Table 2.

Assessment of research and clinical trials that might modify the gut microbiome’s composition.

Microorganism		Target Disease and Mechanism	Ref
Probiotics
Clinical Trials	L. rhamnosus TCELL-1	Assessing the Efficacy of L. Rhamnosus TCELL-1 in the Treatment of Colorectal Cancer. Phase 2 clinical trials (NCT05570942) (https://classic.clinicaltrials.gov/ct2/show/NCT05570942, last accessed on 25 June 2024)
	BIO-25 (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasein, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus lactis, Lactobacillus rhamnosus, and Streptococcus thermophilus)	Evaluate the therapeutic impact of the multispecies probiotic combination “BIO-25” in patients with irritable bowel syndrome (IBS) who have diarrhoea (IBS-D). Phase 4 clinical trials (NCT01667627) (https://classic.clinicaltrials.gov/ct2/show/results/NCT01667627, last accessed on 25 June 2024)
	Lactobacillus rhamnosus, Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus gasseri, Lactobacillus plantarum, Bifidobacterium lactis, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium longum, Bifidobacterium infantis.	Effect of Probiotic Supplementation on the Immune System in Patients with Ulcerative Colitis in Amman. Phase 3 clinical trials (NCT04223479) (https://classic.clinicaltrials.gov/ct2/show/NCT04223479, last accessed on 20 July 2024) This study aims to analyse the potential negative impacts of microorganisms on the immune system, particularly the inflammatory response. It is crucial to note that in immunocompromised individuals, the use of probiotics may carry significant risks, including the potential for infections if bacteria translocate into sterile areas, or if the introduction of probiotics disrupts the existing gut microbiota balance.
	Hafnia alvei HA4597 TM	The Impact of Hafnia Alvei on Weight Loss and Glycaemic Control After Bariatric Surgery. Clinical Portuguese trials (https://classic.clinicaltrials.gov/ct2/show/NCT05170867, accessed on 25 June 2024)
Metabolic Diseases	Lactobacillus plantarum	Decrease in body fat via breaking down lipids by oxidation.	[84]
	Lactobacillus paracasei, Bifidobacterium breve, and Lactobacillus rhamnosus or mixture	Decreased blood levels of lipopolysaccharide (LPS) resulted in reduced triacylglycerol concentration in the liver.	[85]
	Mixture of Lactobacilli, Streptococcus, and Bifidobacteria	Less weight and fat mass gain in High Fat Diet with probiotics.	[86]
	Bacteroides thetaiotaomicron	Reduction in total adipose tissue and rise in body mass.	[87]
	Bifidobacterium lactis LMG P-28149, and Lactobacillus rhamnosus LMG S-28148	Addressing obesity and insulin resistance by promoting the growth of Akkermansia muciniphila and Rikenellaceae. Increasing the expression of PPARγ and lipoprotein lipase. Improving the body’s response to insulin and increasing the efficiency of triglyceride elimination Reducing the abundance of Lactobacillaceae.	[88]
	Bifidobacterium longum PI10 and Ligilactobacillus salivarius PI2	Obesity: Increasing the expression of GLP1 and IL-10.	[89]
Obesity	Lactobacillus plantarum NK3 and Bifidobacterium longum NK49	Enhancing the intestinal barrier to address obesity and osteoporosis. Inhibiting the synthesis of lipopolysaccharide (LPS). Suppressing the production of TNF-α by the downregulation of NF-κB signalling.	[90]
	Lactobacillus reuteri LR6	Protein–energy malnutrition leads to an increase in Bifidobacteria, Firmicutes, and Lactobacilli.	[91]
Diabetes	Akkermansia muciniphila	Enhancement in insulin sensitivity and metabolic function leads to a reduction in inflammation and body fat accumulation.	[92,93,94]
	Ruminococcaceae sp. Lachnospiraceae sp.	It reduces weight gain and shows beneficial effects on insulin, fasting blood glucose, inflammatory markers, leptin, and chemerin levels. Moreover, dietary therapy may alter the function and composition of microbes, leading to an increase in two butyrate-producing families.	[95]
	Lactobacillus plantarum T3 AFB1	Decreased blood glucose levels, decreased expression of SGLT-1 and GLUT-2, decreased intestinal permeability. Probiotics engage in competitive consumption of glucose.	[96]
	Lactobacillus fermentum MCC2760	Enhancing the integrity of the intestinal barrier. Increasing the expression of GLUT4, GLP1, and ZO-1.	[97]
Gut- Brain Axis	Lactobacillus plantarum ATCC 8014	Reduced levels of Aβ in the hippocampus improved cognitive decline and preserved the integrity and adaptability of neurons.	[98]
