Table 2.

Summary of studies investigating the role of microbiome-derived metabolites in HSCT setting in human.

Metabolites	Study Design	Results	References
Fiber-Derived Metabolites—Short-Chain Fatty Acids
Butyrate	1325 allo-HSCT adult patients	Post-transplant enterococcal domination and loss of Clostridiales were associated with a reduction in butyrate in patients developing GvHD.	[12]
Butyrate, propionate, acetate	35 allo-HSCT adult aGvHD patients	Butyrate, propionate and acetate levels were lower in patients experiencing GvHD 2–3 compared to the control. Butyrate was low even in patents with GvHD 1.	[18]
Butyrate, propionate, acetate, formate	42 allo-HSCT pediatric patients	Butyrate, propionate, acetate decrease within the first 14 days after HSCT and are lower in patients developing GvHD. Formate is a possible marker for the Enterobacteriaceae family. Expression of butyrate transporters in GvHD is altered. Greater number of days of antibiotic was associated with lower levels of butyrate and propionate.	[19]
Butyrate, propionate, hexanoate, isobutyrate	10 allo-HSCT adult cGvHD patients	Plasma concentration of SCFAs reflects fecal content. Patents developing cGvHD present lower plasma concentration of butyrate, propionate, hexanoate, isobutyrate.	[20]
Butyrate	44 allo-HSCT adult patients	Butyrate levels were correlated with Shannon index and were low in patients experiencing bloodstream infections within 30 days after HSCT.	[21]
Butyrate, propionate, acetate, desaminotyrosine	360 allo-HSCT adult patients	Butyrate-producing bacteria and fecal SCFAs were associated with a protection from viral lower respiratory tract infections	[22]
Butyrate	99 allo-HSCT adult patients	Oral supplementation with resistant starch and commercially available prebiotic mixture, GFO, resulted in higher post-HSCT butyrate-producing bacteria and a maintained or increased fecal butyrate concentration.	[23]
Butyrate, propionate, acetate	20 allo-HSCT pediatric patients	Enteral nutrition resulted in higher fecal concentration of butyrate, propionate and acetate.	[24]
Amino Acid-Derived Metabolites
Tryptophan-derived AhR ligand
3-IS	131 allo-HSCT adult patients	Lower 3-IS urinary levels are associated with higher transplant-related mortality and worse outcome. 3-IS urinary levels are correlated with GM diversity and with a higher presence of Eubacterium rectale and Ruminococcaceae.	[25]
3-IS	13 allo-HSCT adult patients receiving FMT	FMT results in higher 3-IS urinary levels.	[26]
Indoxyl sulfate	Two cohort of 43 and 56 allo-HSCT adult patients	Tryptophan-derived AhR ligand 3-indoxyl sulfate was involved in the GvHD-related metabolic alterations.	[27]
Tyrosine-derived metabolites
Tyrosine	86 allo-HSCT adult patients	In patients who develop aGvHD tyrosine metabolism was found to be altered. Other microbiome-derived metabolites (tryptophan, lysine, phenylalanine and secondary bile acids) were altered.	[28]
Riboflavin (Vitamin B2)-Derived Metabolites
Riboflavin	121 allo-HSCT adult patients receiving CBT	Patients with post-HSCT MAIT cells reconstitution had a GM with higher expression of genes involved in the riboflavin synthesis pathway.	[29]
Polyamines and Breath Metabolites
N-acetylputrescine, agmatine	184 allo-HSCT adult patients	Salivary metabolic profile of HSCT patients with and without severe oral mucositis (grade 0–1 vs. 3–4) was found to be different. Metabolites such as urea, 5-aminovalerate, N-acetylputrescine and agmatine, also show differences between the pre-transplant and the time of mucositis onset.	[30]
2-propanol, acetaldehyde, dimethyl sulfide, isoprene, and 1-decene	19 allo-HSCT adult patients	Comparing patients with and without GI GvHD, the former show modification in the levels of volatile organic compounds, namely 2-propanol, acetaldehyde, dimethyl sulfide, isoprene, and 1-decene.	[31]