Paper of the month
This section will be a summary of some of my favourite papers I read each month.
April 2023
The gut microbiome and early-life growth in a population with high prevalence of stunting.
This study investigates the early-life gut microbiome (1 month to 18 months) of 335 children from rural Zimbabwe where there is high prevalence of stunted growth. They hypothesise that "randomised nutrition and hygiene interventions would alter gut microbiome development and that gut microbiome composition and function could predict child growth." They also investigate if these interventions can improve linear growth (increase in height) as well as the effect of maternal HIV status on the infant gut microbiome.
Using powerful XGBoost machine learning approaches, they found that the gut microbiome composition and function in early childhood were most defined by age of the child. Additionally, they determined that maternal HIV status also defined the infant gut microbiome composition and functionality with infants born to mothers living with HIV having decreased abundance of Bifidobacteria, decreased amino acid biosynthesis pathways and increased sugar degradation pathways. However, the functionality of the gut microbiome, not composition, was the best predictor of both linear and ponderal (body weight: length ratio). Vitamin B biosynthesis, purine, pyrimidine, carbohydrate degradation and lipid biosynthesis pathways were the most predictive pathways for linear growth and metagenomic amino acid, nucleotide and O-antigen biosynthesis pathways being predictive for ponderal growth.
However, the hygiene and nutrition interventions had little to no effect on infant gut microbiome. Therefore, therapeutics targeting the gut microbiome might alleviate poor clinical outcomes for children in these populations.
This study investigates the early-life gut microbiome (1 month to 18 months) of 335 children from rural Zimbabwe where there is high prevalence of stunted growth. They hypothesise that "randomised nutrition and hygiene interventions would alter gut microbiome development and that gut microbiome composition and function could predict child growth." They also investigate if these interventions can improve linear growth (increase in height) as well as the effect of maternal HIV status on the infant gut microbiome.
Using powerful XGBoost machine learning approaches, they found that the gut microbiome composition and function in early childhood were most defined by age of the child. Additionally, they determined that maternal HIV status also defined the infant gut microbiome composition and functionality with infants born to mothers living with HIV having decreased abundance of Bifidobacteria, decreased amino acid biosynthesis pathways and increased sugar degradation pathways. However, the functionality of the gut microbiome, not composition, was the best predictor of both linear and ponderal (body weight: length ratio). Vitamin B biosynthesis, purine, pyrimidine, carbohydrate degradation and lipid biosynthesis pathways were the most predictive pathways for linear growth and metagenomic amino acid, nucleotide and O-antigen biosynthesis pathways being predictive for ponderal growth.
However, the hygiene and nutrition interventions had little to no effect on infant gut microbiome. Therefore, therapeutics targeting the gut microbiome might alleviate poor clinical outcomes for children in these populations.
March 2023
HIV- associated vaginal microbiome and inflammation predict spontaneous preterm (sPTB) birth in Zambia
This study investigates whether the vaginal microbiome and local immune response of pregnant people with or without HIV are correlated with sPTB. They hypothesise that "the elevated risk of preterm delivery faced by women with HIV may be related to measurable differences in the vaginal microbial and immune milieu during pregnancy". The objective of this study was to understand the biological processes by which HIV infection modulates sPTB as this can inform the development of effective therapies for the prevention of HIV-related obstetric outcomes.
In 99% of the samples, the most common bacteria taxa was all subspecies of Gardnerella genus . They identified two distinct metagenomic subspecies within the Gardnerella genus which were : type 1 = high proportion of G.swidsinkii/G.leopoldi type 2 = diverse array of Gardnerella spp. and other = low overall relative abundance of Gardnerella spp. Based on all the samples, they clustered the vaginal microbiome based on similar composition and abundance into 7 metagenomic clusters (mgClust) namely: mgClust1 was dominated by L. iners , mgClust2 by a mix of L. iners and Gardnerella “other”; mgClust3 by Gardnerella type 1 ; mgClust4 by P. bivia, A. vaginae, and Gardnerella (a mix of all three metagenomic subspecies), mgClust5 by L. iners, Gardnerella type 2, and Ca. Lachnocurva vaginae; and mgClust6 by Gardnerella type 2, L. iners, and P. bivia. Finally, mgClust7 comprised predominantly L. crispatus (86%) with minor co-occurrence of other Lactobacilli.
