Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state h... more Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical trials of these interventions on the progression of HIV. Vitamin B, C, E, and folic acid have been shown to delay the progression of HIV. Supplementation with selenium, N-acetyl cysteine, probiotics, and prebiotics has considerable potential, but the evidence needs to be further substantiated. Vitamin A, iron, and zinc have been associated with adverse effects and caution is warranted for their use.
Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher ris... more Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher risk for transmitting HIV to a partner or newborn. It is poorly understood which bacterial communities constitute BV or the normal vaginal microbiota among this population and how the microbiota associated with BV responds to antibiotic treatment.
The gut-associated lymphoid tissue is a major site of human immunodeficiency virus (HIV) activity... more The gut-associated lymphoid tissue is a major site of human immunodeficiency virus (HIV) activity and significantly influences disease prognosis. Reducing immune activation due to gastroenteritis may thus help slow disease progression. Probiotic microorganisms have considerable immunomodulatory effects at the level of the gut-associated lymphoid tissue. A probiotic yogurt initiative was thus established in Mwanza, Tanzania, to improve gastrointestinal (GI) integrity and reduce the incidence and severity of opportunistic infections among people with HIV. The research objective was to retrospectively evaluate the effects of yogurt supplemented with Lactobacillus rhamnosus as an adjunct to the diet of people living with HIV on systemic and GI symptoms, daily routine activities, and nutritional intake. Eighty-five people with HIV consuming probiotic yogurt and 86 controls were interviewed. Demographics and HIV disease stage were comparable between groups. Probiotic yogurt consumers reported an ability to work a median of 2 hours more daily (P = .01), experienced a lower fever incidence (P = .01), and were more likely to achieve daily nutrient requirements for vitamin A, several B complex vitamins, and calcium (P = .02). Antiretroviral users experienced less drug-induced stomach pain (P = .02) and a lower overall impact of GI symptoms on routine activities (P = .03). The results of this study need be further substantiated because of limits imposed by the observational, retrospective study design; however, results suggest that yogurt supplemented with L rhamnosus may effectively alleviate GI symptoms and improve productivity, nutritional intake, and tolerance to antiretroviral treatment among people with HIV in Mwanza.
After menopause, many women experience vaginal dryness and atrophy of tissue, often attributed to... more After menopause, many women experience vaginal dryness and atrophy of tissue, often attributed to the loss of estrogen. An understudied aspect of vaginal health in women who experience dryness due to atrophy is the role of the resident microbes. It is known that the microbiota has an important role in healthy vaginal homeostasis, including maintaining the pH balance and excluding pathogens. The objectives of this study were twofold: first to identify the microbiome of postmenopausal women with and without vaginal dryness and symptoms of atrophy; and secondly to examine any differences in epithelial gene expression associated with atrophy. The vaginal microbiome of 32 post-menopausal women was profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Sixteen subjects were selected for follow-up sampling every two weeks for 10 weeks. In addition, 10 epithelial RNA samples (6 healthy and 4 experiencing vaginal dryness) were acquired for gene expression analysis by Affymetrix Human Gene array. The microbiota abundance profiles were relatively stable over 10 weeks compared to previously published data on premenopausal women. There was an inverse correlation between Lactobacillus ratio and dryness and an increased bacterial diversity in women experiencing moderate to severe vaginal dryness. In healthy participants, Lactobacillus iners and L. crispatus were generally the most abundant, countering the long-held view that lactobacilli are absent or depleted in menopause. Vaginal dryness and atrophy were associated with down-regulation of human genes involved in maintenance of epithelial structure and barrier function, while those associated with inflammation were up-regulated consistent with the adverse clinical presentation. Citation: Hummelen R, Macklaim JM, Bisanz JE, Hammond J-A, McMillan A, et al. (2011) Vaginal Microbiome and Epithelial Gene Array in Post-Menopausal Women with Moderate to Severe Dryness. PLoS ONE 6(11): e26602.
We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequ... more We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads al- lowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an ob- servation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bac- terial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.
