Table 3.

Summary of the main findings from the included studies focused on the evaluation of microbiota modulation in the CRSwNP treatment.

Ref.	Population (P)	Intervention (I)	Comparison (C)	Outcome (O)
[96]	CRSwNP patients underwent bilateral FESS	Clarithromycin + MFNS Duration: Three or six months	MFNS	No significant changes in the nasal microbiota: The proportion of clarithromycin-resistant strains remained constant throughout the antibiotic treatment. Some clinical benefits were observed in the antibiotic-treated groups: lower CT scores and eosinophil cationic protein (ECP) levels than the control group.
[70]	CRSwNP patients underwent ESS	Clarithromycin + MFNS Duration: Eight weeks	MFNS	Adding clarithromycin to MFNS was associated with a significant eradication in biofilm formation (six of 12 biofilm-positive samples before surgery turned negative) when compared to MFNS alone (one of 11 biofilm-positive samples). It was not demonstrated that combined therapy was superior in improving tomography (CT) and symptom (SNOT-20) scores.
[95]	Post-surgical CRSwNP patients with patent maxillary antrostomy	Treatment of nasal saline irrigation or intranasal corticosteroid spray of any type * CRSwNP patients who used saline irrigation also used topical corticosteroids (spray or irrigation)	DCs	No significant changes in the nasal microbiota associated with saline irrigation or intranasal corticosteroid spray.
[105]	CRSwNP and CRSsNP patients for whom ESS was indicated	Doxycycline or prednisone Duration: Seven days * All patients continued with daily topical corticosteroids nasal sprays and regular sinonasal saline lavage	Placebo	In individual patients, doxycycline was associated with an increase in RA of Corynebacterium and Haemophilus compared to prednisone and untreated controls.
[107]	CRSwNP and CRSsNP patients underwent ESS	Manuka honey (MH) with augmented methylglyoxal (MXO) sinonasal rinses Duration: Two weeks and ten days of placebo tablets or culture-directed oral antibiotic tablets (control group)	Placebo (saline sinonasal rinses)	50% of patients had a reduction in standard semiquantitative bacterial culture rate (mainly about S. aureus) after the MH + MXO treatment. A statistically significant reduction in LKS (Lund–Kennedy score) outcome was also observed after the treatment.
[113]	CRSwNP and CRSsNP patients with previous ESS	Topical administration of live Lactococcus lactis W126 Duration: Two weeks * All patients continued with saline irrigation	No placebo control was included	Treatment was associated with a reduced abundance of multiple species of Staphylococcus, Peptostreptococcae, and Enterobacialles, as well as an increased abundance of Dolosigranulum pigrum. The response pattern showed progressive improvement during the treatment and post-treatment (SNOT-22 scores, nasal congestion, post-nasal drip, and need to blow nose).
[89]	CRSwNP, CRSnNP patients, and DCs	Oral antibiotics treatment within three months before sampling	No antibiotics treatment	Alpha diversity (Shannon and Simpson indexes) was significantly lower in patients who had taken antibiotics than in patients who had not. Streptococcaceae, Lachnospiraceae, and Neisseriaceae were significantly decreased in patients who had taken antibiotics compared to patients who had not.
[122] *	CRSwNP patients underwent FESS	Intranasal gel with bacteriophage mixture (Otofag) Duration: Ten weeks	Placebo	The total number of bacteria significantly decreased in the experimental group compared to the placebo group. In detail, a significant decrease in the number of Streptococci and Enterobacteriaceae was observed in the experimental group. The decrease in cytokines in the nasal lavage fluid (IL-8) and blood serum (IL-1B) was proved by the total number of microorganisms and by the concentration of Enterobacteriaceae and Staphylococci.
[83]	CRSwNP patients	Prednisone + amoxicillin–clavulanate or prednisone alone Duration: Prednisone for three weeks and amoxicillin–clavulanate for two weeks * All patients were concurrent to their baseline intranasal saline irrigation and topical corticosteroid	DCs	Non-significant changes in the nasal microbiota. Micrococcus was isolated before both treatments but not post-treatment. After three months from treatment, an increase in the prevalence of Corynebacterium was observed in the group treated with prednisone and amoxicillin–clavulanate, as well as in Gram-negative (Pseudomonas) and Staphylococcus genera in the group treated only with prednisone. Both treatments showed significant short-term (after one month from treatment) improvement (SNOT-22), but not in the long term (after three months).

CRSwNP, chronic rhinosinusitis with nasal polyps; CRSsNP, chronic rhinosinusitis without nasal polyps; DC, disease control patient; ESS, endoscopic sinus surgery; FESS, functional ESS; MFNS, mometasone furoate nasal spray; CT, computed tomography; SNOT, Sinonasal Outcome Test. *: Additional information. Reported clinical benefits are shown in italics.