mgClust1 was the most common in people without HIV (HIV -ve) and people living with HIV (HIV +ve) with a low viral load. Whereas, mgCLust6 was the most common in people living with HIV with a high viral load. They also found that vaginal inflammation in all participants at baseline and an increase in microbial diversity through pregnancy among a subset of people living with HIV were associated with sPTB. They posit that a Lactobacillus-deficient vaginal microbiome might explain this increased risk of sPTB as seen in other studies.
This study investigates whether the vaginal microbiome and local immune response of pregnant people with or without HIV are correlated with sPTB. They hypothesise that "the elevated risk of preterm delivery faced by women with HIV may be related to measurable differences in the vaginal microbial and immune milieu during pregnancy". The objective of this study was to understand the biological processes by which HIV infection modulates sPTB as this can inform the development of effective therapies for the prevention of HIV-related obstetric outcomes.
In 99% of the samples, the most common bacteria taxa was all subspecies of Gardnerella genus . They identified two distinct metagenomic subspecies within the Gardnerella genus which were : type 1 = high proportion of G.swidsinkii/G.leopoldi type 2 = diverse array of Gardnerella spp. and other = low overall relative abundance of Gardnerella spp. Based on all the samples, they clustered the vaginal microbiome based on similar composition and abundance into 7 metagenomic clusters (mgClust) namely: mgClust1 was dominated by L. iners , mgClust2 by a mix of L. iners and Gardnerella “other”; mgClust3 by Gardnerella type 1 ; mgClust4 by P. bivia, A. vaginae, and Gardnerella (a mix of all three metagenomic subspecies), mgClust5 by L. iners, Gardnerella type 2, and Ca. Lachnocurva vaginae; and mgClust6 by Gardnerella type 2, L. iners, and P. bivia. Finally, mgClust7 comprised predominantly L. crispatus (86%) with minor co-occurrence of other Lactobacilli.
mgClust1 was the most common in people without HIV (HIV -ve) and people living with HIV (HIV +ve) with a low viral load. Whereas, mgCLust6 was the most common in people living with HIV with a high viral load. They also found that vaginal inflammation in all participants at baseline and an increase in microbial diversity through pregnancy among a subset of people living with HIV were associated with sPTB. They posit that a Lactobacillus-deficient vaginal microbiome might explain this increased risk of sPTB as seen in other studies.
February 2023
Spinal cord injury changes the structure and functional potential of gut bacterial and viral communities
This study explores the effects of different levels of spinal cord injury (SCI) on the gut microbiome and virome in mice. Understanding these changes can aid in the development of therapies, such as faecal microbiota transplantation or phage therapy, to improve outcomes for people with SCI. While there have been some previous studies on how the gut microbiome is impacted after SCI in both humans and mouse models, this is the first study that used metagenomics, providing better taxonomic resolution and functional insight.
The study found that SCI at the T4 and T10 levels decreased the abundance of commensal bacteria, allowing pathogenic bacteria to establish niches and resulting in a decrease or loss of beneficial microbial functions. For instance, the loss or decrease of the commensal Lactobacillus johnsonii resulted in a reduction of lactocepin, which selectively degrades proinflammatory chemokines and exerts anti-inflammatory effects. T4 spinal injuries showed greater distinct changes in the gut microbiota than Lam/sham controls, while T10 spinal injuries also showed changes in the gut microbiota, but not as pronounced as T4 changes.
Additionally, the gut virome was altered after SCI, particularly at the higher level (T4) injury, impacting both the temperate and lytic phages. The study also found an increase in the abundance of viral genes related to stress response and a decrease in genes related to host immune response.
This study explores the effects of different levels of spinal cord injury (SCI) on the gut microbiome and virome in mice. Understanding these changes can aid in the development of therapies, such as faecal microbiota transplantation or phage therapy, to improve outcomes for people with SCI. While there have been some previous studies on how the gut microbiome is impacted after SCI in both humans and mouse models, this is the first study that used metagenomics, providing better taxonomic resolution and functional insight.