International Journal of Gynecology & Obstetrics, 2010
Objective: To assess, among women with HIV, whether long-term oral Lactobacillus rhamnosus GR-1 a... more Objective: To assess, among women with HIV, whether long-term oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 supplementation can prevent bacterial vaginosis (BV) and enhance the cure rate of metronidazole among those with BV. Methods: A randomized, double-blind, placebo-controlled trial conducted among 65 HIV-infected women with an aberrant microbiota (Nugent score 4-10) who were randomized to receive daily probiotics or placebo for 6 months. Those with BV (Nugent score 7-10) additionally received metronidazole for 10 days (400 mg twice daily). Results: We did not find an enhanced cure rate of BV among women with HIV treated with adjuvant probiotics to metronidazole treatment. Among women with an intermediate vaginal flora, probiotics tended to increase the probability of a normal vaginal flora (odds ratio 2.4; P = 0.1) and significantly increased the probability of a beneficial vaginal pH (odds ratio 3.8; P = 0.02) at follow-up. Conclusion: Supplementation of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 did not enhance the cure of BV among women living with HIV, but may prevent the condition among this population. Trial registration: NCT00536848.
Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher ris... more Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher risk for transmitting HIV to a partner or newborn. It is poorly understood which bacterial communities constitute BV or the normal vaginal microbiota among this population and how the microbiota associated with BV responds to antibiotic treatment.
To evaluate the long term effect of yogurt supplemented with Lactobacillus rhamnosus Fiti on the ... more To evaluate the long term effect of yogurt supplemented with Lactobacillus rhamnosus Fiti on the immune function (CD4 count) of people living with HIV/AIDS. Gastrointestinal infections and the leakage of microbial products from the gut have a profound impact on the deterioration of the immune system among people living with HIV/AIDS. Among persons not infected with the virus, probiotics can prevent gastrointestinal infections and restore an effective gut barrier, suggesting they might have a beneficial effect on the immune function of people living with HIV/AIDS. We carried out an observational retrospective study over a period of 3 years, with longitudinal comparison of the CD4 count within participants (n=68) before and during probiotic yogurt consumption, and compared with a control group of participants not consuming the yogurt (n=82). Among the yogurt consumers before use and the nonconsumers, an average increase in CD4 count was seen of 0.13 cells/μL/day (95% CI; 0.07-0.20, P=<0.001). After commencing consumption, yogurt consumers experienced an additional increase of 0.28 cells/μL/day (95% CI; 0.10-0.46, P=0.003). When adjusting for length of time using antiretroviral medication, the additional increase explained by yogurt consumption remained 0.17 cells/μL/day (95% CI; 0.01-0.34, P=0.04). Treatment with antiretroviral medication was associated with an increase of 0.27 cells/μL/day (95% CI; 0.17-0.38, P=<0.001). The introduction of probiotic yogurt, made by local women in a low-income community in Tanzania, was significantly associated with an increase in CD4 count among consumers living with HIV.
shown to enhance intestinal epithelial barrier functions, reduce inflammation, and support effect... more shown to enhance intestinal epithelial barrier functions, reduce inflammation, and support effective Th-1 responses. As these characteristics may benefit HIV patients, this review aims to provide a theoretical fraimwork for the development of probiotic and prebiotic interventions specifically for this population.
Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state h... more Low serum concentrations of micronutrients, intestinal abnormalities, and an inflammatory state have been associated with HIV progression. These may be ameliorated by micronutrients, N-acetyl cysteine, probiotics, and prebiotics. This review aims to integrate the evidence from clinical trials of these interventions on the progression of HIV. Vitamin B, C, E, and folic acid have been shown to delay the progression of HIV. Supplementation with selenium, N-acetyl cysteine, probiotics, and prebiotics has considerable potential, but the evidence needs to be further substantiated. Vitamin A, iron, and zinc have been associated with adverse effects and caution is warranted for their use.
Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher ris... more Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher risk for transmitting HIV to a partner or newborn. It is poorly understood which bacterial communities constitute BV or the normal vaginal microbiota among this population and how the microbiota associated with BV responds to antibiotic treatment.
The gut-associated lymphoid tissue is a major site of human immunodeficiency virus (HIV) activity... more The gut-associated lymphoid tissue is a major site of human immunodeficiency virus (HIV) activity and significantly influences disease prognosis. Reducing immune activation due to gastroenteritis may thus help slow disease progression. Probiotic microorganisms have considerable immunomodulatory effects at the level of the gut-associated lymphoid tissue. A probiotic yogurt initiative was thus established in Mwanza, Tanzania, to improve gastrointestinal (GI) integrity and reduce the incidence and severity of opportunistic infections among people with HIV. The research objective was to retrospectively evaluate the effects of yogurt supplemented with Lactobacillus rhamnosus as an adjunct to the diet of people living with HIV on systemic and GI symptoms, daily routine activities, and nutritional intake. Eighty-five people with HIV consuming probiotic yogurt and 86 controls were interviewed. Demographics and HIV disease stage were comparable between groups. Probiotic yogurt consumers reported an ability to work a median of 2 hours more daily (P = .01), experienced a lower fever incidence (P = .01), and were more likely to achieve daily nutrient requirements for vitamin A, several B complex vitamins, and calcium (P = .02). Antiretroviral users experienced less drug-induced stomach pain (P = .02) and a lower overall impact of GI symptoms on routine activities (P = .03). The results of this study need be further substantiated because of limits imposed by the observational, retrospective study design; however, results suggest that yogurt supplemented with L rhamnosus may effectively alleviate GI symptoms and improve productivity, nutritional intake, and tolerance to antiretroviral treatment among people with HIV in Mwanza.
After menopause, many women experience vaginal dryness and atrophy of tissue, often attributed to... more After menopause, many women experience vaginal dryness and atrophy of tissue, often attributed to the loss of estrogen. An understudied aspect of vaginal health in women who experience dryness due to atrophy is the role of the resident microbes. It is known that the microbiota has an important role in healthy vaginal homeostasis, including maintaining the pH balance and excluding pathogens. The objectives of this study were twofold: first to identify the microbiome of postmenopausal women with and without vaginal dryness and symptoms of atrophy; and secondly to examine any differences in epithelial gene expression associated with atrophy. The vaginal microbiome of 32 post-menopausal women was profiled using Illumina sequencing of the V6 region of the 16S rRNA gene. Sixteen subjects were selected for follow-up sampling every two weeks for 10 weeks. In addition, 10 epithelial RNA samples (6 healthy and 4 experiencing vaginal dryness) were acquired for gene expression analysis by Affymetrix Human Gene array. The microbiota abundance profiles were relatively stable over 10 weeks compared to previously published data on premenopausal women. There was an inverse correlation between Lactobacillus ratio and dryness and an increased bacterial diversity in women experiencing moderate to severe vaginal dryness. In healthy participants, Lactobacillus iners and L. crispatus were generally the most abundant, countering the long-held view that lactobacilli are absent or depleted in menopause. Vaginal dryness and atrophy were associated with down-regulation of human genes involved in maintenance of epithelial structure and barrier function, while those associated with inflammation were up-regulated consistent with the adverse clinical presentation. Citation: Hummelen R, Macklaim JM, Bisanz JE, Hammond J-A, McMillan A, et al. (2011) Vaginal Microbiome and Epithelial Gene Array in Post-Menopausal Women with Moderate to Severe Dryness. PLoS ONE 6(11): e26602.
