised of a collection of bacteria, viruses, fungi, and protozoa that colonise the gastrointestinal tract (GIT) and interact with each other and the human host ^[3]. The human body harbours a nearly equal quantity of microbial cells, in comparison to human cells ^[4]. The regions with the highest microbial biomass are the caecum and proximal colon.

The GM profile of each individual is unique at the species and genus level and is influenced by several factors, such as genetics, diet, environmental conditions, lifestyle, early microbial exposure, and the immune system ^[5]. However, the relative abundance and distribution at the phylum level along the intestine are consistent among healthy individuals ^[6]. The gut of an adult individual is majorly dominated by six phyla, including Firmicutes (Clostridium, Lactobacillus, and Enterococcus), Bacteroidetes (Bacteroides), Actinobacteria (Bifidobacterium), Proteobacteria (E. coli), Fusobacteria, Verrucomicrobia, and Cyanobacteria, among which Firmicutes and Bacteroidetes are the major types ^[7]. Also, fungi, mainly Candida, Saccharomyces, Malassezia, and Cladosporium, are included in the GM, as are viruses, phages, and archaea, mainly Methanobrevibacter smithii ^[8]^[9].

The GM has a symbiotic relationship with the host, while it has a central role in maintaining the homeostasis of the human body, impacting various physiological functions, including metabolism, vitamin synthesis, barrier homeostasis, protection against pathogens, immune system development and maturation, and hematopoiesis via intestinal and extra-intestinal actions, having an effect on human behaviour and thereby making it a vital organ ^[3]^[10]. The influence of the GM is not limited to the scope of the GIT, but evidence from recent studies describes bidirectional interactions between the GM and other organs, highlighting the concept of the “gut–organ axis” (Figure 1). This cross-talk is mediated by a variety of signalling pathways and direct chemical interactions between the host and microorganisms ^[10]. Studies over the past five years have increased the understanding of the gut–brain axis, the gut–liver axis, the gut–lung axis, and the gut–heart axis ^[11].

Figure 1. Schematic diagram depicting the influence of GM dysbiosis on the gut–organ axis. GM dysbiosis leads to the degradation of mucin, disrupts the gut’s protective barrier, increases its permeability, and enables pathogenic microorganisms, along with their by-products and endotoxins, to infiltrate. This invasion results in the activation of immune cells and triggers systemic inflammation through the peripheral circulation. The impact of GM dysbiosis extends beyond the gastrointestinal tract. Recent research indicates two-way interactions between the GM and various organs, emphasizing the idea of a “gut–organ axis”. This communication is facilitated through a range of signalling pathways and direct interactions between the host and the GM. Arrows indicate a bidirectional relationship between the gut and each organ. Parts of the figure were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/ accessed on 25 August 2023).

Any deviation from the normal composition of the GM, termed “microbial dysbiosis”, is characterised by an imbalance in the composition and/or function of the microbial ecology. Dysbiosis has been classified into numerous types or combinations of types, including (1) the loss of health-promoting microorganisms; (2) the expression of pathobionts or potentially beneficial microorganisms; and (3) the loss of overall microbial diversity (Figure 1) ^[12]. Environmental factors as well as host-related factors can influence homeostasis, such as perinatal disruption of colonization, genetics, diet, disease, and stress ^[13]. Several studies have highlighted the dysbiosis of the GM during the course of diseases such as inflammatory bowel disease (IBD), malnutrition, metabolic disorders, asthma, and neurodegenerative diseases. In most diseases, it has been reported that altered microbiota causes pathophysiologies in vital human organs; however, few studies have demonstrated the causal relationship between microbial alterations and disease phenotypes, and it remains unclear whether the altered GM contributes to a disease or simply reflects its status ^[13].

According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), prebiotics are substrates that are “selectively utilized by host microorganisms, conferring a health benefit” ^[14]. Fructo-oligosaccharides (FOS), galacto-oligosaccharides (GOS), lactulose, and inulin are the most widely recognised prebiotics, whereas β-glucans derived from various mushroom species (e.g., Pleurotus eryngii) are potential prebiotic candidates ^[15]. Recently, whole-food-based treatments have been used to modulate the GM through potential synergistic interactions between food’s various components ^[15]. Restoration of the GM in various diseases with pro/prebiotics has been postulated, but evidence for the effects of prebiotics is scarce.

2. The Gut–Brain Axis

The gut–brain axis comprises a complex physiological system that enables bidirectional communication between the gut and the host nervous system. ^[16]. This bidirectional communication within the gut–brain axis elucidates how messages from the GM influence brain function and how signals from the brain impact gastrointestinal physiology and gut microbial activity ^[17]. These bidirectional communications involve the central nervous system (CNS), intrinsic branches of the enteric nervous system (ENS), extrinsic parasympathetic and sympathetic branches of the autonomic nervous system (ANS), the hypothalamic–pituitary–adrenal axis (HPA), neuroimmune pathways (neurotransmitters, hormones, and neuropeptides), and the gut microenvironment ^[15]^[18]. The HPA axis, a component of the limbic system, is considered the central stress efferent axis that coordinates the organism’s adaptive responses to all stressors. Environmental stress and elevated systemic pro-inflammatory cytokines activate this system, which, via the secretion of the corticotropin-releasing factor from the hypothalamus, stimulates adrenocorticotropic hormone secretion from the pituitary gland, which ultimately results in cortisol release from the adrenal glands ^[6]. Thus, the combination of neural and hormonal lines of communication allows the brain to influence the activities of gut functional effector cells, including immune cells, epithelial cells, and enteric neurons ^[19]. On the other hand, these same cells are influenced by the GM, which may influence these central processes directly and indirectly via immune system activation, the production of neurotransmitters, and the production of short-chain fatty acids (SCFAs) and key dietary amino acids such as tryptophan and its metabolites ^[20]. Furthermore, the GM can act through the permeability of the gut barrier, with an increase in circulating lipopolysaccharide (LPS), modulating the levels of brain-derived neurotrophic factor and altering neuroendocrine and neural pathways.

In addition, the brain affects gut peristalsis, and sensory and secretion function, mainly via the vagus nerve. The vagus nerve, which transmits information from the luminal environment to the CNS, is the major nerve of the parasympathetic system of the ANS and a crucial modulatory constitutive direct communication pathway between the GM and the brain ^[21]. The vagus nerve consists of sensory and motor neurons and has been extensively studied for its involvement in hunger, satiety, and stress response but also for its major role in the regulation of inflammation via neuronal motor efferents ^[22].

The gut–brain axis is expected to have many effects on mood, motivation, and higher cognitive functions, in addition to ensuring that gastrointestinal homeostasis is properly maintained ^[6]. Disruption of the delicate balance between host and gut bacteria could be a contributing factor behind various diseases. The dysregulation of the gut–brain axis has been linked by numerous researchers to various immunologic, neurologic, and psychiatric disorders.

