Table 2.

List of main studies in animals associating antibiotics exposure and obesity

Research/Year	Type of mice Used	Antibiotic Treatment	Main findings	Remarks
Backhed et al. 2007 [87]	GF mice	Western diet during 6–10 weeks of life	✓ ↓ metabolic endotoxemia
Cani et al. 2008 [88]	ob/ob mice	Ampicillin 1 g/L during the first 6 weeks of life	✓ ↑ weight gain	✓ Alterations in the gut microbiota control metabolic endotoxemia and inflammation, by means of ↑ intestinal permeability.
Cho et al. 2012 [85]	C57BL/6J mice	I) Sub-therapeutic doses of antibiotics at weaning (age 3 weeks) through life II) Control group (no antibiotics administered)	Compared to the control group, the group with antibiotics administered had: ✓ ↑ 3% body fat ✓ ↑ GIP ✓ ↑ F/B ratio	✓ Administration of sub-therapeutic antibiotic therapy resulted in alterations in the gut microbiome and ↑ adiposity in mice.
Murphy et al. 2013 [89]	BL6 mice	Vancomycin 2 mg/d, high fed diet during the first 7 weeks of life	↓ weight gain ↓ fasting plasma glucose.
Cox et al. 2014 [86]	Experiment 1, 2, 3: C57BL/6J mice Experiment 4: GF Swiss Webster mice	Experiment. 1: I) Antibiotic treatment with LDP at birth or age 4 weeks and lasting throughout life II) Control group with no antibiotics administered Experiment 2: I) LDP lifelong with a high-fat diet at 17 weeks II)4 groups—all combinations with and without LDP and/ or HFD Experiment 3: I) LDP during first 4 weeks, first 8 weeks or lifelong with a HFD at 6 week II) Control group with no antibiotics administered Experiment 4: I) Transferring antibiotic-treated gut microbiota to GF mice II) Control group with no antibiotics administered	✓ Experiment 1: ↑ weight if LDP administered at birth rather than at age 4 week, with ↑ effect on male mice. ✓ Experiment 2: ↑ fat mass in both male and female mice Experiment 3: ↑ total, lean and fat mass in all groups, with ↑ effect on female mice Experiment 4: ↑ total and fat mass in recipients of gut microbiome from LDP mice.	✓ LDP exposure from birth and in early life may result in alterations in metabolism in mice and lead to ↑↑ adiposity. ✓ LDP ↑↑ the effect of HFD on the occurrence of obesity. ✓ The obese phenotype due to LDP-induced microbiome changes is transferrable.
Mahana et al. 2016 [90]	BL6 mice	Penicillin G 6.8 mg/L during the first 1–14 days of gestation	✓ ↑ weight and fat mass ✓ ↑ insulin resistance as well as NAFLD score.
Rodrigues et al. 2017 [91]	GF Swiss Webster mice	Ampicillin 1 g/l, Metronidazole 1 g/L, Neomycin 1 g/L, Vancomycin 0.5 g/L or all of them	✓ ↓ FPG	✓ ↑ Akkermansia muciniphila after Vancomycin administration
Li et al. 2017 [92]	C57BL/6 mice	I) Florfenicol II) Azithromycin III) Control group with no antibiotics administered	✓ ↑↑ F/B ratio in the two antibiotics groups. ✓ ↓↓ Rikenella in the azithromycin treated group.	✓ ↓↓ richness and diversity of microbiota in the two antibiotics groups. ✓ ↑↑ adipogenesis in the antibiotics groups.
Zarrinpar et al. 2018 [93]	Ob/ob mice DIO mice	Norfloxacin and Ampicillin for 2 weeks	✓ DIO mice exhibited ↓metabolic endotoxemia ✓ ↓ LPS levels

DIO diet-induced obesity, F/B ratio Firmicutes to Bacteroidetes ratio, FPG fasting plasma glucose, GF germ free, GIP glucose-dependent insulinotropic peptide, HFD high-fat diet, LDP low-dose penicillin, LPS lipopolysaccharide, NAFLD non-alcoholic fatty liver disease