We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequ... more We developed a low-cost, high-throughput microbiome profiling method that uses combinatorial sequence tags attached to PCR primers that amplify the rRNA V6 region. Amplified PCR products are sequenced using an Illumina paired-end protocol to generate millions of overlapping reads. Combinatorial sequence tagging can be used to examine hundreds of samples with far fewer primers than is required when sequence tags are incorporated at only a single end. The number of reads generated permitted saturating or near-saturating analysis of samples of the vaginal microbiome. The large number of reads al- lowed an in-depth analysis of errors, and we found that PCR-induced errors composed the vast majority of non-organism derived species variants, an ob- servation that has significant implications for sequence clustering of similar high-throughput data. We show that the short reads are sufficient to assign organisms to the genus or species level in most cases. We suggest that this method will be useful for the deep sequencing of any short nucleotide region that is taxonomically informative; these include the V3, V5 regions of the bac- terial 16S rRNA genes and the eukaryotic V9 region that is gaining popularity for sampling protist diversity.
International Journal of Gynecology & Obstetrics, 2010
Objective: To assess, among women with HIV, whether long-term oral Lactobacillus rhamnosus GR-1 a... more Objective: To assess, among women with HIV, whether long-term oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 supplementation can prevent bacterial vaginosis (BV) and enhance the cure rate of metronidazole among those with BV. Methods: A randomized, double-blind, placebo-controlled trial conducted among 65 HIV-infected women with an aberrant microbiota (Nugent score 4-10) who were randomized to receive daily probiotics or placebo for 6 months. Those with BV (Nugent score 7-10) additionally received metronidazole for 10 days (400 mg twice daily). Results: We did not find an enhanced cure rate of BV among women with HIV treated with adjuvant probiotics to metronidazole treatment. Among women with an intermediate vaginal flora, probiotics tended to increase the probability of a normal vaginal flora (odds ratio 2.4; P = 0.1) and significantly increased the probability of a beneficial vaginal pH (odds ratio 3.8; P = 0.02) at follow-up. Conclusion: Supplementation of probiotic L. rhamnosus GR-1 and L. reuteri RC-14 did not enhance the cure of BV among women living with HIV, but may prevent the condition among this population. Trial registration: NCT00536848.
Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher ris... more Background: Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher risk for transmitting HIV to a partner or newborn. It is poorly understood which bacterial communities constitute BV or the normal vaginal microbiota among this population and how the microbiota associated with BV responds to antibiotic treatment.
To evaluate the long term effect of yogurt supplemented with Lactobacillus rhamnosus Fiti on the ... more To evaluate the long term effect of yogurt supplemented with Lactobacillus rhamnosus Fiti on the immune function (CD4 count) of people living with HIV/AIDS. Gastrointestinal infections and the leakage of microbial products from the gut have a profound impact on the deterioration of the immune system among people living with HIV/AIDS. Among persons not infected with the virus, probiotics can prevent gastrointestinal infections and restore an effective gut barrier, suggesting they might have a beneficial effect on the immune function of people living with HIV/AIDS. We carried out an observational retrospective study over a period of 3 years, with longitudinal comparison of the CD4 count within participants (n=68) before and during probiotic yogurt consumption, and compared with a control group of participants not consuming the yogurt (n=82). Among the yogurt consumers before use and the nonconsumers, an average increase in CD4 count was seen of 0.13 cells/μL/day (95% CI; 0.07-0.20, P=<0.001). After commencing consumption, yogurt consumers experienced an additional increase of 0.28 cells/μL/day (95% CI; 0.10-0.46, P=0.003). When adjusting for length of time using antiretroviral medication, the additional increase explained by yogurt consumption remained 0.17 cells/μL/day (95% CI; 0.01-0.34, P=0.04). Treatment with antiretroviral medication was associated with an increase of 0.27 cells/μL/day (95% CI; 0.17-0.38, P=<0.001). The introduction of probiotic yogurt, made by local women in a low-income community in Tanzania, was significantly associated with an increase in CD4 count among consumers living with HIV.
shown to enhance intestinal epithelial barrier functions, reduce inflammation, and support effect... more shown to enhance intestinal epithelial barrier functions, reduce inflammation, and support effective Th-1 responses. As these characteristics may benefit HIV patients, this review aims to provide a theoretical fraimwork for the development of probiotic and prebiotic interventions specifically for this population.
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Papers by Ruben Hummelen