2.1. Gut Dysbiosis in Neurologic Diseases

GM dysbiosis interferes with the development of local and systemic inflammatory states, resulting in altered gut epithelial barrier integrity, allowing the release of hormones, microbial metabolites, and components by the GM that reach the brain via the vagus nerve, crossing the blood–brain barrier, and inducing neurodegenerative processes ^[23]. Moreover, dysbiosis increases the permeability of the cerebral parenchyma, which may result in neuroinflammation and dysfunctional neuronal cells. Emerging research indicates that gut dysbiosis may influence the onset and progression of a variety of neurological disorders, such as autism spectrum disorder (ASD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and schizophrenia. Table 1 provides a summary of the main dysbiotic events on the GM composition identified in neurological disorders. Subsequent sections will delve into the analysis of representative diseases and their associated dysbiotic events.

2.1.1. Dysbiosis in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a complex group of neurodevelopmental disorders characterised by aberrant social interactions and communication, repetitive and stereotyped patterns of behaviour, and abnormal sensory responses. ^[24]. According to a recent systematic literature review, the prevalence of ASD in US children ranked 1.70 and 1.85% in children aged 4 and 8 years, respectively, while the prevalence in Europe ranged between 0.38 and 1.55% ^[25]. Although genetic and environmental factors have been linked to the development of ASD, the precise etiology remains unknown. Recent research has highlighted the role of the gut–brain axis in various neuropsychiatric disorders, including autism spectrum disorder. In addition, individuals with ASD frequently experience gastrointestinal disturbances, such as constipation, diarrhoea, flatulence, increased gut permeability, and abdominal pain ^[26]^[27].

Several studies have highlighted differences in the GM composition between ASD and neurotypical children ^[28]. It should be noted, however, that among studies related to ASD, no specific microbial species has been found to be significantly different, as various factors such as diet, age, sex, population, and severity of autism should be taken into account ^[28]. Although changes in the GM composition of autistic children are not always consistent across studies, patients frequently exhibit microbial imbalances of multiple types, including higher abundances of Bacteroides, Parabacteroides, Clostridium, Faecalibacterium, and Phascolarctobacterium and a lower relative abundance of Streptococcus and Bifidobacterium ^[26]^[29].

The gastrointestinal symptoms of individuals with ASD seem to be significantly correlated with the degree of behavioural and cognitive impairment. For example, in individuals with ASD, irritability, aggressiveness, sleep disturbances, and self-injury are strongly associated with GI symptoms ^[26]^[30]. This evidence suggests that gastrointestinal abnormalities, perhaps linked to gut dysbiosis, may be associated with ASD ^[31]. Consistent with this hypothesis, a meta-analysis by Iglesias-Vázquez et al. ^[29] suggests that there is a dysbiosis in ASD children that may influence the development and severity of ASD symptomatology. More specifically, this study concluded that the microbiota of ASD individuals was mainly composed of the phyla Bacteroidetes, Firmicutes, and Actinobacteria and also showed a significantly higher abundance of the genera Bacteroides, Parabacteroides, Clostridium, Faecalibacterium, and Phascolarctobacterium and a lower percentage of Coprococcus and Bifidobacterium. Taken together, all these alterations in the GM could be associated with increased GI disturbances in individuals with ASD.

2.1.2. Dysbiosis in Parkinson’s Disease

Parkinson’s disease (PD) is the second most common degenerative disorder of the brain, affecting seven to ten million people worldwide ^[32]. PD is mainly characterised by multifactorial motor and non-motor symptoms, including resting tremor, muscular rigidity, slowness of movement, and gait abnormality, as well as cognitive disturbances, depression, mood deflection, sensory alternations, and sleep alternations ^[32]^[33]. The principal pathology of PD is characterised by the loss of dopamine-producing neurons present in a specific region of the brain, known as the substantia nigra, accompanied by the accumulation of alfa-synuclein (alfa-syn) in the form of Lewy bodies and Lewy neurites, a condition known as synucleinopathy ^[34].

Complex genetic and environmental factors are involved in the etiology of PD; however, the cause of PD remains unknown. Gastrointestinal symptoms are observed in most PD patients, including hypersalivation, dysphagia, constipation, nausea, altered bowel habits, and defecatory dysfunction ^[32]. Several studies have demonstrated GM abnormalities in patients with PD ^[35]^[36]^[37]. A meta-analysis conducted by Romano et al. ^[38] re-analysing the ten currently available 16S microbiome datasets found significant alterations in the PD-associated microbiome. More specifically, the authors concluded that enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus, emerged as the most consistent PD gut microbiome changes, suggesting that the observed dysbiosis may be a result of pro-inflammation, which could be linked to the GI symptom manifestation in PD patients ^[38]. In another study, consistent increases were principally shown in the family Verrucomicrobiaceae, genus Akkermansia, and species Akkermansia muciniphila, while health-promoting genera and butyrate producers Roseburia and Faecalibaterium were reported to decrease in PD patients ^[39]. Emerging studies have shown the correlations between GM alterations and the phenotypes of PD, including both motor and non-motor symptoms ^[40]^[41]^[42]. These alterations in the GM of patients may reveal a mechanism, as this observed dysbiosis has been associated with increased intestinal barrier permeability and subsequent gut inflammation. This hypothesis is supported by a number of studies that demonstrate that GM dysbiosis in PD is shown to be associated with the disrupted intestinal barrier, which is closely associated with gut inflammation, an established symptom in PD patients ^[43]^[44].

2.1.3. Dysbiosis in Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease defined by progressive loss of cortical, brain stem, and spinal motor neurons, resulting in weakness and wasting of the musculature ^[45]^[46]. In addition, ALS presents extra-motor features, including cognitive and behavioural disturbances ^[47]. Over 90% of ALS cases are sporadic (sALS) and of unknown cause, while the remaining 10% are familial (fALS) since they carry a mutation in one of the disease-related genes ^[47]. Mutations of superoxide dismutase 1 (SOD1), FUS RNA binding protein (FUS/TLS), C9orf72-SMCR8 complex subunit (C9orf72), and TAR DNA binding protein (TARDBP/TDP-43) are more commonly associated with ALS ^[48].

ALS etiology and pathophysiology require further elucidation, and in spite of massive efforts having been invested, there is no cure available at present, leading to death by respiratory failure within 2–5 years from symptom onset ^[49]. Recent studies demonstrate a strong pathophysiological crosstalk between the GM and ALS ^[50]. ALS pathogenesis has been linked to alterations in GM composition, impaired metabolism, an altered innate immune response, and the production of gut-derived neurotoxins by Clostridia species that induce brain damage ^[50].

