Table 2.

Impact of Drugs of Abuse on Microbiome, Metabolite, and Immune Markers. This table outlines the current literature on the effects of alcohol, opioids, stimulants, psychedelics, THC, and CBD on the microbiome

Species	Sample Site	Drug	ROA	Δ Microbiome	Δ Metabolites	Δ Immune response	Citation
Rat	Intestine Liver	Alcohol	Oral	Testing of LGG supplement	-	LGG supplement reduced liver health and IP to near control levels ↑ Oxidative stress ↑ Carbonyl ↑ Nitrotyrosine	(Forsyth et al. 2009)
Mouse	Small Intestine Large Intestine	Alcohol	Oral	↓ Lactobacillus ↓ Lactococcus ↓ Leuconostoc ↓ Pediococcus ↑ Bacteroidetes ↑ Verrucomicrobia ↑ Akkermansia	-	↓ Reg3b ↓ Reg3g ↓ Defensin 5 ⍺	(Yan et al. 2011)
Mouse	Feces	Alcohol	Oral	↓ Firmicutes ↓ Bacteriodetes ↑ Proteobacteria ↑ Actinobacteria (*4)	↑ Endotoxins	Endotoxemia reduced by Lactobacillus rhamnosus (LGG) probiotic ↑ TNF-alpha	(Bull-Otterson et al. 2013)
Mouse	Feces	Alcohol	Oral	↓ Lactobacillus ↑ Akkermansia Muciniphilia	-	-	(Hartmann et al. 2013)
Mouse	Feces	Alcohol	Intragastric	↓ Lactobacillus	↓ LCFA	↓ Genes involved in the biosynthesis of saturated fatty	(Chen et al. 2014)
Mouse	Feces	Alcohol	CIE	↑ Alistipes ↓ Clostridium IV ↓ Clostridium XIVb ↓ Coprococcus ↓ Dorea ↓ Alpha Diversity (CIE) ↑ Akkermansia (CIE)	Decrease in SCFA producers	Similar reductions in Dorea and Coprococcus in chronic social stress models have been correlated to increases in proinflammatory cytokines IL-6 and MCP-1 (Bailey et al. 2011)	(Peterson et al. 2017)
Mouse	Feces Colon	Alcohol	Oral	↓ Bacteroidetes ↓ Firmicutes ↑ Proteobacteria	-	↑ IL-1β	(Kang et al. 2017)
Rat	Jejunum Colon	Alcohol	Oral	↑ Bacteroidetes ↓ Firmicutes ↑ Proteobacteria	↑ Blood Endotoxin	↑ Amino Acid metabolism (arginine and proline)	(Fan et al. 2018)
Mouse	Feces Liver Colon	Alcohol	Oral	↑ Bacteroidetes ↑ Verrucomicrobia ↑ Firmicutes ↓ Ruminococcaceae ↑ Odoribacter	No significant change in SCFA	↑ Serotonin ↑ Taurine ↑ Bile acid level	(Wang et al. 2018b)
Rat	Feces	Alcohol	Oral	↓ Diversity ↓ Lactobacillus ↓ Peptostreptococcaceae ↓ Turicibacter ↑ Parabacteroides ↑ Barnesiellaceae ↑ Bacteroides	-	-	(Kosnicki et al. 2019)
Mouse	Feces	Alcohol	Intragastric	↓ Bacteroidetes ↑ Firmicutes ↓Muribaculum intestinales	-	-	(Lee et al. 2020)
Human	Jejunum	Alcohol	Oral				(Bode et al. 1984)
Human	Feces	Alcohol	Oral	↓ Bifidobacteria ↓ Enterococci ↓ Lactobacilli	-	-	(Kirpich et al. 2008)