The study found that SCI at the T4 and T10 levels decreased the abundance of commensal bacteria, allowing pathogenic bacteria to establish niches and resulting in a decrease or loss of beneficial microbial functions. For instance, the loss or decrease of the commensal Lactobacillus johnsonii resulted in a reduction of lactocepin, which selectively degrades proinflammatory chemokines and exerts anti-inflammatory effects. T4 spinal injuries showed greater distinct changes in the gut microbiota than Lam/sham controls, while T10 spinal injuries also showed changes in the gut microbiota, but not as pronounced as T4 changes.
Additionally, the gut virome was altered after SCI, particularly at the higher level (T4) injury, impacting both the temperate and lytic phages. The study also found an increase in the abundance of viral genes related to stress response and a decrease in genes related to host immune response.
January 2023
Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women
This longitudinal study follows HIV-uninfected 18-23yo women in SA to understand how their vaginal microbiome is linked with HIV acquisition. They found that SA women have a distinct bacterial (not viral) cervicovaginal communities. The bacterial communities were clustered into 4 distinct groups called cervicotypes (CTs). CT1 is dominated by L. crispatus and has low diversity. This CT is comparable to CST1 described in western cohorts. CT2 is dominated by L. iners , also low diversity and is similar to CST3 in western cohorts. CT3 is high diversity and dominated by G. vaginalis and CT4 is also high diversity but dominated by any other species that are not Lactobacilli or Gardnerella. The last two CTs are more like CST4 and have more anaerobic bacteria. They were also able to identify multiple phages from the Caudovirales order as well as Alphapapillomaviruses & Anelloviridae as the dominant eukaryotic viruses. There were no discernable differences in viral communities between individuals.
Participants with CT3 and CT4 had a higher incidence of HIV acquisition compared to 1 and 2. In fact, none of the women in CT1/2 acquired HIV. Additionally, they saw that women with a more anaerobic vaginal microbiota (CT3/4?) had increased activated CD4+ cells as well as high levels of pro-inflammatory cytokines.
L. crispatus was associated with reduced inflammation and HIV acquisition whereas Prevotella & Snethia were associated with increased inflammation and HIV acquisition. When the genital tract of germ free mice was inoculated with these anerobic bacteria ( G. vaginalis, P. bivia, P amnii with L. crispatus as the 'good guy'), they saw that in mice with G. vaginalis, P. bivia, P amnii there was an increase in pro-inflammatory cytokines and higher CD4+ cell count.
This longitudinal study follows HIV-uninfected 18-23yo women in SA to understand how their vaginal microbiome is linked with HIV acquisition. They found that SA women have a distinct bacterial (not viral) cervicovaginal communities. The bacterial communities were clustered into 4 distinct groups called cervicotypes (CTs). CT1 is dominated by L. crispatus and has low diversity. This CT is comparable to CST1 described in western cohorts. CT2 is dominated by L. iners , also low diversity and is similar to CST3 in western cohorts. CT3 is high diversity and dominated by G. vaginalis and CT4 is also high diversity but dominated by any other species that are not Lactobacilli or Gardnerella. The last two CTs are more like CST4 and have more anaerobic bacteria. They were also able to identify multiple phages from the Caudovirales order as well as Alphapapillomaviruses & Anelloviridae as the dominant eukaryotic viruses. There were no discernable differences in viral communities between individuals.
Participants with CT3 and CT4 had a higher incidence of HIV acquisition compared to 1 and 2. In fact, none of the women in CT1/2 acquired HIV. Additionally, they saw that women with a more anaerobic vaginal microbiota (CT3/4?) had increased activated CD4+ cells as well as high levels of pro-inflammatory cytokines.
L. crispatus was associated with reduced inflammation and HIV acquisition whereas Prevotella & Snethia were associated with increased inflammation and HIV acquisition. When the genital tract of germ free mice was inoculated with these anerobic bacteria ( G. vaginalis, P. bivia, P amnii with L. crispatus as the 'good guy'), they saw that in mice with G. vaginalis, P. bivia, P amnii there was an increase in pro-inflammatory cytokines and higher CD4+ cell count.