Due to a number of factors, such as the small sample size, the observed heterogeneity within the study population, the various experimental procedures and data analysis, and the heterogeneity of the GM regardless of health status, the results of human studies conducted to determine the potential role of the GM in ALS patients are frequently inconclusive. Despite the contradictory results among the studies, some important findings could be observed, which include the following: (1) Differences in the GM populations between ALS patients and healthy individuals. For example, in the study of Fang et al. ^[51], which examined six ALS patients and five healthy people without ALS, the authors demonstrated significant differences in GM composition between the two groups. More specifically, in the gut of ALS patients, a reduced ratio of Firmicutes/Bacteroidetes was accompanied by a decreased abundance of butyrate-producing Oscillibacter, Anaerostipes, and Lachnospira counts and an increased abundance of glucose-metabolizing Dorea. More recently, comparing the GM of 10 ALS patients and their spouses (n = 10), it was found that the populations of the ALS patients’ GM were more diverse and deficient in Prevotella spp., suggesting that modifying the gut microbiome, such as via amelioration of Prevotella spp. deficiency, and/or altering butyrate metabolism, may have translational value for ALS treatment ^[52]. (2) GM composition alters during the course of the ALS. Gioia and colleagues ^[53] studied the GM of 50 ALS patients and 50 matched controls and demonstrated that the GM of ALS patients differed from that of controls. Also, the composition of the intestinal microbiota changed as the disease progressed, as indicated by a significant decrease in the number of operational taxonomy units observed during the follow-up. Intriguingly, an imbalance between potentially protective microbial groups, such as Bacteroidetes, and those with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria, has been observed.

Overall, these findings indicate the implication of the GM in ALS disease; however, it has been difficult to ascertain whether these changes in the GM are the cause of ALS, an aggravating factor for the disease, or the result of the disease. Additional human clinical research evidence is required in order to establish the exact role of the GM in the pathogenesis of ALS.

2.1.4. Dysbiosis in Schizophrenia

Schizophrenia is a complex, heterogeneous, neurodevelopmental disorder with deficits across many dimensions ^[54]. The expression of the underlying genetic vulnerability is shaped by a multifaceted combination of prenatal and early postnatal environmental factors ^[55]^[56]. These factors may sensitise a developing brain and its information processing ability to the subsequent accumulation of additional environmental insults, which may overwhelm compensatory capacities during adolescence and emerge as psychotic symptoms ^[57]. Subtle deficits in cognition, social communication, and functioning are often evident prior to the onset of overt psychotic symptoms ^[58], and the majority of people experience recurring psychotic relapses with variable degrees of functional impairment ^[59].

A precise integrative mechanistic understanding of the interaction of genetic and environmental processes across the neurodevelopmental trajectory in this condition remains elusive. The link between schizophrenia and the GM has garnered increasing attention in recent years. The main findings of existing studies examining the link between the GM and schizophrenia include the following:

(a) Patients with schizophrenia have a deviant GM compared to healthy controls. The diversity and composition of the GM were substantially altered in schizophrenia patients, according to these findings ^[60]^[61]. Zheng et al. ^[60] found significant alterations in beta diversity but not alpha diversity between the GM of patients and controls. In the schizophrenia group, an enhanced count of bacterial families like Prevotellaceae, Veillonellaceae, Bacteroidaceae, and Coriobacteriaceae was observed compared to healthy controls, while Ruminococcus and Roseburia abundances were significantly lower in patients with schizophrenia.

(b) Specific bacteria may function as biomarkers to differentiate patients with schizophrenia from healthy individuals ^[62]^[63]. Shen et al. identified 12 biomarkers that could be used as diagnostic factors to differentiate the schizophrenia cohort from the control cohort, including Gammaproteobacteria (at class level), Enterobacteriales (at order level), Alcaligenaceae, Enterobacteriaceae, and Lachnospiraceae (at family level), Acidaminococcus, Phascolarctobacterium, Blautia, Desulfovibrio, and Megasphaera (at genus level), and Plebeius fragilis (at species level).

(c) Differences in the GM between remission and acute schizophrenia. Pan et al. ^[63] demonstrated differences between acute and remission patients, indicating that alterations in the intestinal microbiota may influence the prognosis of the disease and suggesting the GM’s potential as a non-invasive diagnostic tool.

(d) Differences in the GM between first-episode drug-naïve and chronically medicated schizophrenia patients ^[64]. Chronically antipsychotic-treated schizophrenia patients showed lower microbial richness and diversity as compared to first-episode drug-naïve schizophrenia patients and healthy controls, suggesting that the gut microbiome may be implicated in the pathophysiology of schizophrenia via modulation of specific brain structures ^[64].

(e) The role of the gut–brain axis. The GM was found to be associated with schizophrenia via processes involved in the gut–brain axis, including immune-regulating pathways, neurotransmitter synthesis, the production of bioactive microbial metabolites, and tryptophan metabolism ^[65]. Schizophrenia-related behaviour has been observed in mice by Zheng et al. ^[60], who demonstrated that transplantation of the GM from schizophrenia patients induces schizophrenia-like behaviours in germ-free recipient rodents, suggesting that the GM can affect the brain neurochemistry associated with the onset of schizophrenia.

2.2. The Role of Prebiotics in Neurological Diseases

In recent years, different studies, including mostly in vitro and in vivo studies, and only a few human studies, have shown the beneficial effects of prebiotics on brain function ^[66]^[67]. The proposed mechanisms for prebiotic-based modulation of the GM–brain axis include the following ^[68]^[69]^[70]: (i) decreased inflammation in gut inflammatory disorders, preventing the presence of inflammatory compounds in the brain; (ii) improvement of GM composition and modulation of brain function, enhancing the composition of the GM; and (iii) influence on the production of neurochemicals. In addition, it has been suggested that, compared to probiotics, prebiotics could be advantageous due to probiotics’ inability to survive in the GI tract ^[68].

