Table 1.

Studies from different geographical locations indicating microbiota composition of the respiratory and its variation during different clinical conditions

Primary Location	Study	Remark	Ref
Asia
China	16S rDNA analysis of 83 (AN), 60 (NP), & 97 (OP) samples of 98 healthy children (≤12 years of age).	Moraxella, Staphylococcus, Corynebacterium, Streptococcus, and Dolosigranulum (AN/NP).	[67]
		Streptococcus, Prevotella, Neisseria, Veillonella, Rothia, Leptotrichia, and Haemophilus (OP).
	High throughput gene sequencing was used to evaluate BALF samples of normal and IPF patients.	Healthy individuals were showing the dominance of Sutterella, Coprococcus, Parasutterella, Paludibacter and Dorea.	[68]
		IPF samples were showing the dominance of Streptococcus (23.0% of total reads), followed by Pseudobutyrivibrio, Anaerorhabdus, Campylobacter, and Blautia.
	Respiratory samples from 171 healthy children and 76 children having pneumonia were analyzed for the presence of microbes.	The Prevotella and Streptococcus were found with healthy subjects, while Staphylococcus spp. and M. pneumoniae were predominant in the patient group.	[69]
	Sputum microbiota of tuberculosis patients (25 new, 30 recurrent, 20 with treatment failure) and 20 healthy controls were analyzed through 16s RNA sequencing.	Tuberculosis patients were primarily showing Firmicutes, while Bacteriodetes was found with healthy controls. Tuberculosis patients were showing Streptococcus, Gramulicatella and Pseudomonas, while Catonella and Coprococcus were abundant in healthy controls.	[70]
	Sputum and respiratory secretions from 31 tuberculosis (TB) and 24 healthy controls were analyzed by 16S rRNA.	Some species like Actinomyces, Granulicatella, Prevotella, Streptococcus, and Veillonella were abundant in both groups. The Anoxybacillus, Acinetobacter, Abiotrophia, Klebsiella, Pilibacter, Paucisalibacillus, and Rothia were higher in TB patients, while Campylobacter, Fusobacterium, Haemophilus, Neisseria, Porphyromonas, Parvimonas, and TM7_genera_incertae_sedis were lower in TB patients than control.	[71]
	Upper respiratory tract microbiota of H1N1 influenza virus-infected patients were analyzed through 16s rDNA analysis.	Proteobacteria was abundant while Actinobacteria, Bacteroidetes, Candidate division TM7, Firmicutes, Fusobacteria and SR1 were reduced in H1N1 patients samples. At genera level, Ochrobactrum, Brevundimonas, Caulobacter, Aquabacterium and Serratia were increased whereas Actinomyces, Acinetobacter, Haemophilus, Neisseria, Prevotella, Porphyromonas, Streptococcus, and Veillonella decreased in H1N1 samples.	[72]
Hong Kong	Sputum microbiota was analyzed by 16s rRNA in 22 TB patients and 14 control.	Controls were showing an abundance of Firmicutes while Proteobacteria and Bacteroidetes were overrepresented in the TB group.	[73]
		The core TB sputum microbiota was made of Actinomyces, Fusobacterium, Leptotrichia, Prevotella, Streptococcus, and Veillonella while Mogibacterium, Moryella and Oribacterium were also present. Unclassified Lactobacillales was overrepresented in the control group.
Singapore	Twenty-four genetically related healthy pairs (n=48) were divided into young (≤40 years) and old (≥60 years). The sputum sample of participants was collected and analyzed for microbiota composition using 16s rRNA.	Old subjects group was having an abundance of Firmicutes and relatively less abundance of Proteobacteria. Ageing is linked with augmented Firmicutes and reduced Proteobacteria in the healthy Asian cohort’s airway microbiota. Haemophilus and Lautropia were abundant in young. Firmicutes (Gemella) were related to young group lung function, while Fusobacteria and Leptotrichia were linked to elder’s arterial stiffness.	[74]
Korea	Microbiota analysis of 27 BAL fluid samples from patients undergoing diagnostic bronchoscopy using conventional microbiology media and identification through MALDI-TOF MS. In addition, 16S rRNA NGS was performed for comparison.	BAL samples showed the highest culture of Streptococcus spp. and Neisseria spp. Actinomyces and Veillonella spp. were the most common anaerobes. Other bacteria like Prevotella spp., Staphylococcus spp., Clostridium spp., and Bifidobacterium spp. were also present.	[75]
Iran	Respiratory microbiota of 3-6 years old healthy children was determined through culture and 16s rRNA.	Actinobacteria (4%), Firmicutes (74%), and Proteobacteria (22%) were most common. At genera level Staphylococci, Streptococci, Enterobacteriaceae spp. and A. baumannii were common.	[76]
India	Sputum microbiota of TB was analyzed using 16S rRNA and compared with healthy controls.	In healthy controls, Gammaproteobacteria (22%), Streptococcus (20.5%), Neisseria (16.8%) and Haemophilus (15.4%). Actinobacillus were present.	[77]
		Firmicutes and Actinobacteria were abundant in TB patient’s samples with the dominance of Streptococcus, Neisseria and Veillonella.
North America
Canada	Microbiota of URT among 65 H1N1 influenza patients during the 2009 outbreak was determined by cpn60 universal target amplification and sequencing.	The microbiota was dominated by Actinobacteria, Firmicutes and Proteobacteria including 13-20 species and diversity increasing with age.	[78]
USA	16S rRNA gene was used to identify abundant pathogens in the lungs. Only 12 out of 56 showed positive culture for the pathogen.	The results of 16s rRNA analysis were in concordance with clinically isolated pathogens among 11 positive samples. S. aureus, Pseudomonas aeruginosa, E. coli, Fusobacterium, H. influenza, Klebsiella pneumoniae, Enterococcus, Mycoplasma, Prevotella, Veillonella, Rothia, Neisseria, Streptococcus, Garanulicattella, and Gemella were found with the lung samples.	[79]
