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Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine.

ABSTRACT: Some intestinal microbiota-generated metabolites of phosphatidylcholine are recognized to be proatherogenic. As the HIV population is vulnerable to cardiovascular disease and can develop intestinal dysbiosis associated with systemic inflammation, we investigated the novel relationship between microbiota-derived metabolites of phosphatidylcholine and coronary atherosclerosis in HIV.One hundred and fifty-five HIV-infected and 67 non-HIV-infected individuals without known history of cardiovascular disease were previously recruited to assess coronary plaque by computed tomography angiography. In the current study, we evaluate whether serum choline, trimethylamine (TMA), or trimethylamine-N-oxide (TMAO) levels are associated with plaque features.Young, asymptomatic HIV-infected patients (age 47?±?7 years) demonstrated significantly higher prevalence of plaque (53 vs. 35%, P?=?0.01) and number of total plaque segments (1.8?±?2.5 vs. 1.2?±?2.2, P?=?0.03) when compared with well matched noninfected individuals with similar comorbidities. TMA was significantly associated with calcium score (r?=?0.22, P?=?0.006), number of total (r?=?0.20, P?=?0.02) and calcified (r?=?0.18, P?=?0.03) plaque segments, and calcium plaque volume (r?=?0.19, P?=?0.02) and mass (r?=?0.22, P?=?0.009) in the HIV cohort only. In multivariate modeling among HIV-infected patients, TMA remained significantly associated with calcium score (P?=?0.008), number of total (P?=?0.005) and calcified (P?=?0.02) plaque segments, and calcium plaque volume (P?=?0.01) and mass (P?=?0.007), independent of Framingham risk score. In contrast, there was no association of TMAO to coronary plaque features in either cohort.A link between TMA and atherosclerosis has not previously been established. The current study suggests that TMA may be a nontraditional risk factor related to the number of plaque segments and severity of calcified plaque burden in HIV.

SUBMITTER: Srinivasa S

PROVIDER: S-EPMC4410017 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine.

Srinivasa Suman S Fitch Kathleen V KV Lo Janet J Kadar Hanane H Knight Rachel R Wong Kimberly K Abbara Suhny S Gauguier Dominique D Capeau Jacqueline J Boccara Franck F Grinspoon Steven K SK

AIDS (London, England) 20150201 4

<h4>Objective</h4>Some intestinal microbiota-generated metabolites of phosphatidylcholine are recognized to be proatherogenic. As the HIV population is vulnerable to cardiovascular disease and can develop intestinal dysbiosis associated with systemic inflammation, we investigated the novel relationship between microbiota-derived metabolites of phosphatidylcholine and coronary atherosclerosis in HIV.<h4>Design/methods</h4>One hundred and fifty-five HIV-infected and 67 non-HIV-infected individuals ...[more]

PMID: 25565500

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Project description:BackgroundIntestinal inflammation and periodontitis influence the development of each other through the bidirectional relationship. As the intestinal microbiome metabolite, trimethylamine-N-oxide (TMAO) could contribute to chronic inflammation in the gut by influencing the gut microbial composition and intestinal immunity. Increased circulating TMAO levels often accompany clinical findings in patients with experimental periodontitis. However, the role of TMAO in the bidirectional relationship between intestinal inflammation and periodontitis remains unclear. Thus, we explored whether TMAO influences the periodontitis process by affecting intestinal immunity and microbial composition in this article.MethodsPeriodontitis was induced by unilateral ligation of the first molar in mice, and 3,3-dimethyl-1-butanol (DMB) was used as an inhibitor to reduce TMAO circulating. Twenty-five BALB/c mice were randomly assigned to five study sets (n = 5/group): no periodontitis with DMB (Control group), periodontitis (P) group, periodontitis with TMAO (P+TMAO) group, periodontitis with TMAO and DMB (P+TMAO+DMB) group, and periodontitis with DMB (P+DMB) group. The effect of TMAO was determined by assessing changes in intestinal histology, intestinal flora composition, periodontal tissue, and periodontal pro-inflammatory factors at ten days.ResultsThe outcomes indicated a marked improvement in the intestinal inflammation severity, and intestinal flora diversity was reduced. Firmicutes number and the ratio of Firmicutes/Bacteroidetes were improved in the P+TMAO group. In addition, the alveolar bone resorption and the degree of periodontal tissue inflammation were more severe in the P+TMAO group than in other groups. Immunohistochemistry showed higher levels of TGF-β and IL-1β expression in the periodontal tissues of P+TMAO.ConclusionsOur data suggest that TMAO could influence periodontal immunity and promote periodontal inflammation by affecting the intestinal microenvironment, revealing TMAO may affect the development of periodontitis through the bidirectional relationship of the oral-gut axis.

Project description:UnlabelledCholine is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans.ImportanceCardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases.

Dataset Information

Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine.

Publications

Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine.

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