Numerous clinical studies examine the impact of probiotics and symbiotics on neurological conditions ^[71]^[72]^[73]. On the other hand, the supplementation of prebiotics to manipulate the GM as a novel treatment for neurological diseases has not been investigated, and there are only a few human studies that examine the effectiveness of prebiotics, while in ALS there have been no clinical studies (Table 2). The first study to examine the effects of prebiotics on ASD was conducted by Grimaldi et al. ^[74]. More particularly, the authors assessed the impact of a prebiotic (B-GOS^® mixture, Clasado Biosciences Ltd., Reading, UK) on GM composition and metabolic activity in 30 autistic children. According to the results, the administration of B-GOS led to modulation of the GM composition in autistic children following unrestricted diets. This modulation primarily affected bifidobacterial populations and also affected other bacterial groups, including members of the Lachnospiraceae family such as Coprococcus spp., Dorea formicigenerans, and Oribacterium spp. ^[74]. Furthermore, another study noted an amelioration of GM dysbiosis in children with ASD ^[75]. Dietary supplementation with partially hydrolysed guar gum (PHGG) in ASD children increased the relative prevalence of Acidaminococcus and Blautia, whereas the relative prevalence of Streptococcus, Odoribacter, and Eubacterium decreased. Also, prebiotic intervention decreased the behavioural irritability of ASD children ^[75]. Two studies have been conducted examining the effect of prebiotic supplementation with a simultaneous effect on GM modulation in Parkinson’s disease ^[76]^[77]. In the study of Becker et al. ^[77], an 8-week prebiotic intervention with resistant starch (RS) was conducted, enrolling 87 subjects distributed across three study arms: 32 PD patients who received RS, 30 control subjects who also received RS, and 25 PD patients who were provided with dietary instructions only. According to the results, a reduction in non-motor symptom load and a stable gut microbiome in PD patients after RS intervention were observed. In the study of Hall et al. ^[76], an open-label, non-randomised study was conducted in 10 newly diagnosed and 10 non-medicated and treated PD participants, wherein the impact of 10 days of prebiotic (bar containing resistant starch and rice brain) intervention was evaluated. The prebiotic supplementation resulted in a reduction in the relative abundance of potentially pro-inflammatory bacteria, such as Proteobacteria and Escherichia coli, while increasing the relative abundance of SCFA-producing bacteria, including Faecalibacterium prausnitzii. In addition, the unified Parkinson’s disease rating scale improved with prebiotic treatment ^[76]. The effects of prebiotic supplementation on schizophrenia were studied by Ido et al. ^[78]. More specifically, a female subject with schizophrenia was administered a prebiotic preparation of lactosucrose while keeping her medication unchanged. According to the results, after three months of lactosucrose administration, there was an improvement in psychotic symptoms, a significant decrease in the abundance of Clostridium, and an increased Bifidobacterium-to-Clostridium ratio ^[78].

More research is required to determine the effects of prebiotics in the management of neurological diseases. While there have been promising studies suggesting potential benefits, more comprehensive and long-term human research is needed to establish conclusive evidence.

Table 1. Main dysbiotic events that occur in GM during the onset and progression of neurological disorders.

Neurodegenerative Disease	Main Dysbiotic Events in GM	Reference
Autism spectrum disorder (ASD)	- Higher abundances of Bacteroides, Parabacteroides, Clostridium, Faecalibacterium, and Phascolarctobacterium and a lower relative abundance of Streptococcus and Bifidobacterium in ASD patients - Dysbiosis in ASD children may influence the development and severity of ASD symptomatology	^[15]^[26]^[29]
Parkinson’s disease (PD)	- Enrichment of the genera Lactobacillus, Akkermansia, and Bifidobacterium and depletion of bacteria belonging to the Lachnospiraceae family and the Faecalibacterium genus in PD patients	^[38]^[39]
Amyotrophic lateral sclerosis (ALS)	- Reduced ratio of Firmicutes/Bacteroidetes, decreased abundance of butyrate-producing Oscillibacter, Anaerostipes, Lachnospira counts, and Prevotella, increased abundance of glucose-metabolizing Dorea in ALS patients - GM composition alters during the course of the ALS	^[51]^[53]
Schizophrenia	- In the schizophrenia group, an enhanced count of bacterial families like Prevotellaceae, Veillonellaceae, Bacteroidaceae, and Coriobacteriaceae was observed compared to healthy controls, while Ruminococcus and Roseburia abundances were significantly lower in patients with schizophrenia - Specific bacteria may function as biomarkers to differentiate schizophrenia from healthy individuals - Differences in GM between remission and acute schizophrenia as well as between first-episode drug-naïve and chronically medicated schizophrenia patients	^[60]^[62]^[63]^[64]

Table 2. GM manipulation-based interventions with prebiotics in human health.