	Lactobacillus reuteri	Autism spectrum disorders alter social and repetitive behaviours, decrease the expression of GABA receptors, and increase the expression of oxytocin in the hypothalamus.	[99]
	Bifidobacteria, Lactobacillus, Laccoccus and yeast. (Patent no. ZL2015104679586)	Depression can be improved by reducing depressive behaviours, decreasing neuronal cell injury, lowering Bax and cleaved caspase-3 levels, and increasing p-AKT and Bcl-2 levels through activation of the AKT signalling pathway.	[100]
	L. brevis DSM 27961, L. acidophilus DSM 32241, L. helveticus DSM 32242, L. paracasei DSM 32243, L. plantarum DSM 32244, B. lactis DSM 32246, B. lactis DSM 32247, S. thermophilus DSM 32245	Orally administering the treatment improved glucose uptake by restoring the levels of GLUT1 and GLUT3, and IGF receptor β in the brain. This was accompanied by reduced phosphorylation of AMPK and Akt. The memory of the mice also improved due to a decrease in phosphorylated tau aggregates, an increase in glycated haemoglobin, and an accumulation of advanced glycation end products.	[101]
	Bifidobacterium longum (NK46)	Oral dosing enhanced the gut microbiota composition, decreased blood and faecal LPS levels, elevated in the colon the quantity of tight junction proteins, and decreased the production of TNF-α and the activation of NF-κB. In addition, it decreased cognitive decline, β/γ-secretase activity, amyloid beta buildup, and caspase-3 expression in the hippocampus of mice.	[102]
	Clostridium butyricum	The treatment successfully reversed the GM deficit and increased the butyrate levels. It inhibited the buildup of Aβ, cognitive decline, the release of TNF-α and IL-1β, and microglia activation.	[103]
	Lactobacillus lactis strain carrying one plasmid (pExu)	Improved memory, lowered levels of Aβ peptides, regulated the ubiquitin–proteasome system and autophagy, and decreased neuronal inflammation and oxidative processes.	[104]
IBS/IBD	Bifidobacterium longum 35624	Irritable Bowel Syndrome (IBS). Enhanced bowel movement patterns, reduced sensitivity to internal organs, increased healing of the mucous membrane. Increased lysozyme production and increased stem niche factors. WNT3A and TGF- are two molecules.	[105]
	Limosilactobacillus fermentum KBL374	Inflammatory Bowel Disease (IBD). An increase in colon length, a decrease in inflammatory cytokines, an increase in body weight, and a decrease in leukocyte infiltration. Modulating immune responses, modifying gut microbiota, increasing gut barrier function.	[106]
IBS/IBD	Lactobacillus johnsonii, and Lactobacillus reuteri	Enhancing the process of tetrathionate metabolism. Reducing the presence of Yersinia enterocolitica.	[107,108]
	Lactobacillus paracasei	Colitis accompanied with a metabolic condition Manufacturing palmitoylethanolamide with the purpose of preserving intestinal functionality.	[109]
Gut-Heart Axis	Lactobacillus casei	Hypertension is associated with an increase in the abundance of Akkermansia and Lactobacillus. Reducing the ratio of Firmicutes to Bacteroidetes and ACE (angiotensin-converting enzyme) expression.	[39,110]
	Bifidobacterium breve CECT7263 and Lactobacillus fermentum CECT5716	Enhancing the abundance of microorganisms associated with butyrate production. Increasing the concentration of butyrate in the plasma. Minimising the formation of lipopolysaccharide (LPS).	[111]
	Lactobacillus fermentum CECT5716, Lactobacillus coryniformis CECT5711 (K8), and Lactobacillus gasseri CECT5714 (LC9)	Decrease NOX activity and mRNA expression of NOX-1 and NOX-4 in spontaneously hypertensive rats	[112]
	L. reuteri V3401	Obese persons aged 18 to 65 years with metabolic syndrome have a decreased risk of cardiovascular disease (CVD) and have lower levels of inflammatory biomarkers, including TNF-α, IL-6, IL-8, and soluble intercellular adhesion molecule-1. However, even though several studies have shown that probiotics may reduce the production of proinflammatory cytokines	[113]
Liver	Bifidobacterium breve ATCC15700	Alcoholic liver disease: Decreased endotoxemia, preserved immunological balance, reduced liver damage, increased tight junction proteins Enhance intestinal barrier function and modulate gut microbiota.	[114]