Human	Feces	Alcohol*(1)	See below	↓ Bacteroidetes ↑ Proteobacteria ↑ Fusobacteria	-	-	(Chen et al. 2011)
Human	Colon	Alcohol	Oral	↓ Bacteroidetes ↑ Proteobacteria	↑ Endotoxin	↑ Cytokines ↑ Oxidase	(Mutlu et al. 2012)
Human	Urine	Alcohol	Oral	-	↑ Blood LPS	↑ TNF⍺ ↑ IL-6	(Leclercq et al. 2012)
Human	Feces, Urine	Alcohol	Oral	↓ Lactobacillus ↓ Bifidobacterium (reversed during withdrawal) ↓ Ruminococcae (*5) ↑ Lachnospiraceae (*5) ↓ F. Prausnitzii (*5)	MCFA lower in control and withdrawal, Phenol higher in AUD (*2)	Drawing connection of leaky gut (IP) to dysbiosis	(Leclercq et al. 2014)
Human	Feces	Alcohol	Oral	↑ Bacteroidetes ↓ Firmicutes	-	-	(Volpe et al. 2014)
Human	Feces	Alcohol	Oral	-	↑ Tetradecane ↓ Fatty alcohols ↓ Propionate ↓ Isobutyrate ↓ Caryophyllene ↓ Camphene ↓ Dimethyl-disulfide ↓ Dimethyl-trisulfide	-	(Couch et al. 2015)
Human	Feces	Alcohol	Oral	↑ Proteobacteria ↓ Faecalibacterium ↑ Sutterella ↑ Holdemania ↑ Clostridium	↓ Butyric acid	-	(Bjorkhaug et al. 2019)
Mouse	Feces	Cocaine	IP	↓ Mucispirillum ↓ Ruminococcaceae ↓ Lachnospiracea ↓ Pseudoflavonifractor ↓ Butrycicoccus	-	↑ NF-κB ↑ IL-1β ↑ IL-18 ↑ CCL-2 ↑ CCL-7 ↑ CXCL-10 ↑CCL-11	(Chivero, et al. 2019)
Rat	Feces	Cocaine	Volatized	↓ Alpha Diversity ↓ Beta Diversity	↓ Aromatic amino acid decarboxylase gene	-	(Scorza et al. 2019)
Human	Feces	Cocaine	Active Users	↑ Bacteroidetes ↓ Firmicutes	No Change in Blood LPS	↑ Interferon-γ	(Volpe et al. 2014)
Rat	Feces	Methamphetamine	IP	↑ Diversity ↓ Acidaminococcaceae ↓ Phascolarctobacterium ↑ Ruminococcaceae	↓ Propionate	-	(Ning et al. 2017)
Human	Rectal swab	Methamphetamine	Active users	↑ Finegoldia ↑ Parvimonas ↑ Peptoniphilus ↑ Porphyromonas ↓ Butyricicoccus ↓ Faecalibacterium	-	-	(Cook et al. 2019)
Human	Feces	Heroin Methamphetamine Ephedrine	Active Users	↑ Thauera, ↑ Paracoccus ↑ Prevotella	Not examined	-	(Xu et al. 2017)
Human	Feces	Opioids	Active Users	↑ Alpha Diversity	-	-	(Vincent et al. 2016)
Human	Feces	Opioids	Active Users	↓Bacteriodacea ↓Clostridiales XI ↓Ruminococcaceae	↑ Amino Acid metabolism ↑ Degradation of BCAA	↑Endotoxemia ↑ IL-6	(Acharya et al. 2017)
Human	Feces	Opioids	Active Users	↑ Bifidobacterium ↑ Prevotella	-	-	(Barengolts et al. 2018)
Mouse	Blood Lavage	Morphine	Passive Exposure model of sepsis	↑Staphylococcus ↑Enterococcus		↑IL-17 vial TLR2 ↑Intestinal inflammation	(Meng et al. 2015)
Mouse	Feces	Morphine	Passive Exposure	↓ Bacteroidetes ↑ Firmicutes	↓ Primary Bile Acids ↓ Secondary Bile Acids	↑IL-17 ↓IL-10	(Banerjee et al. 2016)