Disease	Study Design	Population	Prebiotic Compound	Effects on the Disease	Beneficial Effects on GM	Reference
Neurological diseases	Randomised, double-blind, placebo-controlled study	30 children diagnosed with ASD were categorised into two groups, A and B, based on their dietary habits. Group A consisted of children with unrestricted diets (n = 18), while Group B comprised those following an exclusion diet (n = 12). Subsequently, within each of these groups, children were assigned randomly to two feeding subgroups using a random number system. Group I received a placebo, while Group II was administered B-GOS^®	B-GOS^® mixture (Bimuno^®; Clasado Biosciences Ltd., Reading, UK) 1.8 g: 80% GOS content for a 6-week feeding period	Improvement in social behaviour scores	The administration of B-GOS led to modulation of the GM composition in autistic children following unrestricted diets. This modulation primarily affected bifidobacterial populations and also influenced other bacterial groups, including members of the Lachnospiraceae family such as Coprococcus spp., Dorea formicigenerans, and Oribacterium spp.	^[74]
	Cohort study	13 ASD children aged 4–9 years	Partially hydrolysed guar gum (6 g/day) for two months or longer	Decrease the behavioural irritability	The relative prevalence of Acidaminococcus and Blautia increased, whereas the relative prevalence of Streptococcus, Odoribacter, and Eubacterium decreased	^[75]
	Open-label, non-randomised study	20 participants with PD, consisting of 10 newly diagnosed, non-medicated individuals with PD and 10 individuals who were already receiving treatment for PD	Prebiotics in the form of a bar containing resistant starch, rice bran, resistant maltodextrin, and inulin for 10 days (one bar = 10 g fibre)	Unified Parkinson’s Disease Rating Scale improved with treatment	The consumption of prebiotics resulted in a reduction in the relative abundance of potentially pro-inflammatory bacteria, such as Proteobacteria and Escherichia coli, while increasing the relative abundance of bacteria known to produce SCFAs, including Faecalibacterium prausnitzii	^[76]
	Monocentric, prospective, open-label clinical trial	The study included 87 subjects distributed across three study arms: 32 PD patients who received resistant starch, 30 control subjects who also received resistant starch, and 25 PD patients who were provided with dietary instructions only	5 g of resistant starch twice per day orally over a period of 8 weeks	Reduction in non-motor symptom load in the PD patients who received resistant starch	Stabilised faecal microbial diversity	^[77]
		1 female subject with schizophrenia	A prebiotic preparation of lactosucrose (OligoOne^®) 3.0 g/day was administered, with the medication unchanged	Improvement of psychotic symptoms	After three months of lactosucrose administration, there was a significant decrease in the abundance of Clostridium and an increased Bifidobacterium to Clostridium ratio. Additionally, improvements were observed in bowel movements, and there was a reduction in constipation	^[78]
Liver diseases	Placebo-controlled, randomised pilot trial	14 individuals with liver-biopsy-confirmed NASH	The subjects were randomised to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months	Prebiotic improved liver steatosis relative to placebo and improved overall NAS score	Oligofructose supplementation led to an increase in Bifidobacterium levels, while it resulted in a reduction of bacteria belonging to Clostridium cluster XI and I	^[79]
Liver diseases	Small cohort single-centre study	Twenty-four subjects with histologically confirmed liver cirrhosis and a body mass index (BMI) of 25.78 kg/m² were compared to 29 healthy controls	In the patient group, lactitol was administered orally at a dosage of 5 g three times daily, and samples were collected after four weeks of treatment	All clinical parameters, including MELD, showed no difference between pre- and post-lactitol treatment groups	After the lactitol intervention, there was an increase in the levels of health-promoting lactic acid bacteria, such as Bifidobacterium longum, B. pseudo-catenulatum, and Lactobacillus salivarius. Additionally, there was a significant decrease in the pathogen Klebsiella pneumonia and the associated antibiotic-resistant genes and virulence factors	^[80]
Heart diseases	Randomised, placebo-controlled, double-blind cross-over trial	Untreated individuals with hypertension, being of either sex, 18–70 years of age, and having a BMI of 18.5–35 kg/m²	Participants were initially assigned to either Diet A or Diet B for a duration of 3 weeks. Diet A included HAMSAB (prebiotic acetylated and butyrylated high amylose maize starch) administered at a daily dosage of 40 g, while Diet B consisted of a daily intake of 40 g of a placebo over the same 3-week period. After a 3-week washout period, participants switched to the opposite diet arm for another 3 weeks	Reduction in ambulatory systolic blood pressure	HAMSAB intervention promoted the growth of the commensal bacteria P. distasonis and R. gauvreauii and supported the restoration of local production of SCFAs by these microbes	^[81]
Kidney diseases	Double-blind, parallel, randomised, placebo-controlled trial	20 patients with end-stage CKD undergoing haemodialysis	The participants were randomised to two groups: one received biscuits containing 20 g/d of high-amylose maize-resistant starch type 2 (HAM-RS2), an insoluble, fermentable fibre, while the other received regular wheat flour (placebo) for the first month and 25 g/d during the second month	Decrease in in systemic inflammation (serum urea, IL-6, TNFα, and malondialdehyde)	Supplementation of amylose-resistant starch, HAM-RS2, in patients with CKD led to an increase in Faecalibacterium	^[82]
	Randomised controlled clinical trial	32 patients with CKD in stages 3 and 4 were recruited and randomly assigned to intervention (n = 16) and control (n = 16) groups	Patients in intervention group received 30 mm lactulose syrup three timesa day for an 8-week period. Control group received placebo 30 mm three times a day	Creatinine significantly decreased in intervention group	Lactulose administration increase faecal Bifidobacteria and Lactobacillus counts in CKD patients	^[83]
	Randomised, double-blind, placebo-controlled, crossover study	12 patients undergoing haemodialysis	Patients were randomised to consume inulin (10 g/d for females; 15 g/d for males) or maltodextrin (6 g/d for females; 9 g/d for males) for 4 weeks, with a 4-week washout period	Inulin did not reduce faecal p-cresol or indoles, or plasma concentrations of p-cresyl sulphate or indoxyl sulphate	Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia. In addition, inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides	^[84]
	Randomised single-centre, single-blinded control trial	59 predialysis participants with CKD in stages 3 to 5 were randomised	59 participants were randomised to either the β-glucan prebiotic intervention group (13.5 g of β-glucan prebiotic fibre supplement containing 6 g of fibre, of which 3 g was β-glucan per serving) daily (n = 30) or the control group (n = 29) for 14 weeks	Supplementation of β-glucan fibre resulted in reduced plasma levels of the free fraction of colon-derived uremic toxins, without a change in kidney function over the 14-week study period	High prevalence of Bacteroides 2 in the CKD population	^[85]

