Table 1 Impact of TiO₂ particles on the intestinal microbiota^a

 Waller et al., 2016 [80]

Model human colon reactor: bacteria isolated from a fecal sample from a human donor, grown in aerobic condition

5 days, three times a days. TiO₂ diluted in a fluid simulating digested food entering the large intestine. Exposure under flow, in the dark

P25 (Evonik, 21 nm, anatase/rutile) and commercially available TiO₂, similar to food grade TiO₂ (122 nm)

Sonication for 30 min in water

Decrease of bacteria number. Inhibition of the bacterial shift observed in control condition (Proteobacteria to Firmicutes phyla). Decreased colonic pH. Mild effect on microbial stability (microbial community hydrophobicity, electrophoretic mobility). Food-grade TiO₂ particles show greater effect.

 Dudefroi et al., 2017 [79]

MET-1 bacterial community (33 bacterial strains), grown in anaerobic condition

100–250 ppm. Incubation in the dark under agitation.

Two different E171 and NM105 TiO₂-NP (21 nm, anatase/rutile)

Suspension in distilled water, no sonication

No impact on gas production by bacteria. Minor effect on fatty acids profiles. Limited effect on bacterial communities: decrease of Bacteroides ovatus, increase of Clostridium cocleatum.

 Radziwill-Bienkowska et al., 2018 [78]

Eight Gram-positive/Gram-negative bacterial strains

32–320 μg/mL, 15 min to 24 h, in the dark, under agitation ot nor, depending on the strain.

E171 and NM105 TiO₂-NP (22 nm, anatase/rutile)

Probe sonication in 0.05% water/BSA, 27 min

Adsorption of TiO₂ on the surface of bacteria, with accumulation in 7% of E. coli, as measured by nano-SIMS. Alteration of growth profiles and moderate reduction of cell cultivability. Morphological damage on a small number of bacteria.

 Chen et al., 2017 [82]

Mice, oral gavage

2,5 mg/kg b.w./day, once a day for 7 days

TiO₂-NPs, anatase, 17 nm (TEM)

Suspension in water, bath sonication for 15 min

No change of gut microbiota composition.

 Li et al., 2018 [61]

Mice, oral gavage

100 mg/kg b.w./day, once a day for 28 days

TiO₂-NPs, anatase (20 nm, DLS) and rutile (16 nm, DLS)

Suspension in distilled water, no sonication

No decrease of gut microbiota diversity, but its structure is shifted: Proteobacteria increased by rutile TiO₂, Prevotella decreased by anatase and rutile TiO₂, Rhodococcus increased by rutile TiO₂, Bacteroides increased by anatase TiO₂.

 Pinget et al., 2019 [133]

Mice, drinking water

2, 10, 50 mg TiO₂/kg b.w./day for 21 days

E171

Suspension in drinking water

Limited impact on bacterial diversity, richness, evenness or Faith’s diversity in fecal samples in the colon. Impact at the genus level in the colon, depending on the dose. No impact in the small intestine. Significant modulation of commensal bacterial activity at 50 mg/kg b.w./day. Increased biofilm formation of E. coli, E. faecalis and commensal bacteria exposed to 2, 10 and 50 μg/mL for 24 h or 72 h, in vitro.

 Cao et al., 2020 [81]

Mice, exposure in food pellets

0.1 wt% in food pellets for 8 weeks

E171 or TiO₂-NPs, anatase, 33 nm (TEM)

Mixed with food, either low-fat or high-fat diet

Microbiota dysbiosis: increased abundance of Firmicutes and decreased abundance of Bacteroidetes; decreased abundance of Bifidobacterium and Lactobacillus genera, concurrent with decreased level of short-chain fatty acids. Associated with colon inflammation. More intense in obese mice and in mice treated with TiO₂-NPs compared to E171. Microbiota transplant experiment suggests that inflammation is directly linked with dysbiosis.