Mouse	Feces	Morphine	Passive Exposure	↑ Enterococcus Faecalis	↓ Bile Acids (DCA) ↑ Saturated Fats ↑ Phospytidylethanolamine (PE)	-	(Wang et al. 2018a)
Mouse	Feces	Morphine	IP (intermittant and sustained)	↑ Ruminococcus (int) ↓ Lactobacillus (int) ↑ Clostridium (sust.) ↑ Rikenellaceae (sust.)	-	-	(Lee et al. 2018a)
Mouse	Feces	Oxycodone	IVSA				(Hakimian et al. 2019)
Non Human Primate	Feces	Morphine	Passive	↑ Methanobacteriaceae ↓ Streptococcaceae ↓ Pasturellaceae	↓ Primary Bile Acids ↑ Secondary Bile Acids	-	(Sindberg et al. 2019)
Rats	Caecum	Nicotine	Oral	↓ Bifidobacterium	↓ Acetic acid ↓ Propionic acid ↓ Butyric acid ↓ Valeric acid	-	(Tomoda et al. 2011)
Mice	Large intestine	Nicotine	Oral	↑ Clostridium clostridiforme ↓ Lactoccoci ↓ Ruminococcus ↓ Enterobacteriaceace (Relative abundances)	-	↓ Intestinal inflammatory response ↓ Activation of nuclear factor-κβ	(Wang et al. 2012)
Mice	Colon, ileum	Nicotine	Oral	↑ Lachnospiraeae (colon)	-	↑ Cxcl2 (ileum) ↓ IFN-γ (ileum) ↑ IL-6 (colon) ↓ TGF-β (colon)	(Allais et al. 2016)
Human	Feces	Nicotine	Oral	↑ Prevotella ↑ Bacteroides	-	-	(Benjamin et al. 2012)
Human	Feces	Nicotine	Oral	↓ Firmicutes ↑ Bacteroidetes ↑ Proteobacteria ↓ Actinobacteria	-	-	(Biedermann et al. 2013)
Human	Upper intestinal tract	Nicotine	Oral	↑ Alpha diversity ↑ Beta diversity ↑ D. invisus ↑ M. micronuciforms	-	-	(Vogtmann et al. 2015)
Human	Mouth	Nicotine	Oral	↓ Proteobacteria ↓ Capnocytophaga ↓ Peptostreptococcus ↓ Leptotrichia ↑ Atopobium ↑ Streptococcus	-	-	(Wu et al. 2016)
Human	Feces	Nicotine	Oral Gut	↓ Shannon diversity (Fecal) ↑ Prevotella ↓ Bacteroides	-	-	(Stewart et al. 2018)
Human	Feces	Nicotine	Oral	↑ Bacteroidetes ↓ Firmicutes ↓ Proteobacteria	-	-	(Lee et al. 2018b)
Human	Upper intestine	Nicotine	Oral	↑ Firmicutes ↑ Rothia ↓ Prevotella ↓ Neisseria ↓ Diversity (relative abundance)	-	-	(Shanahan et al. 2018)
Human	Ileum	None (testing Chron’s disease (CD))	NA	↓ F.Prausnitzii associated with higher CD		↓ IL-12 ↓ IFNɣ ↑ IL-10 Colitis Dysbiosis mediated with F. Prausnitzii supplement	(Sokol et al. 2008)
Mouse	Feces	Cannabis	Oral	↑ Akkermansia ↑ Firmicutes:Bacterioides		THC blocked weight gain from high fat diet	(Cluny et al. 2015)
Human	-	Cannabis	-	-	-	Highly palatable food increased endogenous cannabinoids was associated with hedonic eating	(Monteleonei et al. 2012)
Rat	-	Cannabis	-	-	-	Fasting ↑ anandamide	(Gomez et al. 2002)