References

Hou, K.; Wu, Z.-X.; Chen, X.-Y.; Wang, J.-Q.; Zhang, D.; Xiao, C.; Zhu, D.; Koya, J.B.; Wei, L.; Li, J.; et al. Microbiota in health and diseases. Signal Transduct. Target. Ther. 2022, 7, 135.
Chen, Y.; Zhou, J.; Wang, L. Role and mechanism of gut microbiota in human disease. Front. Cell. Infect. Microbiol. 2021, 11, 86.
Afzaal, M.; Saeed, F.; Shah, Y.A.; Hussain, M.; Rabail, R.; Socol, C.T.; Hassoun, A.; Pateiro, M.; Lorenzo, J.M.; Rusu, A.V. Human gut microbiota in health and disease: Unveiling the relationship. Front. Microbiol. 2022, 13, 999001.
Sender, R.; Fuchs, S.; Milo, R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016, 14, e1002533.
Matzaras, R.; Nikopoulou, A.; Protonotariou, E.; Christaki, E. Gut microbiota modulation and prevention of dysbiosis as an alternative approach to antimicrobial resistance: A narrative review. Yale J. Biol. Med. 2022, 95, 479.
Carabotti, M.; Scirocco, A.; Maselli, M.A.; Severi, C. The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. Q. Publ. Hell. Soc. Gastroenterol. 2015, 28, 203.
Van de Wouw, M.; Schellekens, H.; Dinan, T.G.; Cryan, J.F. Microbiota-gut-brain axis: Modulator of host metabolism and appetite. J. Nutr. 2017, 147, 727–745.
Auchtung, T.A.; Fofanova, T.Y.; Stewart, C.J.; Nash, A.K.; Wong, M.C.; Gesell, J.R.; Auchtung, J.M.; Ajami, N.J.; Petrosino, J.F. Investigating colonization of the healthy adult gastrointestinal tract by fungi. MSphere 2018, 3, e00092-18.
Matijašić, M.; Meštrović, T.; Čipčić Paljetak, H.; Perić, M.; Barešić, A.; Verbanac, D. Gut microbiota beyond bacteria—Mycobiome, virome, archaeome, and eukaryotic parasites in IBD. Int. J. Mol. Sci. 2020, 21, 2668.
Ahlawat, S.; Asha; Sharma, K. Gut–organ axis: A microbial outreach and networking. Lett. Appl. Microbiol. 2021, 72, 636–668.
Guo, Y.; Chen, X.; Gong, P.; Li, G.; Yao, W.; Yang, W. The Gut–Organ-Axis Concept: Advances the Application of Gut-on-Chip Technology. Int. J. Mol. Sci. 2023, 24, 4089.
Petersen, C.; Round, J.L. Defining dysbiosis and its influence on host immunity and disease. Cell. Microbiol. 2014, 16, 1024–1033.
Das, B.; Nair, G.B. Homeostasis and dysbiosis of the gut microbiome in health and disease. J. Biosci. 2019, 44, 117.
Ng, Q.X.; Loke, W.; Venkatanarayanan, N.; Lim, D.Y.; Soh, A.Y.S.; Yeo, W.S. A systematic review of the role of prebiotics and probiotics in autism spectrum disorders. Medicina 2019, 55, 129.
Saxami, G.; Mitsou, E.K.; Kerezoudi, E.N.; Mavrouli, I.; Vlassopoulou, M.; Koutrotsios, G.; Mountzouris, K.C.; Zervakis, G.I.; Kyriacou, A. In Vitro Fermentation of Edible Mushrooms: Effects on Faecal Microbiota Characteristics of Autistic and Neurotypical Children. Microorganisms 2023, 11, 414.
Sandhu, K.V.; Sherwin, E.; Schellekens, H.; Stanton, C.; Dinan, T.G.; Cryan, J.F. Feeding the microbiota-gut-brain axis: Diet, microbiome, and neuropsychiatry. Transl. Res. 2017, 179, 223–244.
Naveed, M.; Zhou, Q.-G.; Xu, C.; Taleb, A.; Meng, F.; Ahmed, B.; Zhang, Y.; Fukunaga, K.; Han, F. Gut-brain axis: A matter of concern in neuropsychiatric disorders…! Prog. Neuropsychopharmacol. Biol. Psychiatry 2021, 104, 110051.
Cryan, J.F.; O’Riordan, K.J.; Cowan, C.S.M.; Sandhu, K.V.; Bastiaanssen, T.F.S.; Boehme, M.; Codagnone, M.G.; Cussotto, S.; Fulling, C.; Golubeva, A.V.; et al. The Microbiota-Gut-Brain Axis. Physiol. Rev. 2019, 99, 1877–2013.
Breit, S.; Kupferberg, A.; Rogler, G.; Hasler, G. Vagus nerve as modulator of the brain–gut axis in psychiatric and inflammatory disorders. Front. Psychiatry 2018, 9, 44.
Miri, S.; Yeo, J.; Abubaker, S.; Hammami, R. Neuromicrobiology, an emerging neurometabolic facet of the gut microbiome? Front. Microbiol. 2023, 14, 1098412.
Yarandi, S.S.; Peterson, D.A.; Treisman, G.J.; Moran, T.H.; Pasricha, P.J. Modulatory effects of gut microbiota on the central nervous system: How gut could play a role in neuropsychiatric health and diseases. J. Neurogastroenterol. Motil. 2016, 22, 201.
Fülling, C.; Dinan, T.G.; Cryan, J.F. Gut microbe to brain signaling: What happens in vagus. Neuron 2019, 101, 998–1002.
Intili, G.; Paladino, L.; Rappa, F.; Alberti, G.; Plicato, A.; Calabrò, F.; Fucarino, A.; Cappello, F.; Bucchieri, F.; Tomasello, G. From Dysbiosis to Neurodegenerative Diseases through Different Communication Pathways: An Overview. Biology 2023, 12, 195.
Zhu, J.; Guo, M.; Yang, T.; Lai, X.; Tang, T.; Chen, J.; Li, L.; Li, T. Nutritional Status and Symptoms in Preschool Children With Autism Spectrum Disorder: A Two-Center Comparative Study in Chongqing and Hainan Province, China. Front. Pediatr. 2020, 8, 469.
Bougeard, C.; Picarel-Blanchot, F.; Schmid, R.; Campbell, R.; Buitelaar, J. Prevalence of Autism Spectrum Disorder and Co-morbidities in Children and Adolescents: A Systematic Literature Review. Front. Psychiatry 2021, 12, 744709.
Andreo-Martínez, P.; García-Martínez, N.; Sánchez-Samper, E.; González, A. An approach to gut microbiota profile in children with autism spectrum disorder. Environ. Microbiol. Rep. 2019, 12, 115–135.
Yitik Tonkaz, G.; Esin, I.S.; Turan, B.; Uslu, H.; Dursun, O.B. Determinants of Leaky Gut and Gut Microbiota Differences in Children With Autism Spectrum Disorder and Their Siblings. J. Autism Dev. Disord. 2022, 53, 2703–2716.
Alharthi, A.; Alhazmi, S.; Alburae, N.; Bahieldin, A. The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder. Int. J. Mol. Sci. 2022, 23, 1363.
Iglesias-Vázquez, L.; Van Ginkel Riba, G.; Arija, V.; Canals, J. Composition of Gut Microbiota in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Nutrients 2020, 12, 792.
Chakraborty, P.; Carpenter, K.L.H.; Major, S.; Deaver, M.; Vermeer, S.; Herold, B.; Franz, L.; Howard, J.; Dawson, G. Gastrointestinal problems are associated with increased repetitive behaviors but not social communication difficulties in young children with autism spectrum disorders. Autism 2021, 25, 405–415.
Cryan, J.F.; Dinan, T.G. Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nat. Rev. Neurosci. 2012, 13, 701–712.