Cancer	L. plantarum YYC-3	CRC (colorectal cancer) is associated with the development of colon tumours and mucosal damage, as well as a decrease in inflammatory cytokines and the VEGF-MMP2/9 signalling pathway. Immunomodulation, changes in the composition of the gut microbiota, and the release of metabolites into the body.	[115]
	Lactobacillus reuteri	Melanoma Enhancing the effectiveness of immune checkpoint inhibitors (ICIs) to improve ICI response rates and patient survival. Produces indole-3-aldehyde to activate CD8+ T cells	[116]
	Bacillus subtilis ZK3814	Eliminates S. aureus, suppressed production of Agr-regulated virulence factors ZK3814	[117]
Chronic Kidney Disease	Limosilactobacillus fermentum JL-3	A 31.3% decrease in serum uric acid levels and a decrease in oxidative stress markers are characteristics of hyperuricemia. Facilitate the breakdown of uric acid and maintain the balance of gut microbes.	[118]
	L. casei 01	Kidney stones: Reduces the formation of renal calculi. Breaks down and makes use of oxalate.	[119]
	L. fermentum, L. plantarum, and B. lactis, or L. acidophilus, B. bifidum, and B. longum	Reduced the levels of microorganisms that cause inflammation and faecal zonulin, while increasing the levels of kynurenine in the blood.	[120]
	Streptococcus thermophilus KB 19, Lactobacillus acidophilus KB 27, and Bifidobacterium longum KB 31	Improvement in the standard of living. There is a decreasing trend in the levels of serum indoxyl glucuronide and C-reactive protein.	[121]
Prebiotic
Obesity	Fermentable carbohydrate inulin	The concentration of cells that generate the hormone peptide YY (PYY) rose 87%. PYY helps decrease hunger, lower food consumption, and prevent obesity caused by diet.	[122]
	Inulin	It enhances the abundance of Bifidobacterium and reduces the ratio of Firmicutes to Bacteroidetes. SCFA may function as a scavenger of reactive oxygen species (ROS). In addition, it has the ability to regulate reactions to harmful bacterial attacks (LPS) and safeguard the gut from inflammatory processes. This is likely achieved by enhancing the body’s defences against reactive oxygen species (ROS) by activating colonic mucosal detoxification enzymes (GSTs). Consequently, inulin helps restore the levels of crucial proteins involved in the functioning of the intestinal smooth muscle.	[123]
	Maize starch dextrin and Lentil	Primary use in the therapy of obesity. Enhancing the abundance of Actinobacteria and Bacteroidetes. Reducing the abundance of Firmicutes.	[124]
	Chicory oligofructose	This therapy’s main purpose is to treat obesity. It involves increasing the levels of Bifidobacterium and Collinsella.	[125]
	Amylosucrase-modified chestnut starch	Primary use in the treatment of obesity. Enhancing the activity of the short-chain fatty acid (SCFA)–GPR43 signalling pathway.	[126]
	Fuji FF	Obesity. Increasing acetic, propionic, and butyric acid production [75].	[127]
Obesity	Acorn and sago polysaccharides	Primary use in the treatment of obesity and type 2 diabetes mellitus. Decreasing intestinal permeability and signs of inflammation in the mucosal lining.	[128]
	Galactooligosaccharides	Primary use in the treatment of obesity and type 2 diabetes mellitus. Enhancing the expression of GLP1. Decreasing faecal bile acid excretion.	[129]
Diabetes	Resistant dextrin from wheat and corn starch	The primary use of this medication is for treating type 2 diabetes mellitus. Enhancing the levels of Akkermansia and Prevotella bacteria. Increasing the activity of the IRS1-Akt-GLUT2 and SIRT1-AMPK-PPARα-CPR1α pathways.	[130]
	Isomaltodextrin	Insulin resistance. Enhancing the synthesis of acetic and butyric acids. Enhancing the integrity of the intestinal barrier. Lowering the concentration of endotoxins in the bloodstream.	[131]
Dyslipidemia	Whole garlic	Dyslipidemia treatment Increasing Lachnospiraceae decreasing Prevotella.	[132]
	Fucoidan and Galactooligosaccharides	Treating dyslipidemia involves enhancing the abundance of Bacteroidetes and Proteobacteria and promoting in Lactobacillus casei the activity of bile salt hydrolase. Reduce the abundance of Actinobacteria and Firmicutes.	[133]
	Long-chain inulin	Managing hypertension. Reducing the concentrations of acetate and propionate in faeces, as well as lowering the level of TMAO in the bloodstream.	[134]
	Glycolipids from tilapia heads	Colitis is accompanied by a metabolic disorder, such as increasing Akkermansia, Allobaculum, Bifidobacterium, Coprococcus, Oscillospira, and Prevotellaceae.	[135]
