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.	[75]
	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	[76]
	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	[77]
	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	[78]
		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	[79]
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	[80]
	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	[81]
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	[82]
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	[83]
	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	[84]
	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	[85]
	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	[86]