Faruqui, N.A.; Prium, D.H.; Mowna, S.A.; Rahaman, T.I.; Dutta, A.R.; Akter, M.F. Identification of Common Molecular Signatures Shared between Alzheimer’s and Parkinson’s Diseases and Therapeutic Agents Exploration: An Integrated Genomics Approach. bioRxiv 2021.
Ma, Q.; Xing, C.; Long, W.; Wang, H.Y.; Liu, Q.; Wang, R.-F. Impact of microbiota on central nervous system and neurological diseases: The gut-brain axis. J. Neuroinflammation 2019, 16, 53.
Stopińska, K.; Radziwoń-Zaleska, M.; Domitrz, I. The Microbiota-Gut-Brain Axis as a Key to Neuropsychiatric Disorders: A Mini Review. J. Clin. Med. 2021, 10, 4640.
Elfil, M.; Kamel, S.; Kandil, M.; Koo, B.B.; Schaefer, S.M. Implications of the gut microbiome in Parkinson’s disease. Mov. Disord. 2020, 35, 921–933.
Grochowska, M.; Laskus, T.; Radkowski, M. Gut microbiota in neurological disorders. Arch. Immunol. Ther. Exp. 2019, 67, 375–383.
Lin, A.; Zheng, W.; He, Y.; Tang, W.; Wei, X.; He, R.; Huang, W.; Su, Y.; Huang, Y.; Zhou, H.; et al. Gut microbiota in patients with Parkinson’s disease in southern China. Park. Relat. Disord. 2018, 53, 82–88.
Romano, S.; Savva, G.; Bedarf, J.; Charles, I.; Hildebrand, F.; Narbad, A. Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation. npj Park. Dis. 2021, 7, 27.
Guo, T.; Chen, L. Gut microbiota and inflammation in Parkinson’s disease: Pathogenetic and therapeutic insights. Eur. J. Inflamm. 2022, 20, 1721727X221083763.
Lin, C.-H.; Chen, C.-C.; Chiang, H.-L.; Liou, J.-M.; Chang, C.-M.; Lu, T.-P.; Chuang, E.Y.; Tai, Y.-C.; Cheng, C.; Lin, H.-Y. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson’s disease. J. Neuroinflammation 2019, 16, 129.
Scheperjans, F.; Aho, V.; Pereira, P.A.; Koskinen, K.; Paulin, L.; Pekkonen, E.; Haapaniemi, E.; Kaakkola, S.; Eerola-Rautio, J.; Pohja, M. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov. Disord. 2015, 30, 350–358.
Vascellari, S.; Melis, M.; Palmas, V.; Pisanu, S.; Serra, A.; Perra, D.; Santoru, M.L.; Oppo, V.; Cusano, R.; Uva, P. Clinical phenotypes of Parkinson’s disease associate with distinct gut microbiota and metabolome enterotypes. Biomolecules 2021, 11, 144.
Hashish, S.; Salama, M. The Role of an Altered Gut Microbiome in Parkinson’s Disease: A Narrative Review. Appl. Microbiol. 2023, 3, 429–447.
Yang, D.; Zhao, D.; Ali Shah, S.Z.; Wu, W.; Lai, M.; Zhang, X.; Li, J.; Guan, Z.; Zhao, H.; Li, W. The role of the gut microbiota in the pathogenesis of Parkinson’s disease. Front. Neurol. 2019, 10, 1155.
Boddy, S.L.; Giovannelli, I.; Sassani, M.; Cooper-Knock, J.; Snyder, M.P.; Segal, E.; Elinav, E.; Barker, L.A.; Shaw, P.J.; McDermott, C.J. The gut microbiome: A key player in the complexity of amyotrophic lateral sclerosis (ALS). BMC Med. 2021, 19, 13.
Gotkine, M.; Kviatcovsky, D.; Elinav, E. Amyotrophic lateral sclerosis and intestinal microbiota—Toward establishing cause and effect. Gut Microbes 2020, 11, 1833–1841.
McCombe, P.A.; Henderson, R.D.; Lee, A.; Lee, J.D.; Woodruff, T.M.; Restuadi, R.; McRae, A.; Wray, N.R.; Ngo, S.; Steyn, F.J. Gut microbiota in ALS: Possible role in pathogenesis? Expert Rev. Neurother. 2019, 19, 785–805.
Zeng, Q.; Shen, J.; Chen, K.; Zhou, J.; Liao, Q.; Lu, K.; Yuan, J.; Bi, F. The alteration of gut microbiome and metabolism in amyotrophic lateral sclerosis patients. Sci. Rep. 2020, 10, 12998.
Maskovic, J.; Ilic, A.; Zugic, V.; Stevic, Z.; Stjepanovic, M.I. What is the right moment for noninvasive ventilation in amyotrophic lateral sclerosis? Arch. Med. Sci. 2023, 19, 337.
Chidambaram, S.B.; Essa, M.M.; Rathipriya, A.; Bishir, M.; Ray, B.; Mahalakshmi, A.M.; Tousif, A.; Sakharkar, M.K.; Kashyap, R.S.; Friedland, R.P. Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle. Pharmacol. Ther. 2022, 231, 107988.
Fang, X.; Wang, X.; Yang, S.; Meng, F.; Wang, X.; Wei, H.; Chen, T. Evaluation of the microbial diversity in amyotrophic lateral sclerosis using high-throughput sequencing. Front. Microbiol. 2016, 7, 1479.
Hertzberg, V.S.; Singh, H.; Fournier, C.N.; Moustafa, A.; Polak, M.; Kuelbs, C.A.; Torralba, M.G.; Tansey, M.G.; Nelson, K.E.; Glass, J.D. Gut microbiome differences between amyotrophic lateral sclerosis patients and spouse controls. Amyotroph. Lateral Scler. Front. Degener. 2022, 23, 91–99.
Di Gioia, D.; Bozzi Cionci, N.; Baffoni, L.; Amoruso, A.; Pane, M.; Mogna, L.; Gaggìa, F.; Lucenti, M.A.; Bersano, E.; Cantello, R. A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis. BMC Med. 2020, 18, 153.
Insel, T.R. Rethinking schizophrenia. Nature 2010, 468, 187–193.
Howes, O.D.; Murray, R.M. Schizophrenia: An integrated sociodevelopmental-cognitive model. Lancet 2014, 383, 1677–1687.
Howes, O.D.; McCutcheon, R.; Owen, M.J.; Murray, R.M. The role of genes, stress, and dopamine in the development of schizophrenia. Biol. Psychiatry 2017, 81, 9–20.
Kahn, R.; Sommer, I. The neurobiology and treatment of first-episode schizophrenia. Mol. Psychiatry 2015, 20, 84–97.
Kahn, R.S.; Keefe, R.S. Schizophrenia is a cognitive illness: Time for a change in focus. JAMA Psychiatry 2013, 70, 1107–1112.
Menezes, N.; Arenovich, T.; Zipursky, R. A systematic review of longitudinal outcome studies of first-episode psychosis. Psychol. Med. 2006, 36, 1349–1362.
Zheng, P.; Zeng, B.; Liu, M.; Chen, J.; Pan, J.; Han, Y.; Liu, Y.; Cheng, K.; Zhou, C.; Wang, H. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Sci. Adv. 2019, 5, eaau8317.
Gokulakrishnan, K.; Nikhil, J.; Viswanath, B.; Thirumoorthy, C.; Narasimhan, S.; Devarajan, B.; Joseph, E.; David, A.K.D.; Sharma, S.; Vasudevan, K. Comparison of gut microbiome profile in patients with schizophrenia and healthy controls-A plausible non-invasive biomarker? J. Psychiatr. Res. 2023, 162, 140–149.
Shen, Y.; Xu, J.; Li, Z.; Huang, Y.; Yuan, Y.; Wang, J.; Zhang, M.; Hu, S.; Liang, Y. Analysis of gut microbiota diversity and auxiliary diagnosis as a biomarker in patients with schizophrenia: A cross-sectional study. Schizophr. Res. 2018, 197, 470–477.