Gut- Brain Axis	Xylooligosaccharides	The intervention effectively reduced changes in the gut microbiota and improved cognitive function. It also reduced inflammatory responses and improved the integrity of the tight junction barrier in both the hippocampus and intestine.	[136]
	Fructooligosaccharides	The pathological changes and cognitive deficits were improved, and the levels of synapsin I and postsynaptic density protein 95, and the level of phosphorylated c-Jun N-terminal kinase decreased. In addition, the FOS administration restored the modified GM density.	[137]
Synbiotics
	Bifidobacterium and galacto-oligosaccharides	Decreased inflammation and enhanced integrity of the intestinal barrier.	[138]
	A. muciniphila +inulin	Improve glucose levels.	[139]
	Lactobacillus plantarum C29-fermented soybean (DW2009)	The administration of DW2009 increased blood BDNF (brain-derived neurotrophic factor) levels, potentially leading to considerable improvements in cognitive and memory skills.	[137]
Chronic Kidney Diseases	Lactobacillus acidophilus and Bifidobacterium lactis + prebiotic (inulin)	Enhance digestive system symptoms. Decreasing trend in plasma C-reactive protein levels.	[33]
	Lactobacillus, Bifidobacteria and Streptococcus genera + prebiotic (inulin, fructooligosaccarides, and galacto-oligosaccarides	During the ongoing procedure, the main focus is on measuring the amount of indoxyl-sulfate, which is a crucial consequence. Secondary outcomes include the measurement of p-cresyl sulphate, LPS, TMAO, inflammation, and oxidative stress indicators, as well as the assessment of renal function and quality of life.	[140]
	Lactobacillus acidophilus and Bifidobacterium lactis + prebiotic (inulin)	CKD: Increases Bifidobacterial counts in faecal samples Reduction of Lactobacilli counts in faecal samples. Improve gastrointestinal symptoms. Slowing of progression of kidney disease.	[141]
	Lactobacillus plantarum, Lactobacillus casei subsp. rhamnosus, Lactobacillus gasseri, Bifidobacterium infantis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus salivarius Lactobacillus sporogenes, and Streptococcus thermophilus +, prebiotic (inulin and tapioca-resistant starch)	Decrease Plasma p-cresol concentration.	[142]
	Lactobacillus casei strain Shirota and Bifidobacterium breve strain Yakult + prebiotic (galacto-oligosaccharides)	Decrease p-Cresol. Normalisation of bowel habits. Decrease blood urea nitrogen levels.	[142]
	Lactobacillus acidophilus and Bifidobacterium lactis + prebiotic (inulin)	Enhance digestive system symptoms. Decreasing trend in plasma C-reactive protein levels.	[33]
Obesity	Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium plus omega-3 fatty acids	Showing a beneficial combined effect in reducing liver fat buildup and lipid accumulation compared to using probiotics alone.	[143]
	Bacillus licheniformis plus xylo-oligosaccharides	Indicating a beneficial combined impact on enhancing body weight increase and lipid metabolism. Reducing the abundance of Desulfovibrionaceae and Ruminococcaceae.	[144]
	Lactobacillus plantarum PMO 08 plus chia seeds	Unveiling a beneficial synergistic impact on enhancing obesity. Enhancing the abundance of Lactobacillus plantarum.	[145]
	Bifidobacterium lactis, Lactobacillus paracasei DSM 4633, plus oat b-glucan	Elevating concentrations of acetate, propionate, and butyrate in the faeces. Reducing the amount of bile acid reservoirs.	[146]
	Lactobacillus paracasei HII01 plus xylo-oligosaccharides	Suppressing metabolic endotoxemia. Reducing the ratio of Firmicutes to Bacteroidetes and the presence of Enterobacteriaceae.	[147]
NAFLD	Lactobacillus paracasei N1115 plus fructo-oligosaccharides	Reducing the synthesis of lipopolysaccharides (LPS). Suppressing the expression of TLR4 and NF-κB. Boosting the functionality of the p38 MAPK pathway and elevating the levels of occludin 1 and claudin 1 expression.	[148]
	Bifidobacterium bifidum V, Lactobacillus plantarum X plus Salvia miltiorrhiza polysaccharide	Reducing liver fat accumulation and enhancing insulin sensitivity. Reducing the number of lipopolysaccharides (LPS).	[149]
	Clostridium butyricum plus corn bran	Gastrointestinal dysfunction accompanied by metabolic disease. Enhances the proliferation of bacteria that generate acetate and the synthesis of acetate and isovalerate, reducing the levels of pathogens.	[150]
Postbiotics