	The URT and LRT microbiota of smokers and non-smokers were analyzed through 16s rRNA among a total of 64 participants.	Generally, the same bacteria were present in the lungs and oral cavity, except Enterobacteriaceae, Haemophilus, Methylobacterium, and Ralstonia spp., those were disproportionate in lungs and oral cavity. Tropheryma was lungs specific. The oral microbiota, but not the lung microbiota varies among smokers and non-smoker.	[80]
	Lung microbiota was analyzed through BAL collected from 29 asymptomatic individuals, including 9 never, 14 formers, and 6 current smokers with the use of 16s rRNA. Pulmonary inflammation was also evaluated.	LRT microbiota was showing two groups called as pneumotypes. The first pneumotype was similar to the saline group while the second penumotype was showing a higher abundance of supraglottic-characteristic taxa. The later was called as pneumotypeSCT and consist of Veillonella and Prevotella, this was associated with increased lung inflammation.	[81]
	40 participants included in the BOBCAT asthma-related study were selected, and their airway microbiota was analyzed through 16s rRNA. The microbiota profile was matched with clinical and inflammatory features.	The microbiota dysbiosis was found to be related with the inflammatory process, and microbiota composition varies in mild to severe asthma. Preteobacteria were primarily associated with poor asthma control questionnaire (ACQ) score, while Actinobacteria were related with improved ACQ score.	[82]
Central America
Nicaragua	Participants were enrolled for household transmission study of Influenza and to understand the role of respiratory microbiota in the susceptibility to influenza virus infection.	The microbiota were divided into oligotypes, Alloprevotella sp. and Prevotella histicola/sp./veroralis/fusca/scopos/melaninogenica were positively involved in influenza virus infection. Bacteroides vulgatus oligotype was negatively associated with infection.	[83]
South America
Colombia	Respiratory samples, including, sputum, OP, and nasal samples were collected from TB patients and healthy controls in order to determine bacterial and fungal diversity.	Only OP samples were showing variability among TB and control group. Bacteroidetes, Fusobacteria, Actinobacteria, Proteobacteria were showing differences in relative abundance.	[84]
Europe
Italy	165 samples were collected as non-malignant lung tissue from cancer patients, and the microbiota profile was determined.	The Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria were forming core microbiota. At the genera level, Proteobacteria genera: Acinetobacter, Pseudomonas, Ralstonia, and other two unknown genera belonging to Comamonadacea and Oxalobacteraceae were forming core microbiota.	[85]
	BAL samples from 10 pulmonary sarcoidosis patients and 9 interstitial lung disease patients were collected and analyzed for microbiota analysis using 16s rRNA.	Microbiota was dominated by 4 phyla, and Bacteroidetes was abundant in both groups.	[86]
Netherland	25 set of samples from CF patients were involved in the study and their NP, OP, and BAL samples were collected and analyzed for microbiota using 16s rRNA.	BAL microbiota was mixed with oral and NP flora. The OP and BAL showed an abundance of commensals like Neisseria, Streptococcus, Rothia, Veillonella, Gemella and Prevotella spp., while NP and BAL samples showed an abundance of pathogen like S. aureus, H. influenzae and Moraxella. Corynebacterium and Dolosigranulum spp. were present with all NP samples.	[87]
France	16s rRNA analysis was performed to analyze the microbiota composition of 225NP samples collected from 177 viral respiratory infected patients and 48 controls.	Symptomatic respiratory infections are linked with decreased alpha diversity, loss of microbiota components, especially Prevotella spp. and increased respiratory pathogens including Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Dolosigranulum pigrum and Corynebacterium propinquum/pseudodiphtheriticum.	[35]
UK	Experimental post influenza challenged throat microbiota was analyzed using 16s rRNA from 52 experimental and 35 healthy controls.	At genera level Streptococcus, Fusobacterium and Prevotella, Neisseria, Haemophilus, and Campylobacter were abundant. Prevotella and Fusobacterium were found to varied between Influenza-Like Illness/Sflu+ and Asymptomatic control groups.	[88]
Africa
Uganda	BAL was collected from 60 HIV infected acute pneumonia patients, and microbiota was analyzed through 16s rRNA.	Rich and diverse microbiota was related to low bacteria burden. Pseudomonas aeruginosa was most prevalent in the group.	[89]
Kenya	NP microbiota of 60 children who have received PHiD-CV (n=30) or Hepatitis A vaccine was analyzed through 16s rRNA.	Moraxella catarrhalis, Streptococcus pneumoniae and Corynebacterium spp. were abundant in pre-vaccination NP microbiota, while Streptococcus, Moraxella, and Haemophilus spp. were abundant in post-vaccination NP microbiota.	[90]
South Africa, Mozambique and Morocco	Respiratory virus and bacteria were identified in acute lower respiratory infection patients using 16s rRNA.	Streptococcus was the most common bacteria, while human rhinovirus was the most common virus linked with acute lower respiratory tract infections.	[91]
Australia
Australia	NP microbiota was analyzed from persistent wheezing disease due to infection associated with lower airway inflammation patients.	Alloiococcus (11.1%), Corynebacterium (12.1%), Haemophilus (8.6%), Moraxella (40.1%), Streptococcus (13.3%), and Staphylococcus (4.2%) were abundant in microbiota.	[92]

Abbreviations: AN-anterior nares; NP-Nasopharynx; OP-Oropharynx; URT-upper respiratory; LRT-lower respiratory; ILI/S^flu+-Influenza-like illness.