Pan, R.; Zhang, X.; Gao, J.; Yi, W.; Wei, Q.; Su, H. Analysis of the diversity of intestinal microbiome and its potential value as a biomarker in patients with schizophrenia: A cohort study. Psychiatry Res. 2020, 291, 113260.
Ma, X.; Asif, H.; Dai, L.; He, Y.; Zheng, W.; Wang, D.; Ren, H.; Tang, J.; Li, C.; Jin, K. Alteration of the gut microbiome in first-episode drug-naïve and chronic medicated schizophrenia correlate with regional brain volumes. J. Psychiatr. Res. 2020, 123, 136–144.
Yang, C.; Lin, X.; Wang, X.; Liu, H.; Huang, J.; Wang, S. The schizophrenia and gut microbiota: A bibliometric and visual analysis. Front. Psychiatry 2022, 13, 1022472.
Kao, A.C.C.; Harty, S.; Burnet, P.W.J. Chapter Two—The Influence of Prebiotics on Neurobiology and Behavior. In Gut Microbiome and Behavior; Cryan, J.F., Clarke, G., Eds.; International Review of Neurobiology; Academic Press: Cambridge, MA, USA, 2016; Volume 131, pp. 21–48.
He, Q.; Si, C.; Sun, Z.; Chen, Y.; Zhang, X. The intervention of prebiotics on depression via the Gut–Brain axis. Molecules 2022, 27, 3671.
Liu, X.; Cao, S.; Zhang, X. Modulation of gut microbiota–brain axis by probiotics, prebiotics, and diet. J. Agric. Food Chem. 2015, 63, 7885–7895.
Franco-Robles, E.; Ramírez-Emiliano, J.; López-Briones, J.S.; Balcón-Pacheco, C.D. Prebiotics and the Modulation on the Microbiota-GALT-Brain Axis. In Prebiotics and Probiotics-Potential Benefits in Nutrition and Health; IntechOpen: London, UK, 2019.
Chakrabarti, A.; Geurts, L.; Hoyles, L.; Iozzo, P.; Kraneveld, A.D.; La Fata, G.; Miani, M.; Patterson, E.; Pot, B.; Shortt, C. The microbiota–gut–brain axis: Pathways to better brain health. Perspectives on what we know, what we need to investigate and how to put knowledge into practice. Cell. Mol. Life Sci. 2022, 79, 80.
Lee, S.H.; Ahmad, S.R.; Lim, Y.C.; Zulkipli, I.N. The use of probiotic therapy in metabolic and neurological diseases. Front. Nutr. 2022, 9, 887019.
Sharma, V.; Kaur, S. The Effect of Probiotic Intervention in Ameliorating the Altered Central Nervous System Functions in Neurological Disorders: A Review. Open Microbiol. J. 2020, 14, 18–29.
Babu, C.S.; Chethan, N.; Rao, B.S.; Bhat, A.; Bipul, R.; Tousif, A.; Mahadevan, M.; Sathiya, S.; Manivasagam, T.; Thenmozhi, A.J. Probiotics, prebiotics, and synbiotics on neurological disorders: Relevance to Huntington’s disease. In Food for Huntington’s Disease; Nova Science Publishers, Inc.: Hauppauge, NY, USA, 2018; pp. 105–140.
Grimaldi, R.; Gibson, G.R.; Vulevic, J.; Giallourou, N.; Castro-Mejía, J.L.; Hansen, L.H.; Leigh Gibson, E.; Nielsen, D.S.; Costabile, A. A prebiotic intervention study in children with autism spectrum disorders (ASDs). Microbiome 2018, 6, 133.
Inoue, R.; Sakaue, Y.; Kawada, Y.; Tamaki, R.; Yasukawa, Z.; Ozeki, M.; Ueba, S.; Sawai, C.; Nonomura, K.; Tsukahara, T.; et al. Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder. J. Clin. Biochem. Nutr. 2019, 64, 217–223.
Hall, D.; Voigt-Zuwala, R.; Jungles, T.; Hamaker, B.; Engen, P.; Shaikh, M.; Raeisi, S.; Green, S.; Naqib, A.; Forsyth, C.; et al. An open label, non-randomized study assessing a prebiotic fiber intervention in a small cohort of Parkinson’s disease participants. Nat. Commun. 2023, 14, 926.
Becker, A.; Schmartz, G.; Gröger, L.; Grammes, N.; Galata, V.; Philippeit, H.; Weiland, J.; Ludwig, N.; Meese, E.; Tierling, S.; et al. Effects of Resistant Starch on Symptoms, Fecal Markers and Gut Microbiota in Parkinson’s Disease—The RESISTA-PD Trial. Genom. Proteom. Bioinform. 2021, 20, 274–287.
Ido, Y.; Nagamine, T.; Okamura, T.; Tasaki, M.; Fukuo, K. Prebiotic lactosucrose may improve not only constipation but also psychotic symptoms of Schizophrenia. Int. Med. J. 2017, 24, 305–306.
Bomhof, M.; Parnell, J.; Ramay, H.; Crotty, P.; Rioux, K.; Probert, C.; Jayakumar, S.; Raman, M.; Reimer, R. Histological improvement of non-alcoholic steatohepatitis with a prebiotic: A pilot clinical trial. Eur. J. Nutr. 2019, 58, 1735–1745.
Lu, H.; Chen, L.; Pan, X.; Yao, Y.; Huan, Z.; Zhu, X.; Lou, X.; Zhu, C.; Wang, J.; Li, L.; et al. Lactitol Supplementation Modulates Intestinal Microbiome in Liver Cirrhotic Patients. Front. Med. 2021, 8, 762930.
Jama, H.; Rhys-Jones, D.; Nakai, M.; Yao, C.; Climie, R.; Sata, Y.; Anderson, D.; Creek, D.; Head, G.; Kaye, D.; et al. Prebiotic intervention with HAMSAB in untreated essential hypertensive patients assessed in a phase II randomized trial. Nat. Cardiovasc. Res. 2023, 2, 35–43.
Laffin, M.; Park, H.; Laffin, L.; Madsen, K.; Kafil, H.; Abedi, B.; Shiralizadeh, S.; Vaziri, N. Amylose resistant starch (HAM-RS2) supplementation increases the proportion of Faecalibacterium bacteria in end-stage renal disease patients: Microbial analysis from a randomized placebo-controlled trial. Hemodial. Int. 2019, 23, 343–347.
Tayebi-Khosroshahi, H.; Habibzadeh, A.; Niknafs, B.; Ghotaslou, R.; Yeganeh Sefidan, F.; Ghojazadeh, M.; Moghaddaszadeh, M.; Parkhide, S. The effect of lactulose supplementation on fecal microflora of patients with chronic kidney disease; a randomized clinical trial. J. Ren. Inj. Prev. 2016, 5, 162–167.
Biruete, A.; Cross, T.-W.; Allen, J.; Kistler, B.; Loor, H.; Evenepoel, P.; Fahey, G.; Bauer, L.; Swanson, K.; Wilund, K. Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study. J. Ren. Nutr. 2021, 31, 512–522.
Ebrahim, Z.; Proost, S.; Tito Tadeo, R.; Raes, J.; Glorieux, G.; Moosa, R.; Blaauw, R. The Effect of ß-Glucan Prebiotic on Kidney Function, Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial. Nutrients 2022, 14, 805.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Microbiology

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Georgia Saxami

Evangelia N. Kerezoudi

Christos Eliopoulos

Dimitrios Arapoglou

Adamantini Kyriacou

View Times: 245

Update Date: 19 Oct 2023

Table of Contents

Video Upload Options

Confirm