	Peptidoglycan: L. acidophilus	Anti-inflammatory impact: lowering COX-2 levels and elevation of iNOS are associated with increased insulin sensitivity and glucose intolerance. Suppression of IL-12 production via the interaction of NOD2 and IRF4	[77]
	Teichoic acids: L. plantarum L. paracasei L. rhamnosus	Immunomodulatory action. Anti-obesogenic and anti-inflammatory effect. Inhibition of JNK, ERK, and p38 kinase phosphorylation. Improvement of phosphor-p38-AMPK levels and a reduction in NF-κB.	[151]
	Cell-Free Supernatants: Lactobacillus strains like L. acidophilus, L. casei, L. reuteri, L. lactis B. longum, Saccharomyces species like S. boulardii	Antioxidant activity, anti-inflammatory effect, anti-obesogenic effect, and IR reduction. Reduction in IL-6, TNF-α, and IL-1β expression. ROS and RNS scavenging properties. Scavenging free-radical DPPH. Inhibition of linoleic acid peroxidation. Decrease in TNF-α secretion and rise in IL-10 discharge. Reduction in the production of NO, COX-2, and Hsp70. Hepatic FGF21 up-regulation. FGF21–adiponectin signalling.	[152]
	Exopolysaccharides: Bacillus sp., L. delbrueckii, L. plantarum	Antioxidant effect, insulin resistance and type 2 diabetes regulation, anti-adipogenesis activity, hyperglycemia, and dyslipidemia improvement. Delay of atherosclerosis development inhibition of cholesterol absorption enhancement of immune response vs. pathogen ROS and RNS scavenging properties. AS160-mediated pathway. AMPK/PI3K/Akt pathway. Regulation of SCD1 (stearoyl-CoA desaturase 1), ACC (acetylCoA carboxylase), SREBP-1 (sterol regulatory element-binding protein), and FAS (fatty acid synthase). Reduction in VLDL, LDL, and triglyceride levels and increase in HDL.	[153]
	Extracellular Vesicles: A. muciniphila, Propionibacterium freudenreichii	The substance has anti-obesogenic and anti-inflammatory effects, reducing fat accumulation and modulating the NF-κB pathway. It also exhibits anti-inflammatory and antioxidant actions, prevents the invasion of colon cancer cells, shows antibacterial activity, promotes intestinal barrier health, and reverses impaired intestinal peristalsis induced by stress. Additionally, it prevents the invasion of entero invasive E. coli strains into enterocytes in vitro, improves the absorptive surface of the intestine, reduces intestinal pathogens in lambs, and aids in wound healing.	[154]
	Short chain fatty acids (butyric, propionic, and acetic acids): Lactobacillus spp.	To mitigate the risk of inflammatory diseases, such as obesity, diabetes type 2, or other ailments, it is important to increase energy consumption and promote the oxidation of fatty acids. This can be achieved by modulating the PGC-1α pathway through the activation of AMPK and the inhibition of HDACi (histone deacetylase inhibitors). Additionally, down-regulating PPARγ can also be beneficial. These compounds serve as an energy source, possess immunosuppressive properties, aid in energy harvesting and reduction of fat deposition, inhibit cholesterol synthesis, promote ulcerative colitis regression, block atherosclerosis, and improve insulin sensitivity, leading to a ‘statin-like effect’. Increase insulin secretion without impairing pancreatic beta cells. Metabolic disorder: Increasing Lachnospiraceae and Proteobacteria. Decreasing Clostridiaceae. NAFLD: Increasing Blautia, Christensenellaceae, and Lactobacillus. Increasing ZO-1 expression. Decreasing the levels of endotoxin.	[64]
	Enzymes: Lactococcus sp., Lactococcus lactis, S. thermophilus, L. casei, L. fermentum, B. adolescentis, B. longum, B. infantis, B. breve	This substance acts as an antioxidant and reduces inflammation in the intestines. It achieves this by scavenging free radicals through the action of catalase (CAT), glutathione peroxidase (GPx), NADH oxidase, and superoxide dismutase (SOD). These enzymes convert free radicals into oxygen (O2) and hydrogen peroxide (H2O2). Antioxidant activity. Possible alleviation of symptoms associated with Crohn’s disease; manipulation of gut microbiota; experimentation conducted on mice; conducted in laboratory settings; demonstrated protection against pathogens such as Giardia lamblia.	[25]
	Bacteriocins: L. plantarum	Anti-bacterial, anti-inflammatory, anti-obesogenic, reduce diabetes. Function on cytoplasmic membranes via pores creation. Reduction in TNF-α and IL-6 concentration. Stimulate reductions in weight gain and food intake. Decrease in PAI-1.	[155]